Physician Reasons for or Against Treatment Intensification in Patients With Metastatic Prostate Cancer

Neeraj Agarwal; Daniel J George; Zachary Klaassen; Rickard Sandin; Jake Butcher; Amanda Ribbands; Liane Gillespie-Akar; Birol Emir; David Russell; Agnes Hong; Krishnan Ramaswamy; Stephen J Freedland

doi:10.1001/jamanetworkopen.2024.48707

. 2024 Dec 9;7(12):e2448707. doi: 10.1001/jamanetworkopen.2024.48707

Physician Reasons for or Against Treatment Intensification in Patients With Metastatic Prostate Cancer

Neeraj Agarwal ^1,^✉, Daniel J George ², Zachary Klaassen ³, Rickard Sandin ⁴, Jake Butcher ⁵, Amanda Ribbands ⁵, Liane Gillespie-Akar ⁵, Birol Emir ⁶, David Russell ⁶, Agnes Hong ⁶, Krishnan Ramaswamy ⁶, Stephen J Freedland ^7,⁸

¹Huntsman Cancer Institute, University of Utah, Salt Lake City

²Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina

³Department of Urology, Wellstar MCG Health, Augusta, Georgia

⁴Pfizer AB, Stockholm, Sweden

⁵Adelphi Real World, Bollington, Cheshire, United Kingdom

⁶Pfizer Inc, New York, New York

⁷Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California

⁸Durham Veterans Affairs Health Care System, Durham, North Carolina

Accepted for Publication: October 8, 2024.

Published: December 9, 2024. doi:10.1001/jamanetworkopen.2024.48707

^✉

Corresponding Author: Neeraj Agarwal, MD, Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Dr, Salt Lake City, UT 84112 (neeraj.agarwal@hci.utah.edu).

Author Contributions: Dr Agarwal and Mr Butcher had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Agarwal, George, Sandin, Butcher, Ribbands, Emir, Russell, Hong, Ramaswamy, Freedland.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Agarwal, Sandin, Butcher, Emir, Hong, Ramaswamy, Freedland.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Sandin, Butcher, Gillespie-Akar, Emir, Hong, Ramaswamy.

Obtained funding: Ramaswamy.

Administrative, technical, or material support: Agarwal, Butcher, Emir.

Supervision: Agarwal, Klaassen, Sandin, Ribbands, Emir, Ramaswamy, Freedland.

Conflict of Interest Disclosures: Dr Agarwal reported receiving honoraria before May 2021 and during his lifetime for consulting from Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics and receiving research funding (to the institution) from Arnivas, Astellas, AstraZeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, CRISPR Therapeutics, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. Dr George reported receiving personal fees from ABRX, AstraZeneca, AVEO, Bayer, Eisai, Exelixis, IdeOncology, Janssen, Merck, MJH Associates, Nektar, Pfizer, Propella TX, Sanofi, Seattle Genetics, Sumitovant Biopharma, Surface Oncology, UroGPO, UroToday, and WebMD and receiving grants from Astellas, AstraZeneca, BMS, CORVUS, Exelixis, Janssen Pharma, Novartis, Pfizer, and Surface Oncology outside the submitted work. Dr Klaassen reported receiving personal fees from Astellas/Pfizer, Bayer, and Novartis during the conduct of the study. Dr Sandin reported having stock options in Pfizer outside the submitted work. Mr Butcher and Mss Ribbands and Gillespie-Akar reported receiving fees from Pfizer for a subscription to the Prostate Cancer Wave IV Disease Specific Programme (DSP) during the conduct of the study and having a patent for the DSP licensed to Adelphi Real World (ARW). Dr Emir, Dr Russell, and Ms Hong reported having stock options in Pfizer outside the submitted work. Dr Ramaswamy reported having stock options in Pfizer and Johnson & Johnson outside the submitted work. Dr Freedland reported receiving personal fees from Pfizer and Astellas during the conduct of the study and receiving personal fees from Astellas, Bayer, Pfizer, Sanofi, Merck, AstraZeneca, Eli Lilly, Novartis, and Janssen outside the submitted work.

Funding/Support: This study was sponsored by Pfizer and Astellas Pharma, the codevelopers of enzalutamide. Data collection was undertaken by ARW as part of an independent survey, entitled the Adelphi Real World mCSPC Retrospective Survey, a wholly owned ARW product in which Pfizer is 1 of multiple subscribers.

Role of the Funder/Sponsor: The sponsors were not involved in the design and conduct of the survey or in collection and management of the study data. The sponsors were involved in the study design, analysis, and interpretation of the data as well as the preparation and review of the manuscript. Approval of the final manuscript and the decision to submit the manuscript for publication were made by all authors and were not contingent on the sponsors’ approval.

Data Sharing Statement: See Supplement 2.

Additional Contributions: We thank everyone involved in this study. Medical writing support was provided by Kirstie Anderson, BSc; Megan Christian, MBiolSci; and Allison Alwan Terbush, PhD, and editorial support was provided by Rosie Henderson, MSc, all of Onyx (a division of Prime), which was funded by the sponsors.

^✉

Corresponding author.

PMCID: PMC11629128 PMID: 39652349

Key Points

Question

What are physicians’ beliefs about treatment intensification (TI) in metastatic castration-sensitive prostate cancer (mCSPC), and what explains the gap between guidelines and clinical practice?

Findings

In this survey study analyzing data from a survey of 107 US-based physicians, 69.7% of the 617 total adult patients did not receive first-line TI in mCSPC. Patients whose physicians chose treatment based on guidelines were significantly more likely to receive TI than patients whose physicians did not report these reasons.

Meaning

The findings of this study suggest that physician education on treatment guidelines, efficacy and safety data, and appropriate prostate-specific antigen goals may increase first-line TI use in mCSPC and may improve survival outcomes.

This survey study examines physicians’ beliefs about treatment intensification for patients with metastatic castration-sensitive prostate cancer and the gap between guidelines and clinical practice.

Abstract

Importance

Clarifying the underutilization of treatment intensification (TI) for metastatic castration-sensitive prostate cancer (mCSPC) may improve implementation of evidence-based medicine and survival outcomes.

Objective

To investigate physicians’ beliefs about TI in mCSPC to understand the gap between evidence-based guidelines and clinical practice.

Design, Setting, and Participants

This survey study analyzed data from the Adelphi Real World retrospective survey, which comprised physician surveys that were linked to medical record reviews of US adult patients treated for mCSPC between July 2018 and January 2022.

Main Outcomes and Measures

The survey included questions on physician and practice demographics. Physicians completed patient record forms, based on patient medical records with information including patient demographics, clinical characteristics, and patient management. Physicians recalled reasons for prescribing decisions using 48 precoded and open-text responses. Bivariate and multivariable analyses assessed the likelihood of their patients receiving first-line TI; the main outcome was the likelihood of their patients receiving TI using odds ratios (ORs).

Results

In total, 617 male patients met the analysis criteria (mean [SD] age, 68.6 [8.1] years). Among these patients, 349 (56.6%) were Medicare beneficiaries. Overall, 430 (69.7%) did not receive first-line TI with androgen receptor pathway inhibitors and/or chemotherapy. The 107 US-based physicians’ top reasons for treatment choice for their patients were tolerability concerns (TI: 121 [64.7%]; no TI: 252 [58.6%]; P = .18) and following guideline recommendations (TI: 115 [61.5%]; no TI: 230 [53.5%]; P = .08). In the bivariate analysis, physicians seeking to reduce prostate-specific antigen (PSA) by 75% to 100% were more likely to provide first-line TI compared with physicians who aimed to lower PSA by 0% to 49% (OR, 1.63 [95% CI, 1.04-2.56]; P = .03). In the multivariable analysis, patients whose physicians based treatment choice on guidelines were more likely to receive TI than patients whose physicians did not report this reason (OR, 3.46 [95% CI, 1.32-9.08]; P = .01).

Conclusions and Relevance

The findings of this study, which analyzed data from a medical records–linked clinical practice survey, indicated low rates of first-line TI for mCSPC despite guideline recommendations. Barriers to TI included lack of knowledge about guidelines and published efficacy and safety data. Physicians with greater PSA reduction goals were more likely to use TI. Physician education on treatment guidelines and clinical trial data, while raising expectations for PSA response, may increase rates of first-line TI in mCSPC.

Introduction

Clinical trials have demonstrated that treatment intensification (TI)—the addition of an androgen receptor pathway inhibitor (ARPI [enzalutamide, apalutamide, abiraterone, or darolutamide]), chemotherapy, or both to androgen deprivation therapy (ADT)—improves survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC).^{1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17} Guidelines, therefore, uniformly recommend TI in patients with mCSPC.^18,19,20,21 Most data from US claims-based studies were collected prior to or shortly after guidelines were updated and suggest that most patients with mCSPC do not receive TI.^{22,23,24,25,26,27,28,29,30,31,32,33} One US medical record study found that many patients (39%) with mCSPC treated in 2019 and 2020 did not receive TI.³⁴ Similarly, data from a point-in-time (January-August 2020) retrospective survey showed that 47% of patients globally (36% in the US) did not receive TI as initial treatment for mCSPC.³⁵ In that study, physicians prescribed TI to younger patients who were able to tolerate more aggressive treatment with the goal of extending life³⁵ and reserved a non-TI approach for older patients with compliance or concerns about adverse effects, with maintaining quality of life (QOL) as the main goal. From a patient perspective, results from a discrete-choice experiment of 550 patients with mCSPC across the US, the UK, and Canada suggest that efficacy is the most important factor underlying treatment choice.³⁶

We hypothesized that reasons for low use of TI may include patient characteristics, physician perception, experience with different treatments, an understanding of guidelines, treatment goals, and access or reimbursement. Greater understanding of these reasons is required to identify barriers to guideline-concordant TI, with the goal of improving survival outcomes. Our analysis investigated US-based physicians’ reasons about the use, or lack thereof, of TI in patients with mCSPC. Data were analyzed from an Adelphi Real World (ARW) retrospective mCSPC survey comprising a physician survey linked to patient medical record reviews. A key component of our analysis was to explore physician-reported reasons for patient-specific treatment choice.

Methods

Data Source

In this survey study, data were analyzed from an ARW retrospective mCSPC survey that included questions on physician and practice demographics. US-based physicians retrospectively reviewed medical records for their most recent eligible patients treated for mCSPC between July 2018 and January 2022 and completed electronic patient record forms comprising information on patient characteristics, clinical characteristics, and patient management, including treatment history. Physicians provided written informed consent using a check box acknowledging participation. All data were deidentified and aggregated before receipt and analysis by ARW. Data collection was consistent with the European Pharmaceutical Market Research Association guidelines³⁷ and, as such, did not require ethics committee approval. The survey materials were submitted to the Pearl International Review Board and following review were deemed to be exempt.³⁷ The survey was performed in full accordance with relevant legislation at the time of data collection, including the US Health Insurance Portability and Accountability Act 1996³⁸ and the Health Information Technology for Economic and Clinical Health Act legislation.³⁹

Patients’ race and ethnicity, classified into precoded categories, are based on electronic medical records in which race and ethnicity were reported as provided by physicians. The provided categories were African American, Hispanic or Latino, White or Caucasian, and other (including Asian [Indian subcontinent], Asian [other], Middle Eastern, mixed race, Native American, or Southeast Asian). Race and ethnicity were included in the study to assess the association of these variables with the likelihood of receiving TI. Physicians recorded the treatment received by the patient (TI included ADT and an ARPI; ADT and chemotherapy; or ADT, an ARPI, and chemotherapy; no TI included ADT or ADT and a first-generation nonsteroidal antiandrogen) and then recalled reasons for prescribing decisions using a precoded, 48-item list and open-text responses designed for the survey (physicians could provide multiple reasons). The eFigure in Supplement 1 shows the data-collection method. If patients did not receive an ARPI and were not prescribed any subsequent lines of treatment, physicians were asked to record the reason for not prescribing an ARPI using a separate 42-item, precoded list.

ARW Survey Inclusion Criteria

Physicians were identified by local fieldwork agents using physician panels and publicly available lists. They were invited to participate if they specialized in medical oncology or urology, had personal responsibility for prescribing decisions for patients with mCSPC, and saw 2 or more patients with mCSPC per month.

Eligibility criteria for patients at the time of data collection included being diagnosed with mCSPC between July 2018 and January 2022, having either a current mCSPC diagnosis (at the time of data collection) or an earlier mCSPC diagnosis that progressed to metastatic castration-resistant prostate cancer, receiving systemic drug treatment for mCSPC for a minimum of 3 months, not being involved in a clinical trial when diagnosed with mCSPC, being between ages 18 and 89 years at mCSPC diagnosis, and not being deceased (eFigure in Supplement 1).

Statistical Analysis

The main study outcome was the likelihood of receiving TI compared with not receiving TI using odds ratio (OR). Bivariate analyses were conducted for 2 patient groups (patients who received TI compared with those who did not receive TI). For continuous variables, t tests were used; the Mann-Whitney test was used for ordinal variables, the Fisher exact test was used for categorical variables, and χ² tests were used if the Fisher exact test could not be calculated. The cutoff for significance was a 2-sided P < .05.

Physician-reported prostate-specific antigen (PSA) reduction goals (ie, PSA reduction desired by the physician) were applied to each of the corresponding physician’s patients, and a Wald test using a bivariate logistic regression model was used to assess the association between PSA reduction goals and TI. Multivariable analyses were conducted to assess factors associated with receiving first-line TI including elastic-net regression⁴⁰ and mixed-effects logistic regression models. Covariates considered for entry included baseline patient characteristics, physician characteristics, and predetermined groups for reasons for choice, determined by expert opinion: efficacy, safety and tolerability, sequencing, financial expense, patient opinion, and guidelines. For likelihood of TI, ORs were reported. Principal components analyses and sensitivity analyses were conducted, including multicollinearity assessments, inclusion and exclusion of interaction terms within the elastic-net regression, and a comparison of mixed-effects and fixed-effects logistic regression models (eMethods in Supplement 1). Descriptive statistics were derived using the software packages UNICOM Intelligence Reporter (UNICOM Systems Inc) and SPSS Data Collection Survey Reporter, version 7.5 (IBM Inc). All other statistical analyses were performed in Stata, version 17.0 (StataCorp LLC).

Results

Demographics and Clinical Characteristics

Overall, 131 US-based physicians were invited to participate in the survey and 107 provided data on 621 male patients with a current or previous diagnosis of mCSPC; 617 patients met analysis criteria of first-line TI or no TI (mean [SD] age, 68.6 [8.1] years). A median of 8 (IQR, 1-8) patient record forms were completed per physician. Of participating physicians, 65 (60.7%) were medical oncologists and 42 (39.3%) were urologists; 68 (63.6%) treated patients in a community hospital and 39 (36.4%) in an academic or cancer center (eTable 1 in Supplement 1). The median number of patients with prostate cancer seen monthly was 196 (IQR, 224-476).

Among the total patients, 153 (24.8%) were African American, 50 (8.1%) were Hispanic or Latino, 358 (58.0%) were White or Caucasian, and 56 (9.1%) were of other race or ethnicity (Table 1). More than half of the patients (349 [56.6%]) were beneficiaries of Medicare, 176 (28.5%) of private insurance, and 50 (8.1%) of Medicaid (or equivalent) (Table 1). Metastatic disease burden was classified by the physician, per their own definition, as a high-volume disease in 186 patients (30.1%), and 134 patients (21.7%) had lung or liver metastases (Table 1). Baseline disease characteristics were generally worse for patients who received first-line TI compared with those who did not, with significant differences in Gleason grade group (groups range from 1 [Gleason score of ≤6; low-grade cancer] to 5 [Gleason score of 9 or 10; high-grade cancer]), high-volume disease, PSA levels, and metastases sites (Table 1).

Table 1. Demographic and Clinical Characteristics of Patients With mCSPC Treated by US-Based Physicians by First-Line TI^a.

Characteristic	Patient group			P value
Characteristic	First-line TI (n = 187)	No first-line TI (n = 430)	Total (N = 617)	P value
Age at the start of first-line mCSPC treatment, y
Mean (SD)	68.4 (7.9)	68.7 (8.2)	68.6 (8.1)	.72
Median (IQR)	68 (63-74)	69 (63-74)	68 (63-74)	.72
Race or ethnicity
African American	46 (24.6)	107 (24.9)	153 (24.8)	.16
Hispanic or Latino	18 (9.6)	32 (7.4)	50 (8.1)
White or Caucasian	113 (60.4)	245 (57.0)	358 (58.0)
Other^b	10 (5.3)	46 (10.7)	56 (9.1)
Health insurance at the start of first-line mCSPC treatment
Medicaid or state equivalent	13 (7.0)	37 (8.6)	50 (8.1)	.49
Medicare, Medicare Part D, Medicare Medical Savings Account, or Medicare Advantage	109 (58.3)	240 (55.8)	349 (56.6)
Private	53 (28.3)	123 (28.6)	176 (28.5)
Other	2 (1.1)	11 (2.6)	13 (2.1)
No insurance coverage	4 (2.1)	4 (0.9)	8 (1.3)
Do not know	6 (3.2)	15 (3.5)	21 (3.4)
ECOG performance status score prior to first-line mCSPC treatment being chosen
0-1	157 (84.0)	357 (83.0)	514 (83.3)	.99
≥2	30 (16.0)	68 (15.8)	98 (15.9)
Unknown or not assessed	0	5 (1.2)	5 (0.8)
Gleason grade group prior to first-line mCSPC treatment being chosen^c
1 and 2	12 (6.4)	64 (14.9)	76 (12.3)	<.001
3	22 (11.8)	67 (15.6)	89 (14.4)
4	56 (29.9)	134 (31.2)	190 (30.8)
5	54 (28.9)	85 (19.8)	139 (22.5)
Unknown or not assessed	43 (23.0)	80 (18.6)	123 (19.9)
High-volume disease prior to first-line mCSPC treatment being chosen^d
Yes	73 (39.0)	113 (26.3)	186 (30.1)	.01
No	107 (57.2)	266 (61.9)	373 (60.5)
Do not know	7 (3.7)	51 (11.9)	58 (9.4)
Patients with PSA results prior to first-line mCSPC treatment being chosen (log transformed)
No.	168	360	528	.03
Mean (SD)	3.3 (1.2)	3.0 (1.2)	3.1 (1.2)
Median (IQR)	2.9 (2.6-3.8)	2.9 (2.3-3.6)	2.9 (2.4-3.7)
Metastases sites prior to first-line mCSPC treatment being chosen
Nonvisceral^e	111 (59.4)	316 (73.5)	427 (69.2)	<.001
Bone only	93 (49.7)	230 (53.5)	323 (52.4)
Nonregional or distant lymph nodes only	18 (9.6)	86 (20.0)	104 (16.9)
Lung or liver	44 (23.5)	90 (20.9)	134 (21.7)
Other	32 (17.1)	24 (5.6)	56 (9.1)
CCI at the start of first-line mCSPC treatment
Mean (SD)	6.6 (1.0)	6.7 (1.2)	6.6 (1.2)	.53
Median (IQR)	6.0 (6-7)	6.0 (6-7)	6.0 (6-7)	.53
Timing of metastatic disease
De novo	164 (87.7)	352 (81.9)	516 (83.6)	.08
Recurrent	23 (12.3)	78 (18.1)	101 (16.4)	.08

Open in a new tab

Abbreviations: CCI, Charlson Comorbidity Index; ECOG, Eastern Cooperative Oncology Group; mCSPC, metastatic castration-sensitive prostate cancer; PSA, prostate-specific antigen; TI, treatment intensification.

^{^a}

Data are presented as No. (%) unless otherwise indicated. TI included an androgen receptor pathway inhibitor (enzalutamide, apalutamide, abiraterone, or darolutamide), chemotherapy, or both added to androgen deprivation therapy.

^{^b}

Other included Asian (Indian subcontinent), Asian (other), Middle Eastern, mixed race, Native American, or Southeast Asian.

^{^c}

Group 1 indicates Gleason scores of 6 or less (low-grade cancer); group 2, a score of 7 (3 + 4 or any other score combination that sums to 7 except 4 + 3; medium-grade cancer); group 3, a score of 7 (4 + 3; medium-grade cancer); group 4, a score of 8 (high-grade cancer); group 5, scores of 9 or 10 (high-grade cancer).

^{^d}

High-volume disease was defined per the physician’s own definition.

^{^e}

The cumulative total of bone only and nonregional or distant lymph nodes only.

mCSPC Treatment Patterns

Overall, 187 patients (30.3%) received first-line TI for mCSPC. Among these, 160 (25.9%) received ADT and an ARPI; 19 (3.1%) received ADT and chemotherapy; and 8 (1.3%) received ADT, an ARPI, and chemotherapy (Table 2). The remaining 430 (69.7%) did not receive first-line TI. Ninety-eight patients with mCSPC (15.9%) later received treatment for metastatic castration-resistant prostate cancer (eTable 2 in Supplement 1).

Table 2. Treatment Received for mCSPC.

Treatment	Patients’ physician specialty, No. (%)
Treatment	Treated by a medical oncologist (n = 344)	Treated by a urologist (n = 273)	All patients (N = 617)
First-line mCSPC treatment prescribed after mCSPC diagnosis
TI^a	93 (27.0)	94 (34.4)	187 (30.3)
ADT and an ARPI	79 (23.0)	81 (29.7)	160 (25.9)
ADT and chemotherapy	11 (3.2)	8 (2.9)	19 (3.1)
ADT, an ARPI, and chemotherapy	3 (0.9)	5 (1.8)	8 (1.3)
No TI	251 (73.0)	179 (65.6)	430 (69.7)
ADT alone	204 (59.3)	117 (42.9)	321 (52.0)
ADT and a first-generation NSAA	47 (13.7)	62 (22.7)	109 (17.7)
Treatment prescribed while patient was considered to have mCSPC (first and subsequent)
TI^a	188 (54.7)	165 (60.4)	353 (57.2)
ADT and an ARPI	167 (48.5)	145 (53.1)	312 (50.6)
ADT and chemotherapy	18 (5.2)	15 (5.5)	33 (5.3)
ADT, an ARPI, and chemotherapy	3 (0.9)	5 (1.8)	8 (1.3)
No TI	156 (45.3)	108 (39.6)	264 (42.8)
ADT alone	135 (39.2)	78 (28.6)	213 (34.5)
ADT and a first-generation NSAA	21 (6.1)	30 (11.0)	51 (8.3)

Open in a new tab

Abbreviations: ADT, androgen deprivation therapy; ARPI, androgen receptor pathway inhibitor; mCSPC, metastatic castration-sensitive prostate cancer; NSAA, nonsteroidal antiandrogen; TI, treatment intensification.

^{^a}

Included an ARPI (enzalutamide, apalutamide, abiraterone, or darolutamide), chemotherapy, or both added to ADT.

When first-line and subsequent-line (defined as treatment prescribed to intensify or change the initial drug treatment when the patient was considered to have mCSPC) treatments were combined, 353 patients (57.2%) received TI. Thus, among the 617 total patients, 166 (26.9%) received delayed TI (Table 2). Reasons for delayed TI will be explored in a subsequent study; these patients were grouped as no TI for this analysis.

Bivariate Analysis of Physician-Reported Reasons for First-Line mCSPC Treatment Choice

The most frequently cited physician-reported reasons for first-line mCSPC treatment choice for both TI and no TI groups were tolerability, guideline recommendations, familiarity with treatment, and better QOL (Figure 1A and eTable 3 in Supplement 1). The top reason for treatment choice was “Treatment has a tolerable side-effects profile/fewer adverse events” (TI: 121 [64.7%]; no TI: 252 [58.6%]; P = .18), followed by “This is what is recommended in the treatment guidelines” (TI: 115 [61.5%]; no TI: 230 [53.5%]; P = .08). A similar proportion of physicians cited “QOL is important to me, and this treatment offers better overall QOL” as the reason for first-line treatment choice in both the TI (74 [39.6%]) and the no TI (157 [36.5%]) groups. High PSA level was more frequently cited in the TI (73 [39.0%]) compared with the no TI (79 [18.4%]) (P < .001) group. Ease of treatment administration was more frequently cited in the no TI group (113 [26.3%]) compared with the TI (33 [17.6%]) (P = .02) group.

Figure 1. — (A) Treatment intensification (TI) involved the addition of an androgen receptor pathway inhibitor (ARPI [enzalutamide, apalutamide, abiraterone, or darolutamide]), chemotherapy, or both to androgen deprivation therapy. Percentages have been calculated out of the respective TI status base. Physicians could give multiple responses. There were 617 total patients, of whom 187 (30.3%) received TI and 430 (69.7%) did not. Data are shown in eTable 3 in Supplement 1. (B) There were 207 patients treated by oncologists or urologists; 114 were treated by oncologists and 93 were treated by urologists. mCSPC indicates metastatic castration-sensitive prostate cancer; PSA, prostate-specific antigen; QOL, quality of life.

Reasons grouped as patient clinical characteristics were associated with physicians’ treatment decisions in 522 patients (84.6%) (eTable 3 in Supplement 1); of these, high PSA levels (TI: 73 [39.0%]; no TI: 79 [18.4%]; P = .001), Gleason score (TI: 43 [23.0%]; no TI: 81 [18.8%]; P = .27), de novo disease (TI: 32 [17.1%]; no TI: 62 [14.4%]; P = .40), and high-volume disease (TI: 35 [18.7%]; no TI: 39 [9.1%]; P = .001) were most frequently cited. Reasons driven by global belief about better treatment efficacy were associated with physicians’ treatment decisions in a higher proportion of patients who received TI (68 [36.4%]) compared with those who did not receive TI (125 [29.1%]) (P = .07); physicians cited “This treatment is superior in efficacy with regards to prolonging the castration-sensitive phase” as a reason for treatment choice for 55 patients (29.4%) who received TI and for 82 (19.1%) who did not receive TI (P = .006).

Reasons related to reimbursement or treatment access were associated with physician decisions in a similar proportion of patients who received TI and those who did not receive TI (81 [43.3%] vs 219 [50.9%]; P = .10). Only 21 patients (4.9%) were not prescribed TI based on the physician-reported reason that their preferred treatment for this patient was not covered by health insurance. For patients whose physicians did not prescribe an ARPI or any subsequent lines of treatment (n = 207), perceptions about ARPI tolerability (79 [38.2%]) and perceived lack of clinical trial evidence of survival improvements with ARPIs (65 [31.4%]) were most cited as reasons for not prescribing an ARPI (Figure 1B).

Physician-Reported PSA Reduction Goals

Overall, 91 physicians (85.0%) reported that they worked toward a PSA reduction goal as a percentage decrease, whereas 55 (51.4%) worked toward a goal in nanograms per milliliters (to convert to micrograms per liter, multiply by 1.0) (Table 3); 39 (36.4%) used both measures. The median PSA reduction goals were 50% (IQR, 33%-80%) or 2.0 ng/mL (IQR, 1.0-5.0 ng/mL).

Table 3. Physician-Reported PSA Reduction Goals in mCSPC and Likelihood of Receiving TI^a.

Variable	Physician specialty			P value
Variable	Medical oncologist	Urologist	Total	P value
PSA reduction goal
Reported as % PSA decline
No.	55	36	91
Median (IQR)	50.0 (25.0-75.0)	75.0 (50.0-90.0)	50.0 (33.0-80.0)	NA
0-49	23 (41.8)	3 (8.3)	26 (28.6)
50-74	17 (30.9)	14 (38.9)	31 (34.1)
75-100	15 (27.3)	19 (52.8)	34 (37.4)
Reported as ng/mL
No.	28	27	55
Median (IQR)	3.5 (1.0-6.6)	1.0 (1.0-4.0)	2.0 (1.0-5.0)	NA
>10	4 (14.3)	3 (11.1)	7 (12.7)
5-10	7 (25.0)	3 (11.1)	10 (18.2)
1-<5	9 (32.1)	5 (18.5)	14 (25.5)
<1	8 (28.6)	17 (63.0)	25 (45.5)
Likelihood of receiving TI
PSA reduction goal, OR (95% CI), %^b
75-100	NA	NA	1.63 (1.04-2.56)	.03
50-74	NA	NA	0.90 (0.55-1.46)	.67
0-49 (base case)	NA	NA	1 [Reference]	NA

Open in a new tab

Abbreviations: mCSPC, metastatic castration-sensitive prostate cancer; NA, not applicable; OR, odds ratio; PSA, prostate-specific antigen; TI, treatment intensification.

SI conversion: To convert PSA reduction goal from nanograms per milliliter to micrograms per liter, multiply by 1.0.

^{^a}

^{^b}

Due to low patient numbers, ORs were only computed for all physicians and for PSA reduction goals in percentage.

The bivariate analysis showed that physicians who aimed for larger PSA reduction (75%-100%) were more likely to prescribe first-line TI compared with physicians who had smaller PSA reduction goals (0%-49%) (OR, 1.63 [95% CI, 1.04-2.56]; P = .03) (Table 3). Compared with medical oncologists, urologists had larger PSA reduction goals (Table 3) and higher rates of prescribing TI for patients with mCSPC (Table 2).

Multivariable Analysis

Multivariable regression analysis of 332 patients and 65 physicians with sufficient data showed that patients whose physician chose treatment based on guideline recommendations were more likely to receive TI than patients whose physician did not report these reasons (OR, 3.46 [95% CI, 1.32-9.08]; P = .01) (Figure 2). Other physician-related factors, including specialty, practice setting, concerns about drug safety and tolerability, patient QOL, and insurance reimbursement or access, were not associated with first-line TI . Cancer characteristics associated with an increased likelihood of receiving first-line TI were visceral or other metastases and Gleason grade group 5 (Figure 2). In contrast to the bivariate analysis, PSA reduction goals were not associated with first-line TI . Similar outcomes were found if patients who received chemotherapy as first-line treatment for mCSPC were excluded. Outcomes from the principal components analyses (eTable 4 in Supplement 1) and the sensitivity analysis were consistent with the multivariable regression analyses.

Figure 2. — The figure only shows physician-reported reasons associated with likelihood of TI. TI involved the addition of an androgen receptor pathway inhibitor (ARPI [enzalutamide, apalutamide, abiraterone, or darolutamide]) and/or chemotherapy to androgen deprivation therapy. Other physician-related factors, including physician specialty, practice setting, concerns about drug safety and tolerability, patient quality of life, and insurance reimbursement or access, did not show associations with first-line TI. OR indicates odds ratio.

Discussion

Phase 3 clinical trials have shown improved survival with TI in mCSPC^{1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17} and guidelines recommend TI as standard of care.^18,19,20,21 However, several US studies suggest that many patients are not receiving TI in clinical practice.^{22,23,24,25,26,27,28,29,30,31,32,33,34,35} This study highlights several reasons for underutilization of TI using treatment data extracted from patient medical records and physician self-reported reasons for treatment choice.

Similar to claims-based studies of patients from the US,^{22,23,24,25,26,27,28,29,30,31,32,33} we found that most patients (69.7%) did not receive TI as first-line treatment for mCSPC. Unsurprisingly, baseline tumor characteristics were generally worse in patients who received TI compared with those who did not. Accordingly, physician-reported reasons for first-line treatment choice based on high PSA levels, high-risk disease, or high-volume disease were significantly greater in patients who received TI compared with those who did not. The multivariable analysis also showed that Gleason grade and metastasis site were associated with an increased likelihood of receiving TI. The finding that patients with high-risk disease were more likely to receive TI is consistent with previously reported data.³⁵ However, data from clinical trials^{1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17} and updated guidelines^18,19,20,21 show that TI is beneficial across all patients with mCSPC who are able to tolerate more aggressive treatment and should not be restricted to those with the worst prognosis.

Overall, efficacy reasons were associated with greater probability of first-line treatment choice for TI compared with no TI, although individual efficacy reasons were generally reported in fewer than 20% of all patients. In 19.1% of patients who were not prescribed TI, physicians believed that not prescribing TI was superior in efficacy, which suggests divergent interpretation of clinical trial data or misunderstanding of the evidence. Furthermore, for 31.4% of patients, the physician-cited reason for not prescribing an ARPI was perceived lack of clinical trial evidence of survival improvements with ARPIs. Tolerability, QOL, and experience were also associated with prescribing and not prescribing TI, which further highlights differing perspectives and interpretation of TI data. For example, although a favorable tolerability profile and fewer adverse events were a physician-reported reason for prescribing TI in 64.7% of patients, they were also a physician-reported reason in 58.6% of patients who were not prescribed TI. Additionally, the top physician-reported reason for not prescribing an ARPI was that ARPIs would need to have a better tolerability profile than their chosen regimen (38.2% of patients). Similarly, for QOL, 39.6% of patients who received TI had a physician-reported reason that this treatment provided better overall QOL, but 36.5% of patients who were not prescribed TI had the same physician-reported reason for their treatment. This latter finding is similar to a 2020 global analysis, in which QOL was associated with no TI in 32.1% of patients.³⁵ These findings were observed despite data from clinical trials showing that TI is well-tolerated^{1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17} and maintains QOL^7,12,41,42 while improving survival outcomes. Results from this study highlight differences in interpretation and a need to increase awareness of TI clinical trial data.^{1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17} A recent physician interview study also identified lack of knowledge, including trial data, as a barrier to TI.⁴³

PSA is an important prognostic biomarker in patients with mCSPC who receive ADT with or without TI.^{44,45,46,47,48} Although the bivariate analysis in our study showed that physicians aiming for larger PSA reduction goals compared with smaller PSA reduction goals were more likely to provide TI, when additional covariates were included in the multivariable analysis, PSA reduction goals were no longer significant. This suggests that PSA reduction goals are important decision drivers, but the idea of improved efficacy (ie, lower PSA) was better captured by other variables in our multivariable model.

The PSA reduction goals that physicians work toward are particularly notable, as PSA reduction is not an end point in the labels or registration trials of these regimens. Nonetheless, 85.0% of physicians reported focusing on a percentage decrease goal with a median of 50% reduction as adequate; 51.4% reported a goal in nanograms per milliliters with a median of 2.0 ng/mL as adequate. These goals are unjustified, as they are far from achieving a maximal PSA reduction to undetectable levels (ie, <0.2 ng/mL), which has retrospectively demonstrated clinical benefits compared with less-stringent PSA goals.⁴⁹ Educating physicians about PSA reduction goals may increase the number of patients receiving first-line TI in mCSPC and may improve patient outcomes.

We hypothesized that reimbursement and treatment access would be important drivers for treatment decisions. However, only 4.9% of patients were not prescribed TI based on the physician-reported reason that their preferred treatment was not covered by the patient’s health insurance, which suggests that access is not a barrier. Treatment choices were rarely driven by patient opinion and behavior.

Our multivariable analysis used variables selected by an elastic-net model to have a role in treatment decisions; however, “driven by guidelines” was the only physician-reported reason associated with the likelihood of prescribing first-line TI in mCSPC. Despite this difference, the bivariate analysis showed that physicians cited “This is what is recommended in the guidelines” as a reason for treatment choice in over half of patients who were not prescribed TI (53.5%), which highlights a lack of understanding of guidelines and a need for education.

Limitations

This study has several limitations. The ARW survey was not a true random sample of physicians’ most recent eligible patients and may include a higher proportion of patients who consulted with their physician more frequently. Additionally, although minimal inclusion criteria were used to help to ensure a broad sample of physicians, inclusion was influenced by willingness to participate. Nonresponse bias was possible, as physicians represented a pragmatic sample of the consulting population. Patient number varied by physician; random intercepts were included within the mixed-effects regression to limit the effect of this.

Patient diagnosis was based primarily on the judgment of responding physicians; a formalized diagnostic checklist was not mandated. The data were largely dependent on accurate reporting by physicians, which may have been subject to recall bias. Missing data occurred if physicians had imperfect knowledge on questions asked. Any patients with missing values for a variable were removed from all analyses in which that variable was used but were still eligible for inclusion in other analyses. Patient-level socioeconomic status was not collected and patient-level timing of metastatic disease was not considered for entry in the multivariable analysis. Life expectancy was also not collected (not routinely calculated) but is reflected in age, the Charlson Comorbidity Index, and disease volume. Finally, our findings do not account for the triplet therapy of ADT, an ARPI, and chemotherapy, which was not approved during the study period.

Conclusions

This survey study, which analyzed data from a US clinical practice survey, showed low rates of patients receiving TI for first-line mCSPC therapy despite guideline recommendations. The most frequent physician-reported reasons for treatment choice were similar for TI and no TI, which suggested a divergent interpretation of guideline recommendations and efficacy and safety data from clinical trials. Improving physicians’ knowledge of guideline-based therapies, increasing understanding of TI clinical trial data, and using appropriate PSA target goals may help overcome the low rates of first-line TI in mCSPC and thereby may improve patient outcomes.

Supplement 1.

eMethods

eTable 1. Characteristics of US-Based Physician Participants

eTable 2. Treatments Received for mCRPC

eTable 3. Physician-Reported Reasons for First-Line mCSPC Treatment Choice Grouped by Expert Opinion

eTable 4. Principal Components Analyses. TI With an ARPI and/or Chemotherapy: Mixed-Effects Logistic Regression Model Using Variables Selected From the Elastic-Net Model

eFigure. Data Collection Methodology

eReference

jamanetwopen-e2448707-s001.pdf^{(418.3KB, pdf)}

Supplement 2.

Data Sharing Statement

jamanetwopen-e2448707-s002.pdf^{(15.3KB, pdf)}

References

1.Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737-746. doi: 10.1056/NEJMoa1503747 [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Kyriakopoulos CE, Chen YH, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018;36(11):1080-1087. doi: 10.1200/JCO.2017.75.3657 [DOI] [PMC free article] [PubMed] [Google Scholar]
3.James ND, Sydes MR, Clarke NW, et al. ; STAMPEDE Investigators . Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163-1177. doi: 10.1016/S0140-6736(15)01037-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Clarke NW, Ali A, Ingleby FC, et al. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019;30(12):1992-2003. doi: 10.1093/annonc/mdz396 [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Fizazi K, Tran N, Fein L, et al. ; LATITUDE Investigators . Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352-360. doi: 10.1056/NEJMoa1704174 [DOI] [PubMed] [Google Scholar]
6.Fizazi K, Tran N, Fein L, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019;20(5):686-700. doi: 10.1016/S1470-2045(19)30082-8 [DOI] [PubMed] [Google Scholar]
7.Chi KN, Protheroe A, Rodríguez-Antolín A, et al. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018;19(2):194-206. doi: 10.1016/S1470-2045(17)30911-7 [DOI] [PubMed] [Google Scholar]
8.James ND, de Bono JS, Spears MR, et al. ; STAMPEDE Investigators . Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377(4):338-351. doi: 10.1056/NEJMoa1702900 [DOI] [PMC free article] [PubMed] [Google Scholar]
9.James ND, Clarke NW, Cook A, et al. ; STAMPEDE Trials Collaborative Group . Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer. 2022;151(3):422-434. doi: 10.1002/ijc.34018 [DOI] [PMC free article] [PubMed] [Google Scholar]
10.Chi KN, Agarwal N, Bjartell A, et al. ; TITAN Investigators . Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381(1):13-24. doi: 10.1056/NEJMoa1903307 [DOI] [PubMed] [Google Scholar]
11.Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39(20):2294-2303. doi: 10.1200/JCO.20.03488 [DOI] [PubMed] [Google Scholar]
12.Agarwal N, McQuarrie K, Bjartell A, et al. ; TITAN Investigators . Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2019;20(11):1518-1530. doi: 10.1016/S1470-2045(19)30620-5 [DOI] [PubMed] [Google Scholar]
13.Davis ID, Martin AJ, Stockler MR, et al. ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group . Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381(2):121-131. doi: 10.1056/NEJMoa1903835 [DOI] [PubMed] [Google Scholar]
14.Armstrong AJ, Azad AA, Iguchi T, et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2022;40(15):1616-1622. doi: 10.1200/JCO.22.00193 [DOI] [PMC free article] [PubMed] [Google Scholar]
15.Smith MR, Hussain M, Saad F, et al. ; ARASENS Trial Investigators . Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386(12):1132-1142. doi: 10.1056/NEJMoa2119115 [DOI] [PMC free article] [PubMed] [Google Scholar]
16.Fizazi K, Foulon S, Carles J, et al. ; PEACE-1 Investigators . Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022;399(10336):1695-1707. doi: 10.1016/S0140-6736(22)00367-1 [DOI] [PubMed] [Google Scholar]
17.Sweeney CJ, Martin AJ, Stockler MR, et al. ; ENZAMET Trial Investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group . Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(4):323-334. doi: 10.1016/S1470-2045(23)00063-3 [DOI] [PubMed] [Google Scholar]
18.Cornford P, Tilki D, van den Bergh RCN, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. European Association of Urology . April 2024. Accessed April 10, 2024. https://d56bochluxqnz.cloudfront.net/documents/full-guideline/EAU-EANM-ESTRO-ESUR-ISUP-SIOG-Guidelines-on-Prostate-Cancer-2024_2024-04-09-132035_ypmy.pdf
19.Fizazi K, Gillessen S; ESMO Guidelines Committee . Updated treatment recommendations for prostate cancer from the ESMO Clinical Practice Guideline considering treatment intensification and use of novel systemic agents. Ann Oncol. 2023;34(6):557-563. doi: 10.1016/j.annonc.2023.02.015 [DOI] [PubMed] [Google Scholar]
20.Lowrance W, Dreicer R, Jarrard DF, et al. Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023). J Urol. 2023;209(6):1082-1090. doi: 10.1097/JU.0000000000003452 [DOI] [PubMed] [Google Scholar]
21.Virgo KS, Rumble RB, Talcott J. Initial management of noncastrate advanced, recurrent, or metastatic prostate cancer: ASCO Guideline update. J Clin Oncol. 2023;41(20):3652-3656. doi: 10.1200/JCO.23.00155 [DOI] [PubMed] [Google Scholar]
22.Freedland SJ, Agarwal N, Ramaswamy K, et al. Real-world utilization of advanced therapies and racial disparity among patients with metastatic castration-sensitive prostate cancer (mCSPC): a Medicare database analysis. Abstract presented at: 2021 American Society of Clinical Oncology Annual Meeting I; May 28, 2021. Abstract 5073.
23.Freedland SJ, Sandin R, Sah J, et al. Treatment patterns and survival in metastatic castration-sensitive prostate cancer in the US Veterans Health Administration. Cancer Med. 2021;10(23):8570-8580. doi: 10.1002/cam4.4372 [DOI] [PMC free article] [PubMed] [Google Scholar]
24.Freedland SJ, Sandin R, Tagawa ST, et al. 609P Treatment patterns and overall survival (OS) in metastatic castration-sensitive prostate cancer (mCSPC) from 2006 to 2019. Ann Oncol. 2021;32(suppl 5):S650-S651. doi: 10.1016/j.annonc.2021.08.1122 [DOI] [Google Scholar]
25.George DJ, Agarwal N, Ramaswamy K, et al. 616P Real-world utilization of advanced therapies by metastatic site and age among patients with metastatic castration-sensitive prostate cancer (mCSPC): a Medicare database analysis. Ann Oncol. 2021;32(suppl 5):S655-S656. doi: 10.1016/j.annonc.2021.08.1129 [DOI] [Google Scholar]
26.George DJ, Agarwal N, Rider JR, et al. Real-world treatment patterns among patients diagnosed with metastatic castration-sensitive prostate cancer (mCSPC) in community oncology settings. Abstract presented at: 2021 American Society of Clinical Oncology Annual Meeting I; May 28, 2021. Abstract 5074.
27.Ryan CJ, Ke X, Lafeuille MH, et al. Management of patients with metastatic castration-sensitive prostate cancer in the real-world setting in the United States. J Urol. 2021;206(6):1420-1429. doi: 10.1097/JU.0000000000002121 [DOI] [PMC free article] [PubMed] [Google Scholar]
28.Swami U, Hong A, El-Chaar NN, et al. Real-world first-line (1L) treatment patterns in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a U.S. health insurance database. Abstract presented at: 2021 American Society of Clinical Oncology Annual Meeting I; May 28, 2021; virtual. Abstract 5072.
29.Swami U, Sinnott JA, Haaland B, et al. Treatment pattern and outcomes with systemic therapy in men with metastatic prostate cancer in the real-world patients in the United States. Cancers (Basel). 2021;13(19):4951. doi: 10.3390/cancers13194951 [DOI] [PMC free article] [PubMed] [Google Scholar]
30.Swami U, Hong A, El-Chaar NN, et al. Underutilization of standard of care (SOC) treatment intensification in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) by specialty. Abstract presented at: 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 16, 2022; San Francisco, CA. Abstract 183.
31.Swami U, Hong A, El-Chaar NN, et al. The role of physician specialty in the underutilization of standard-of-care treatment intensification in patients with metastatic castration-sensitive prostate cancer. J Urol. 2023;209(6):1120-1131. doi: 10.1097/JU.0000000000003370 [DOI] [PubMed] [Google Scholar]
32.Tagawa ST, Sandin R, Sah J, Mu Q, Freedland SJ. 679P Treatment patterns of metastatic castration-sensitive prostate cancer (mCSPC): a real-world evidence study. Ann Oncol. 2020;31(suppl 4):S541-S542. doi: 10.1016/j.annonc.2020.08.938 [DOI] [Google Scholar]
33.Heath EI, Dyson GE, Cackowski FC, Hafron J, Powell I. Treatment intensification patterns and utilization in patients with metastatic castration-sensitive prostate cancer. Clin Genitourin Cancer. 2022;20(6):524-532. doi: 10.1016/j.clgc.2022.06.017 [DOI] [PubMed] [Google Scholar]
34.Barata PC, Leith A, Ribbands A, et al. Real-world treatment patterns among patients with metastatic castration-resistant prostate cancer: results from an international study. Oncologist. 2023;28(9):e737-e747. doi: 10.1093/oncolo/oyad046 [DOI] [PMC free article] [PubMed] [Google Scholar]
35.Leith A, Ribbands A, Kim J, et al. Impact of next-generation hormonal agents on treatment patterns among patients with metastatic hormone-sensitive prostate cancer: a real-world study from the United States, five European countries and Japan. BMC Urol. 2022;22(1):33. doi: 10.1186/s12894-022-00979-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
36.Gonzalez JM, Ganguli A, Morgans AK, et al. Discrete-choice experiment to understand the preferences of patients with hormone-sensitive prostate cancer in the USA, Canada, and the UK. Patient. 2023;16(6):607-623. doi: 10.1007/s40271-023-00638-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
37.Code of Conduct and Adverse Event Reporting Guidelines. European Pharmaceutical Market Research Association (EPHMRA) . Updated 2021. Accessed August 18, 2022. https://www.ephmra.org/code-conduct-aer
38.Office for Civil Rights Privacy Brief. Summary of the HIPAA Privacy Rule. US Department of Health and Human Services . Updated May 2003. Accessed August 18, 2022. http://www.hhs.gov/sites/default/files/privacysummary.pdf
39.Health Information Privacy. HITECH Act Enforcement Interim Final Rule. US Department of Health and Human Services . June 16, 2017. Accessed August 18, 2022. https://www.hhs.gov/hipaa/for-professionals/special-topics/hitech-act-enforcement-interim-final-rule/index.html
40.Zou H, Hastie T. Regularization and variable selection via the elastic net. J R Stat Soc Series B Stat Methodol. 2005;67(2):301-320. doi: 10.1111/j.1467-9868.2005.00503.x [DOI] [Google Scholar]
41.Stockler MR, Martin AJ, Davis ID, et al. ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) . Health-related quality of life in metastatic, hormone-sensitive prostate cancer: ENZAMET (ANZUP 1304), an international, randomized phase III trial led by ANZUP. J Clin Oncol. 2022;40(8):837-846. doi: 10.1200/JCO.21.00941 [DOI] [PMC free article] [PubMed] [Google Scholar]
42.Stenzl A, Dunshee C, De Giorgi U, et al. Effect of enzalutamide plus androgen deprivation therapy on health-related quality of life in patients with metastatic hormone-sensitive prostate cancer: an analysis of the ARCHES randomised, placebo-controlled, phase 3 study. Eur Urol. 2020;78(4):603-614. doi: 10.1016/j.eururo.2020.03.019 [DOI] [PubMed] [Google Scholar]
43.Loeb S, Agarwal N, El-Chaar NN, et al. Barriers and facilitators to first-line (1L) treatment intensification (TI) in metastatic castration-sensitive prostate cancer (mCSPC): the IMPLEMENT study. Abstract presented at: 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium; January 29, 2024; San Francisco, CA. Abstract 224.
44.Choueiri TK, Xie W, D’Amico AV, et al. Time to prostate-specific antigen nadir independently predicts overall survival in patients who have metastatic hormone-sensitive prostate cancer treated with androgen-deprivation therapy. Cancer. 2009;115(5):981-987. doi: 10.1002/cncr.24064 [DOI] [PMC free article] [PubMed] [Google Scholar]
45.Matsubara N, Chi KN, Özgüroğlu M, et al. Correlation of prostate-specific antigen kinetics with overall survival and radiological progression-free survival in metastatic castration-sensitive prostate cancer treated with abiraterone acetate plus prednisone or placebos added to androgen deprivation therapy: post hoc analysis of phase 3 LATITUDE study. Eur Urol. 2020;77(4):494-500. doi: 10.1016/j.eururo.2019.11.021 [DOI] [PubMed] [Google Scholar]
46.Briones J, Khan M, Sidhu AK, Zhang L, Smoragiewicz M, Emmenegger U. Population-based study of docetaxel or abiraterone effectiveness and predictive markers of progression free survival in metastatic castration-sensitive prostate cancer. Front Oncol. 2021;11:658331. doi: 10.3389/fonc.2021.658331 [DOI] [PMC free article] [PubMed] [Google Scholar]
47.Fujimoto N, Shiota M, Matsukawa T, et al. Three-month prostate-specific antigen level after androgen deprivation therapy predicts survival in patients with metastatic castration-sensitive prostate cancer. In Vivo. 2021;35(2):1101-1108. doi: 10.21873/invivo.12355 [DOI] [PMC free article] [PubMed] [Google Scholar]
48.Iacovelli R, Ciccarese C, Caffo O, et al. The role of fast and deep PSA response in castration-sensitive prostate cancer. Anticancer Res. 2022;42(1):165-172. doi: 10.21873/anticanres.15470 [DOI] [PubMed] [Google Scholar]
49.Hussain M, Tangen CM, Higano C, et al. ; Southwest Oncology Group Trial 9346 (INT-0162) . Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol. 2006;24(24):3984-3990. doi: 10.1200/JCO.2006.06.4246 [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement 1.

eMethods

eTable 1. Characteristics of US-Based Physician Participants

eTable 2. Treatments Received for mCRPC

eTable 3. Physician-Reported Reasons for First-Line mCSPC Treatment Choice Grouped by Expert Opinion

eTable 4. Principal Components Analyses. TI With an ARPI and/or Chemotherapy: Mixed-Effects Logistic Regression Model Using Variables Selected From the Elastic-Net Model

eFigure. Data Collection Methodology

eReference

jamanetwopen-e2448707-s001.pdf^{(418.3KB, pdf)}

Supplement 2.

Data Sharing Statement

jamanetwopen-e2448707-s002.pdf^{(15.3KB, pdf)}

[zoi241364r1] 1.Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737-746. doi: 10.1056/NEJMoa1503747 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r2] 2.Kyriakopoulos CE, Chen YH, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018;36(11):1080-1087. doi: 10.1200/JCO.2017.75.3657 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r3] 3.James ND, Sydes MR, Clarke NW, et al. ; STAMPEDE Investigators . Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163-1177. doi: 10.1016/S0140-6736(15)01037-5 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r4] 4.Clarke NW, Ali A, Ingleby FC, et al. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019;30(12):1992-2003. doi: 10.1093/annonc/mdz396 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r5] 5.Fizazi K, Tran N, Fein L, et al. ; LATITUDE Investigators . Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352-360. doi: 10.1056/NEJMoa1704174 [DOI] [PubMed] [Google Scholar]

[zoi241364r6] 6.Fizazi K, Tran N, Fein L, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019;20(5):686-700. doi: 10.1016/S1470-2045(19)30082-8 [DOI] [PubMed] [Google Scholar]

[zoi241364r7] 7.Chi KN, Protheroe A, Rodríguez-Antolín A, et al. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018;19(2):194-206. doi: 10.1016/S1470-2045(17)30911-7 [DOI] [PubMed] [Google Scholar]

[zoi241364r8] 8.James ND, de Bono JS, Spears MR, et al. ; STAMPEDE Investigators . Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377(4):338-351. doi: 10.1056/NEJMoa1702900 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r9] 9.James ND, Clarke NW, Cook A, et al. ; STAMPEDE Trials Collaborative Group . Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer. 2022;151(3):422-434. doi: 10.1002/ijc.34018 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r10] 10.Chi KN, Agarwal N, Bjartell A, et al. ; TITAN Investigators . Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381(1):13-24. doi: 10.1056/NEJMoa1903307 [DOI] [PubMed] [Google Scholar]

[zoi241364r11] 11.Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39(20):2294-2303. doi: 10.1200/JCO.20.03488 [DOI] [PubMed] [Google Scholar]

[zoi241364r12] 12.Agarwal N, McQuarrie K, Bjartell A, et al. ; TITAN Investigators . Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2019;20(11):1518-1530. doi: 10.1016/S1470-2045(19)30620-5 [DOI] [PubMed] [Google Scholar]

[zoi241364r13] 13.Davis ID, Martin AJ, Stockler MR, et al. ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group . Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381(2):121-131. doi: 10.1056/NEJMoa1903835 [DOI] [PubMed] [Google Scholar]

[zoi241364r14] 14.Armstrong AJ, Azad AA, Iguchi T, et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2022;40(15):1616-1622. doi: 10.1200/JCO.22.00193 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r15] 15.Smith MR, Hussain M, Saad F, et al. ; ARASENS Trial Investigators . Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386(12):1132-1142. doi: 10.1056/NEJMoa2119115 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r16] 16.Fizazi K, Foulon S, Carles J, et al. ; PEACE-1 Investigators . Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022;399(10336):1695-1707. doi: 10.1016/S0140-6736(22)00367-1 [DOI] [PubMed] [Google Scholar]

[zoi241364r17] 17.Sweeney CJ, Martin AJ, Stockler MR, et al. ; ENZAMET Trial Investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group . Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(4):323-334. doi: 10.1016/S1470-2045(23)00063-3 [DOI] [PubMed] [Google Scholar]

[zoi241364r18] 18.Cornford P, Tilki D, van den Bergh RCN, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. European Association of Urology . April 2024. Accessed April 10, 2024. https://d56bochluxqnz.cloudfront.net/documents/full-guideline/EAU-EANM-ESTRO-ESUR-ISUP-SIOG-Guidelines-on-Prostate-Cancer-2024_2024-04-09-132035_ypmy.pdf

[zoi241364r19] 19.Fizazi K, Gillessen S; ESMO Guidelines Committee . Updated treatment recommendations for prostate cancer from the ESMO Clinical Practice Guideline considering treatment intensification and use of novel systemic agents. Ann Oncol. 2023;34(6):557-563. doi: 10.1016/j.annonc.2023.02.015 [DOI] [PubMed] [Google Scholar]

[zoi241364r20] 20.Lowrance W, Dreicer R, Jarrard DF, et al. Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023). J Urol. 2023;209(6):1082-1090. doi: 10.1097/JU.0000000000003452 [DOI] [PubMed] [Google Scholar]

[zoi241364r21] 21.Virgo KS, Rumble RB, Talcott J. Initial management of noncastrate advanced, recurrent, or metastatic prostate cancer: ASCO Guideline update. J Clin Oncol. 2023;41(20):3652-3656. doi: 10.1200/JCO.23.00155 [DOI] [PubMed] [Google Scholar]

[zoi241364r22] 22.Freedland SJ, Agarwal N, Ramaswamy K, et al. Real-world utilization of advanced therapies and racial disparity among patients with metastatic castration-sensitive prostate cancer (mCSPC): a Medicare database analysis. Abstract presented at: 2021 American Society of Clinical Oncology Annual Meeting I; May 28, 2021. Abstract 5073.

[zoi241364r23] 23.Freedland SJ, Sandin R, Sah J, et al. Treatment patterns and survival in metastatic castration-sensitive prostate cancer in the US Veterans Health Administration. Cancer Med. 2021;10(23):8570-8580. doi: 10.1002/cam4.4372 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r24] 24.Freedland SJ, Sandin R, Tagawa ST, et al. 609P Treatment patterns and overall survival (OS) in metastatic castration-sensitive prostate cancer (mCSPC) from 2006 to 2019. Ann Oncol. 2021;32(suppl 5):S650-S651. doi: 10.1016/j.annonc.2021.08.1122 [DOI] [Google Scholar]

[zoi241364r25] 25.George DJ, Agarwal N, Ramaswamy K, et al. 616P Real-world utilization of advanced therapies by metastatic site and age among patients with metastatic castration-sensitive prostate cancer (mCSPC): a Medicare database analysis. Ann Oncol. 2021;32(suppl 5):S655-S656. doi: 10.1016/j.annonc.2021.08.1129 [DOI] [Google Scholar]

[zoi241364r26] 26.George DJ, Agarwal N, Rider JR, et al. Real-world treatment patterns among patients diagnosed with metastatic castration-sensitive prostate cancer (mCSPC) in community oncology settings. Abstract presented at: 2021 American Society of Clinical Oncology Annual Meeting I; May 28, 2021. Abstract 5074.

[zoi241364r27] 27.Ryan CJ, Ke X, Lafeuille MH, et al. Management of patients with metastatic castration-sensitive prostate cancer in the real-world setting in the United States. J Urol. 2021;206(6):1420-1429. doi: 10.1097/JU.0000000000002121 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r28] 28.Swami U, Hong A, El-Chaar NN, et al. Real-world first-line (1L) treatment patterns in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a U.S. health insurance database. Abstract presented at: 2021 American Society of Clinical Oncology Annual Meeting I; May 28, 2021; virtual. Abstract 5072.

[zoi241364r29] 29.Swami U, Sinnott JA, Haaland B, et al. Treatment pattern and outcomes with systemic therapy in men with metastatic prostate cancer in the real-world patients in the United States. Cancers (Basel). 2021;13(19):4951. doi: 10.3390/cancers13194951 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r30] 30.Swami U, Hong A, El-Chaar NN, et al. Underutilization of standard of care (SOC) treatment intensification in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) by specialty. Abstract presented at: 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 16, 2022; San Francisco, CA. Abstract 183.

[zoi241364r31] 31.Swami U, Hong A, El-Chaar NN, et al. The role of physician specialty in the underutilization of standard-of-care treatment intensification in patients with metastatic castration-sensitive prostate cancer. J Urol. 2023;209(6):1120-1131. doi: 10.1097/JU.0000000000003370 [DOI] [PubMed] [Google Scholar]

[zoi241364r32] 32.Tagawa ST, Sandin R, Sah J, Mu Q, Freedland SJ. 679P Treatment patterns of metastatic castration-sensitive prostate cancer (mCSPC): a real-world evidence study. Ann Oncol. 2020;31(suppl 4):S541-S542. doi: 10.1016/j.annonc.2020.08.938 [DOI] [Google Scholar]

[zoi241364r33] 33.Heath EI, Dyson GE, Cackowski FC, Hafron J, Powell I. Treatment intensification patterns and utilization in patients with metastatic castration-sensitive prostate cancer. Clin Genitourin Cancer. 2022;20(6):524-532. doi: 10.1016/j.clgc.2022.06.017 [DOI] [PubMed] [Google Scholar]

[zoi241364r34] 34.Barata PC, Leith A, Ribbands A, et al. Real-world treatment patterns among patients with metastatic castration-resistant prostate cancer: results from an international study. Oncologist. 2023;28(9):e737-e747. doi: 10.1093/oncolo/oyad046 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r35] 35.Leith A, Ribbands A, Kim J, et al. Impact of next-generation hormonal agents on treatment patterns among patients with metastatic hormone-sensitive prostate cancer: a real-world study from the United States, five European countries and Japan. BMC Urol. 2022;22(1):33. doi: 10.1186/s12894-022-00979-9 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r36] 36.Gonzalez JM, Ganguli A, Morgans AK, et al. Discrete-choice experiment to understand the preferences of patients with hormone-sensitive prostate cancer in the USA, Canada, and the UK. Patient. 2023;16(6):607-623. doi: 10.1007/s40271-023-00638-7 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r37] 37.Code of Conduct and Adverse Event Reporting Guidelines. European Pharmaceutical Market Research Association (EPHMRA) . Updated 2021. Accessed August 18, 2022. https://www.ephmra.org/code-conduct-aer

[zoi241364r38] 38.Office for Civil Rights Privacy Brief. Summary of the HIPAA Privacy Rule. US Department of Health and Human Services . Updated May 2003. Accessed August 18, 2022. http://www.hhs.gov/sites/default/files/privacysummary.pdf

[zoi241364r39] 39.Health Information Privacy. HITECH Act Enforcement Interim Final Rule. US Department of Health and Human Services . June 16, 2017. Accessed August 18, 2022. https://www.hhs.gov/hipaa/for-professionals/special-topics/hitech-act-enforcement-interim-final-rule/index.html

[zoi241364r40] 40.Zou H, Hastie T. Regularization and variable selection via the elastic net. J R Stat Soc Series B Stat Methodol. 2005;67(2):301-320. doi: 10.1111/j.1467-9868.2005.00503.x [DOI] [Google Scholar]

[zoi241364r41] 41.Stockler MR, Martin AJ, Davis ID, et al. ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) . Health-related quality of life in metastatic, hormone-sensitive prostate cancer: ENZAMET (ANZUP 1304), an international, randomized phase III trial led by ANZUP. J Clin Oncol. 2022;40(8):837-846. doi: 10.1200/JCO.21.00941 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r42] 42.Stenzl A, Dunshee C, De Giorgi U, et al. Effect of enzalutamide plus androgen deprivation therapy on health-related quality of life in patients with metastatic hormone-sensitive prostate cancer: an analysis of the ARCHES randomised, placebo-controlled, phase 3 study. Eur Urol. 2020;78(4):603-614. doi: 10.1016/j.eururo.2020.03.019 [DOI] [PubMed] [Google Scholar]

[zoi241364r43] 43.Loeb S, Agarwal N, El-Chaar NN, et al. Barriers and facilitators to first-line (1L) treatment intensification (TI) in metastatic castration-sensitive prostate cancer (mCSPC): the IMPLEMENT study. Abstract presented at: 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium; January 29, 2024; San Francisco, CA. Abstract 224.

[zoi241364r44] 44.Choueiri TK, Xie W, D’Amico AV, et al. Time to prostate-specific antigen nadir independently predicts overall survival in patients who have metastatic hormone-sensitive prostate cancer treated with androgen-deprivation therapy. Cancer. 2009;115(5):981-987. doi: 10.1002/cncr.24064 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r45] 45.Matsubara N, Chi KN, Özgüroğlu M, et al. Correlation of prostate-specific antigen kinetics with overall survival and radiological progression-free survival in metastatic castration-sensitive prostate cancer treated with abiraterone acetate plus prednisone or placebos added to androgen deprivation therapy: post hoc analysis of phase 3 LATITUDE study. Eur Urol. 2020;77(4):494-500. doi: 10.1016/j.eururo.2019.11.021 [DOI] [PubMed] [Google Scholar]

[zoi241364r46] 46.Briones J, Khan M, Sidhu AK, Zhang L, Smoragiewicz M, Emmenegger U. Population-based study of docetaxel or abiraterone effectiveness and predictive markers of progression free survival in metastatic castration-sensitive prostate cancer. Front Oncol. 2021;11:658331. doi: 10.3389/fonc.2021.658331 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r47] 47.Fujimoto N, Shiota M, Matsukawa T, et al. Three-month prostate-specific antigen level after androgen deprivation therapy predicts survival in patients with metastatic castration-sensitive prostate cancer. In Vivo. 2021;35(2):1101-1108. doi: 10.21873/invivo.12355 [DOI] [PMC free article] [PubMed] [Google Scholar]

[zoi241364r48] 48.Iacovelli R, Ciccarese C, Caffo O, et al. The role of fast and deep PSA response in castration-sensitive prostate cancer. Anticancer Res. 2022;42(1):165-172. doi: 10.21873/anticanres.15470 [DOI] [PubMed] [Google Scholar]

[zoi241364r49] 49.Hussain M, Tangen CM, Higano C, et al. ; Southwest Oncology Group Trial 9346 (INT-0162) . Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol. 2006;24(24):3984-3990. doi: 10.1200/JCO.2006.06.4246 [DOI] [PubMed] [Google Scholar]

PERMALINK

Physician Reasons for or Against Treatment Intensification in Patients With Metastatic Prostate Cancer

Neeraj Agarwal, MD

Daniel J George, MD

Zachary Klaassen, MD

Rickard Sandin, PhD

Jake Butcher, BSc

Amanda Ribbands, BSc

Liane Gillespie-Akar, MS

Birol Emir, PhD

David Russell, MD

Agnes Hong, PharmD

Krishnan Ramaswamy, PhD

Stephen J Freedland, MD

Key Points

Question

Findings

Meaning

Abstract

Importance

Objective

Design, Setting, and Participants

Main Outcomes and Measures

Results

Conclusions and Relevance

Introduction

Methods

Data Source

ARW Survey Inclusion Criteria

Statistical Analysis

Results

Demographics and Clinical Characteristics

Table 1. Demographic and Clinical Characteristics of Patients With mCSPC Treated by US-Based Physicians by First-Line TIa.

mCSPC Treatment Patterns

Table 2. Treatment Received for mCSPC.

Bivariate Analysis of Physician-Reported Reasons for First-Line mCSPC Treatment Choice

Figure 1. Most Frequently Cited Physician-Reported Reasons for First-Line Treatment Decisions.

Physician-Reported PSA Reduction Goals

Table 3. Physician-Reported PSA Reduction Goals in mCSPC and Likelihood of Receiving TIa.

Multivariable Analysis

Figure 2. Multivariable Analysis of Physician-Reported Reasons and Patient Characteristics Associated With Likelihood of Treatment Intensification (TI).

Discussion

Limitations

Conclusions

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases

Table 1. Demographic and Clinical Characteristics of Patients With mCSPC Treated by US-Based Physicians by First-Line TI^a.

Table 3. Physician-Reported PSA Reduction Goals in mCSPC and Likelihood of Receiving TI^a.