Visual Abstract
Keywords: [177Lu]Lu-PSMA-617, LuPSMA, liver metastases, PSMA-targeted radiopharmaceuticals, metastatic castration-resistant prostate cancer, mCRPC
Abstract
It is well known that patients with liver metastasis from metastatic castration-resistant prostate cancer have poor or only transient responses to many forms of systemic therapy. Data on outcomes after treatment with [177Lu]Lu-PSMA-617 (LuPSMA) are scarce. The VISION trial reports a hazard ratio for overall survival (OS) in the subgroup of patients with liver metastasis without disclosing the absolute duration of survival. Using real-world clinical data, we examined this important subgroup of patients, describing prostate-specific antigen (PSA) response and OS. Methods: A single-institution database was assembled to include all patients receiving LuPSMA at Mayo Clinic in Rochester, Minnesota, for whom treatment was initiated between March 2022 and March 2023. Baseline clinicopathologic and imaging characteristics were abstracted. Patients were then categorized by presence or absence of liver metastasis on pretreatment prostate-specific membrane antigen (PSMA) PET. PSA response and OS for the 2 groups (liver metastasis vs. no liver metastasis) were compared using χ2 testing and the Kaplan–Meier method, respectively. A multivariate Cox regression analysis was performed, including established prognostic factors. Finally, those with pretreatment circulating tumor DNA as determined in an 83-gene panel were assessed for the presence of pathogenic and likely pathogenic alterations. These findings were summarized using descriptive statistics and compared between the 2 cohorts using the Fisher exact test. Results: The overall cohort consisted of 273 patients, including 43 (15.75%) with liver metastasis on pretreatment PSMA PET/CT. The median number of cycles received was 3 (range, 1–6) for patients with liver metastasis and 5 (range, 1–6) for those without hepatic involvement. The 50% or greater reduction in PSA from baseline response rate was lower for those with liver metastasis than for those without (30.23% [13/43] vs 49.77% [106/213], P = 0.019). At a median follow-up of 10 mo (interquartile range, 9–13 mo), there was a significant difference in median OS (8.35 mo vs. not reached, P < 0.001). On multivariate analysis, the presence of liver metastasis was independently associated with shorter survival (hazard ratio, 4.06; P < 0.001). Conclusion: Our data suggest that the presence of liver metastasis predicts poorer outcomes in patients receiving LuPSMA treatment. Alternative and combination approaches should be explored to maximize the antitumor activity of radiopharmaceutical therapy in the liver.
Liver metastasis in prostate cancer commonly emerges later in the disease course and is particularly challenging to manage (1,2). Most systemic therapies, including androgen receptor–targeted agents and chemotherapy, induce limited responses or provide only a modest duration of disease control (3–12). As novel treatments emerge, differential efficacy in clinically important subgroups, such as those with liver metastasis, must be further explored.
[177Lu]Lu-PSMA-617 (LuPSMA) is a radiopharmaceutical therapy granted Food and Drug Administration approval for metastatic castration-resistant prostate cancer (mCRPC) after disease progression on an androgen receptor pathway inhibitor and chemotherapy (13). This particular treatment modality works by delivering β-particles to prostate-specific membrane antigen (PSMA)–positive prostate cancer cells. In the phase III VISION trial, LuPSMA extended median overall survival (OS) by 4 mo in a cohort of men with highly treatment-refractory mCRPC (14).
Subgroup analysis of VISION suggests that certain populations may benefit less (if at all) from treatment. In this article, we aim to use real-world clinical data to provide more granular estimates of LuPSMA efficacy in men with mCRPC and liver metastasis.
MATERIALS AND METHODS
We performed a single-institution retrospective analysis including all patients receiving LuPSMA at Mayo Clinic Rochester, Minnesota, who initiated treatment between March 2022 and March 2023. Clinical data were abstracted from the electronic health record (Epic Systems) at Mayo Clinic. The participants authorized use of their medical records for research purposes (Mayo Clinic Medical Records and Medical Research Authorization). The protocol was reviewed and approved by the Mayo Clinic Institutional Review Board (22-010856), and the requirement to obtain explicit informed consent was waived. All patients not providing research authorization were excluded from these analyses.
Doctorate-level research fellows abstracted pretreatment data, including demographics, disease characteristics, prior treatment details, laboratory values, genomic information, and baseline imaging characteristics, as reported by board-certified nuclear medicine physicians and radiologists. The imaging agent for PSMA PET/CT was either 68Ga-PSMA-11 or 18F-DCFPyL. When available, additional conventional imaging (MRI or CT) was used to clarify ambiguity or indeterminate findings on the pretreatment PSMA PET/CT. With rare exception, our institution considers a patient a favorable candidate for LuPSMA if the molecular imaging PSMA expression score is 2 or greater, which indicates lesion uptake higher than the mean liver uptake. As such, our liver metastasis cohort consisted primarily of patients with PSMA-expressing tumors; thus, patients with liver tumors exhibiting low or absent PSMA expression were not well represented within this cohort.
All pretreatment PSMA PET/CT images at Mayo Clinic were initially interpreted by a board-certified nuclear medicine physician. Standard-of-care radiology reports were used to identify the cohort of patients with suspected liver metastasis. Then, exclusively for the cohort of patients with concerning hepatic lesions, a nuclear medicine research fellow rereviewed each pretreatment PSMA PET/CT scan to manually distinguish physiologic from lesion uptake. The preliminary contours were then proofed and finalized by a board-certified radiologist. MIM software (MIM Software Inc.) was used for postimaging processing and reporting of the following parameters: number of liver metastases, diameter of liver metastases (presented as the median value of the longest cross-sectional diameter for all lesions within one patient), volume of liver metastases (sum of volumes for all liver lesions within one patient), SUVmax in the liver (the highest SUVmax observed for any lesion within one patient), and SUVmean in the liver (the average SUVmean for each liver lesion within one patient).
Endpoints of interest included best prostate-specific antigen (PSA) response and OS. Best PSA response while on treatment was reported as percentage change from baseline. A patient who received only 1 cycle of treatment was considered a nonresponder, and the best PSA response was categorized as no change from baseline. These data are presented as 0% change on the PSA waterfall plots. PSA response rate and OS for the 2 groups (liver metastasis vs. no liver metastasis) were compared using χ2 testing and the Kaplan–Meier method, respectively. Survival was calculated from the date of the first cycle of LuPSMA. Cox regression analysis was performed to evaluate associations between the presence of liver metastasis (categoric) and OS, after adjustment for other established prognostic factors: Eastern Cooperative Oncology Group performance status (≥2), baseline alkaline phosphatase level (>220 U/L), baseline hemoglobin level (continuous), number of prior lines of therapy (continuous), and osseous involvement (categoric) (15–17). Radiographic endpoints were not analyzed because of the retrospective nature of this project and the varied imaging practices among treating providers within our institution.
In an exploratory analysis of this dataset, those with available pretreatment circulating tumor DNA, determined by Guardant (83-gene panel), were assessed for the presence of pathogenic and likely pathogenic alterations. Patients were included only if genomic profiling was performed within 100 d before the first dose of LuPSMA. The frequency and variety (gene amplifications, fusions, insertions/deletions, copy number deletions and rearrangements, splice site–disrupting events, and single-nucleotide variants) of each alteration are reported. Results are presented for gene alterations found at a prevalence of more than 5% in either the liver-metastasis or no-liver-metastasis cohort. Findings are summarized using descriptive statistics and compared using the Fisher exact test.
RESULTS
Patient Characteristics
The overall cohort consisted of 256 patients after exclusion of 17 who did not provide research authorization. A total of 43 (16.8%) patients had liver metastasis visible on pretreatment PSMA PET/CT, whereas 213 patients (83.2%) had metastatic disease involving other sites, including lymph node (n = 150, 70.4%), bone (n = 178, 83.6%), and other visceral locations (n = 32, 15%). Baseline characteristics are shown in Table 1. The 2 cohorts (i.e., liver metastasis vs. no liver metastasis) were similar in age at the start of treatment, in the timing of metastatic presentation (i.e., synchronous vs. metachronous), and in the median number of prior lines of therapy. Median baseline PSA was numerically higher in the cohort with liver metastasis (12.5 vs. 7.6 ng/mL).
TABLE 1.
Baseline Characteristics of Overall Cohort
| Characteristic | Liver metastasis (n = 43) | No liver metastasis (n = 213) |
|---|---|---|
| Median age (y) | 70 (range, 52–87) | 70 (range, 45–93) |
| Race/ethnicity (n) | ||
| Caucasian | 41 (95.3%) | 208 (97.7%) |
| African American | 1 (2.3%) | 0 |
| Asian | 0 | 3 (1.4%) |
| Hispanic | 0 | 1 (0.5%) |
| Other | 1 (2.3%) | 1 (0.5%) |
| Metastatic presentation (n) | ||
| Synchronous | 19 (44.2%) | 79 (37.1%) |
| Metachronous | 24 (55.8%) | 134 (62.9) |
| Gleason score at diagnosis (n) | ||
| ≤7 | 15 (34.9%) | 80 (37.6%) |
| ≥8 | 24 (55.8%) | 115 (54%) |
| Unknown | 4 (9.3%) | 18 (8.4%) |
| ECOG performance status (n) | ||
| 0–1 | 36 (83.7%) | 195 (91.5%) |
| ≥2 | 7 (16.3%) | 18 (8.5%) |
| Median PSA (ng/mL) | 12.5 (IQR, 2.3–129) | 7.6 (IQR, 1.2–64.8) |
| Laboratory parameters | ||
| Median hemoglobin (g/dL) | 11.1 (IQR, 10–12.7) | 12.2 (IQR, 10.9–13.2) |
| Median alkaline phosphatase (U/L) | 102 (IQR, 79–207) | 94 (IQR, 67–129) |
| Median total bilirubin (mg/dL) | 0.4 (IQR, 0.3–0.6) | 0.4 (IQR, 0.3–0.6) |
| Median aspartate aminotransferase (U/L) | 27 (IQR, 21–45) | 21 (IQR, 18–28) |
| Median alanine aminotransferase (U/L) | 19 (IQR, 15–29) | 18 (IQR, 13–25) |
| Median albumin (g/dL) | 4 (IQR, 3.8–4.3) | 4.2 (IQR, 4–4.4) |
| Metastatic distribution (n) | ||
| Lymph node | 36 (83.7%) | 150 (70.4%) |
| Bone | 32 (74.4%) | 178 (83.6%) |
| Viscera | 43 (100%) | 32 (15%) |
| Median no. of prior lines of therapy (n) | 4 (range, 2–9) | 4 (range, 1–10) |
| Median no. of cycles of LuPSMA (n) | 3 (range, 1–6) | 5 (range, 1–6) |
ECOG = Eastern Cooperative Oncology Group.
Within the liver metastasis cohort (n = 43), there were 37 patients with baseline PSMA PET/CT images still available at our institution for further processing. Their baseline imaging characteristics are shown in Table 2. Nearly half (46%) the cohort had 4 or more liver metastases at the time of starting treatment. Lesion-level analysis of the liver metastases revealed a median SUVmean of 7.5 (interquartile range [IQR], 5.4–8.9) and a median SUVmax of 16.1 (IQR, 11.1–23.1). All patients were judged to have a molecular imaging PSMA score of 2–3.
TABLE 2.
Baseline PSMA PET/CT Imaging Characteristics for Subgroup with Liver Metastasis (n = 37)
| Characteristic | Data |
|---|---|
| Number of liver lesions | |
| 1–3 | 20 (54.1) |
| 4–9 | 11 (29.7) |
| 10+ | 6 (16.2) |
| Longest cross-sectional diameter* (mm) | 29 (23.4–38.6) |
| Volume of liver metastases (cm3) | 49.4 (12.2–189.6) |
| Liver SUVmean | 7.5 (5.4–8.9) |
| Liver SUVmax | 16.1 (11.1–23.1) |
| Molecular imaging PSMA score | |
| 2 | 5 (13.5) |
| 3 | 32 (86.5) |
Assessing all individual liver lesions within single patient.
Liver SUVmean: average of SUV means for each liver lesion within one patient, liver SUVmax: highest SUVmax observed for any lesion within one patient.
Qualitative data are number and percentage; continuous data are median and IQR.
Efficacy of LuPSMA in Those with Liver Metastasis
At the time of this analysis, median follow-up was 10 mo (IQR, 9–13 mo) from the start of treatment. The median number of cycles was 3 (range, 1–6) and 5 (range, 1–6) (P < 0.001) for the liver-metastasis and no-liver-metastasis cohorts, respectively. Within the liver-metastasis cohort, 9 (20.9%) patients received only 1 cycle of therapy before treatment discontinuation or death, as compared with 7 (3.3%) patients in the cohort without liver metastasis.
The 50% or greater reduction in PSA from baseline (PSA50) response rate was lower for those with liver metastasis than for those without (30.23% [13/43] vs. 49.77% [106/213], P = 0.019) (Table 3). A PSA waterfall plot is shown in Figure 1. Median OS was also shorter for those with liver metastasis (8.35 mo vs. not reached, P < 0.001) (Fig. 2). A multivariable model including known prognostic variables—Eastern Cooperative Oncology Group performance status (≥2), baseline alkaline phosphatase (>220 U/L), baseline hemoglobin (continuous), number of prior lines of therapy (continuous), and osseous involvement (categoric)—was constructed (Table 4). The presence of liver metastasis was independently associated with shorter OS (hazard ratio, 4.06; P <0.001). In a post hoc analysis, OS was assessed in patients who were sorted by baseline number of hepatic metastases (1–3 or 4–9 vs. 10+), with no clear difference in survival observed (P = 0.968). Survival was also compared in patients categorized by a baseline liver SUVmean of less than 8 (n = 22) versus 8 or higher (n = 15), with numerically longer survival for patients with a higher liver SUVmean (median OS, 7.27 vs. 11.21 mo; P = 0.242).
TABLE 3.
Best PSA Response
| Parameter | Rising PSA (n) | PSA30 response (n) | PSA50 response (n) | PSA90 response (n) |
|---|---|---|---|---|
| Liver metastasis (n = 43) | 10/43 (23.3%) | 15/43 (34.9%) | 13/43 (30.2%) | 7/43 (16.3%) |
| No liver metastasis (n = 213) | 40/213 (18.8%) | 129/213 (60.6%) | 106/213 (49.8%) | 39/213 (18.3%) |
| P | 0.499 | 0.002 | 0.019 | 0.752 |
PSA30 = 30% or greater reduction in PSA from baseline; PSA90 = 90% or greater reduction in PSA from baseline.
FIGURE 1.
Waterfall plots of best PSA response.
FIGURE 2.
Kaplan–Meier curve for OS. NR = not reached; NE = not estimable.
TABLE 4.
Multivariable Cox Regression Model of OS
| Parameter | HR | 95% CI | P |
|---|---|---|---|
| Hemoglobin at start of LuPSMA (continuous) | 0.76 | 0.66–0.87 | <0.001 |
| Alkaline phosphatase at start of LuPSMA > 220 U/L | 3.49 | 2.07–5.88 | <0.001 |
| Number of prior lines of therapy | 1.01 | 0.89–1.15 | 0.883 |
| ECOG performance status ≥ 2 | 3.52 | 1.99–6.24 | <0.001 |
| Presence of liver metastasis | 4.06 | 2.44–6.75 | <0.001 |
| Presence of bony metastasis | 5.19 | 1.85–14.61 | 0.002 |
HR = hazard ratio; ADT = androgen deprivation therapy; ECOG = Eastern Cooperative Oncology Group.
Genomic Profiling via Circulating Tumor DNA
Baseline circulating tumor DNA within 100 d of the start of treatment was available for 22 patients with liver metastasis and 163 patients without liver metastasis. The most common pathogenic and likely pathogenic alterations are summarized in Table 5. In either cohort, alterations of 16 genes (on the 83-gene panel) were found at a prevalence of more than 5%: APC, AR, ATM, BRAF, BRCA2, CHEK2, EGFR, KIT, NF1, NOTCH1, PIK3CA, PTEN, RB1, ROS1, TERT, and TP53. Alterations in the following genes were enriched among patients with liver metastasis (Table 5): ATM (10/22 [45%] vs. 30/163 [18%], P = 0.01), PTEN (3/22 [14%] vs. 2/163 [1%], P = 0.013), and ROS1 (3/22 [14%] vs. 4/163 [2%], P = 0.037).
TABLE 5.
Alterations by Circulating Tumor DNA Analysis
| Liver metastasis (n = 22) | No liver metastasis (n = 163) | ||||
|---|---|---|---|---|---|
| Gene | N (%) | Most common variety of alterations (n) | N (%) | Most common variety of alterations (n) | P |
| APC | 4 (18.2) | FS (2) | 10 (6.1) | FS (4), NON (4) | 0.067 |
| AR | 8 (36.4) | AMP (7) | 58 (35.6) | AMP (38), MIS (25) | 1 |
| ATM | 10 (45.5) | MIS (5), CNL (3) | 30 (18.4) | MIS (16), NON (9) | 0.01 |
| BRAF | 3 (13.6) | AMP (2) | 5 (3.1) | AMP (2), FUS (2) | 0.055 |
| BRCA2 | 6 (27.3) | CNL (4) | 23 (14.1) | FS (12), CNL (7) | 0.122 |
| CHEK2 | 6 (27.3) | MIS (2), CNL (2) | 34 (20.9) | FS (12), MIS (9), CNL (8) | 0.581 |
| EGFR | 2 (9.1) | AMP (2) | 26 (16) | AMP (14), MIS (13) | 0.537 |
| KIT | 1 (4.6) | AMP (1) | 12 (7.4) | MIS (8), AMP (3) | 1 |
| NF1 | 1 (4.6) | FS (1) | 13 (8) | FS (7), NON (3) | 1 |
| NOTCH1 | 3 (13.6) | MIS (3) | 7 (4.3) | FS (3), MIS (2) | 0.101 |
| PIK3CA | 0 | 13 (8) | MIS (8), AMP (4) | 0.371 | |
| PTEN | 3 (13.6) | FS (3) | 2 (1.2) | FS (1), DEL (1) | 0.013 |
| RB1 | 3 (13.6) | FS (2) | 5 (3.1) | NON (2), FS (1) | 0.055 |
| ROS1 | 3 (13.6) | MIS (2) | 4 (2.5) | MIS (3) | 0.037 |
| TERT | 3 (13.6) | Promoter SNV (3) | 8 (4.9) | Promoter SNV (7) | 0.128 |
| TP53 | 10 (45.5) | MIS (9), FS (2) | 89 (54.6) | MIS (73), NON (18), FS (15) | 0.497 |
FS = frameshift mutation; NON = nonsense mutation; AMP = amplification; MIS = missense mutation; CNL = copy number loss; FUS = fusion; DEL = deletion; promoter SNV = promoter region single-nucleotide variant.
DISCUSSION
Effective therapies for prostate cancer liver metastasis remain elusive. A prespecified analysis of OS from the phase III VISION trial suggested comparably less activity of LuPSMA in the subgroup of patients with liver metastasis (hazard ratio, 0.87; 95% CI, 0.53–1.43) without providing more granular estimates of efficacy (14). In this analysis, we use real-world clinical data to further clarify the effectiveness of LuPSMA in this patient population, identifying a higher probability of treatment failure and an overall guarded prognosis.
In the current analysis, we report that patients with liver metastasis were less likely to complete all 6 planned cycles of LuPSMA. Further, median OS was less than 8.5 mo, and whereas these results are disappointing, they are in keeping with the performance of other forms of systemic therapy in the setting of liver metastasis. For instance, COU-AA-301 enrolled men with mCRPC after disease progression on taxane chemotherapy, randomizing patients to abiraterone acetate versus placebo. Patients with liver metastasis had a PSA response rate of only 13.5% and median OS of 7.3 mo (3). In AFFIRM, a study of enzalutamide in a similar patient population, the PSA50 response rate was 35.1% and median OS was 9 mo (18). Finally, approved chemotherapies, such as cabazitaxel with or without carboplatin, may induce a radiographic response in 20%–30% of patients with measurable visceral disease, but OS is limited (19). Though our analysis demonstrated that patients with liver metastasis have generally poor survival, there is still a small subgroup of patients who achieve PSA50 (and even 90% or greater reduction in PSA from baseline) responses, who may still derive clinical benefit from LuPSMA, a well-tolerated systemic therapy.
The arrival of novel radiopharmaceuticals brought hope that LuPSMA would more meaningfully improve oncologic outcomes in this hard-to-treat patient population through targeted delivery of treatment to the liver metastasis. Unfortunately, our results suggest that current forms of radiopharmaceutical therapy still have limited activity in this clinical context, and novel approaches are needed. Our findings are similar to those reported in another small series of patients with hepatic involvement (n = 28) receiving LuPSMA, who had survival of less than 1 y (20). In the current analysis and others, the presence of liver metastasis is independently associated with shorter OS (15). Indeed, Gafita et al. developed nomograms to divide patients receiving LuPSMA into low- and high-risk groups. After calibration, liver involvement was found to be the single most impactful variable on survival (and on the odds of PSA50 response), which is similar to our findings (21). In our cohort, we did observe numerically longer survival in patients with higher SUVmean in the liver, noting that the small sample size precludes definitive conclusions.
Several factors may contribute to the limited activity of LuPSMA in the liver, such as suboptimal tissue penetration and dosimetry, intrinsic radioresistance, and tumor heterogeneity. An exploratory analysis of our dataset has identified important differences in the genomic profiles of patients harboring liver metastasis, which may play a part in the high rates of treatment failure; our findings and the results of others point to an enrichment in alterations impacting homologous recombination repair and tumor suppressor genes (22). However, the limited power for such genomic analyses should be noted and findings interpreted with caution. Areas of future research in the use of radiopharmaceuticals to treat liver metastasis may include exploring higher-dose therapy (perhaps through hepatic artery infusion), adding evaluations of radioembolization with 90Y microspheres (23), using combination approaches with poly(adenosine diphosphate ribose) polymerase inhibitors or immunotherapy (24,25), or using more ionizing targeted α-therapies (26–28).
Our study had several limitations, including its retrospective design, the limited sample size, and the lack of radiographic response assessment. Acknowledging these limitations, we highlight the value of a better understanding of clinical factors, such as the distribution of metastatic disease, that correlate with the outcomes of novel therapies. Such simple, radiographic data are available for every patient at the start of treatment at no extra cost. These data may help providers better sequence therapies and may empower patients with more accurate prognostic estimates. It remains critical to continue investigating additional parameters, such as baseline circulating tumor DNA fraction, which has emerged as a predictive biomarker for differential response to LuPSMA (29).
CONCLUSION
This study fills a void left by phase III clinical trial data and provides granular estimates of survival for important subsets of patients receiving LuPSMA. The presence of liver metastasis independently predicts inferior survival.
DISCLOSURE
This work was supported by the Mayo Clinic CTSA through grant UL1TR002377 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Oliver Sartor holds stock and has other ownership interests in Abbvie, Cardinal Health, Clarity Pharmaceuticals, Convergent Therapeutics, Fusion Pharmaceuticals, Lilly, Ratiopharm, Telix Pharmaceuticals, and United Health Group; receives honoraria from Lantheus Medical Imaging; has a consulting or advisory role with Advanced Accelerator Applications, Amgen, ARTbio, Astellas Pharma, AstraZeneca, Bayer, Blue Earth Diagnostics, Clarity Pharmaceuticals, Fusion Pharmaceuticals, Hengrui Therapeutics, Isotopen Technologien, Janssen, MacroGenics, Medscape, Merck, Northstar, Novartis, Noxopharm, Pfizer, Point Biopharma, Progenics, Ratio, Sanofi, Telix Pharmaceuticals, Tempus, TeneoBio, and Tessa Therapeutics; receives research funding from Advanced Accelerator Applications (to the institution), Amgen (to the institution), AstraZeneca (to the institution), Bayer (to the institution), Endocyte (to the institution), InVitae (to the institution), Janssen, Lantheus Medical Imaging (to the institution), Merck (to the institution), POINT Biopharma, Progenics (to the institution), and Sanofi (to the institution); holds a patent (Koochekpour, Sartor AO, inventors. Saposin C and receptors as targets for treatment of benign and malignant disorders. U.S. patent awarded January 23, 2007; patent 7,166,691); has provided expert testimony for Sanofi; and receives travel and accommodation expenses from AstraZeneca, Bayer, Johnson & Johnson, Lantheus Medical Imaging, Progenics, and Sanofi. Jacob Orme has a consulting or advisory role with NaNotics and holds patents regarding PD-L1 cleavage and immunotherapy resistance in multiple cancers (with the institution as the assignee). Ayse Kendi has a consulting or advisory role with Novartis and receives research funding from Novartis (to the institution). Geoffrey Johnson has a leadership role with Green Clinic and Nucleus RadioPharma (to the institution); has a consulting or advisory role with AstraZeneca (to the institution), Blue Earth Diagnostics (to the institution), Curium Pharma (to the institution), MedTrace (to the institution), MorphImmune (to the institution), Novartis (to the institution), Siemens Healthineers (to the institution), Viewpoint Molecular Targeting (to the institution), and Z-Alpha (to the institution); received research funding from Clarity Pharmaceuticals (to the institution), Clovis Oncology (to the institution), MedTrace (to the institution), Novartis (to the institution), Pfizer (to the institution), and Viewpoint Molecular Targeting (to the institution); and holds patents on radiopharmaceuticals (with the institution as the assignee). Praful Ravi receives research funding from Bayer (to the institution), Lilly (to the institution), and Telix Pharmaceuticals (to the institution). Daniel Childs receives honoraria from Targeted Oncology, IntrinsiQ, MJH Life Sciences, and International Centers for Precision Oncology Foundation; has a consulting or advisory role with Janssen Biotech (to the institution) and Novartis (to the institution); receives research funding from Janssen Biotech (to the institution); and receives travel and accommodation expenses from the Prostate Cancer Foundation. No other potential conflict of interest relevant to this article was reported.
KEY POINTS
QUESTION: How does the presence of liver metastasis impact outcomes in patients with mCRPC treated with LuPSMA?
PERTINENT FINDINGS: In a retrospective cohort study of 273 men with mCRPC treated with LuPSMA, patients with liver metastasis had a significantly lower PSA50 response rate (30.23% vs 49.77%) and shorter OS (8.35 mo vs. not reached) than patients without liver metastasis. Liver metastasis was identified as an independent prognostic factor for worse OS.
IMPLICATIONS FOR PATIENT CARE: Our findings highlight the need for tailored combination approaches and novel treatment strategies for managing liver metastasis in patients with mCRPC.
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