Abstract
Importance:
Patients diagnosed with localized prostate cancer have to decide among treatment strategies that may differ in their likelihood of adverse effects.
Objective:
To compare quality of life (QOL) after radical prostatectomy, external beam radiotherapy and brachytherapy vs. active surveillance.
Design/Setting/Participants:
Population-based prospective cohort of 1,141 men with newly-diagnosed prostate cancer were enrolled from January 2011 through June 2013 in collaboration with the North Carolina Central Cancer Registry (Rapid Case Ascertainment). 57% of eligible men enrolled. Median time from diagnosis to enrollment was 5 weeks, and all men were enrolled with written informed consent prior to treatment. Final follow-up date for current analysis was September 9, 2015.
Exposure:
Treatment – radical prostatectomy, external beam radiotherapy, brachytherapy, or active surveillance.
Main Outcomes and Measures:
Quality of life using the validated instrument Prostate Cancer Symptom Indices was assessed at baseline (pre-treatment), and 3, 12, 24 months after treatment. The instrument contains 4 domains – sexual dysfunction, urinary obstruction and irritation, urinary incontinence, and bowel problems – each scored from 0 (no dysfunction) to 100 (maximum dysfunction). Propensity-weighted mean domain scores were compared between each treatment group vs. active surveillance at each time point.
Results:
314 men pursued active surveillance (27.5%), 249 external beam radiotherapy (21.8%), 109 brachytherapy (9.6%), and 469 radical prostatectomy (41.1%). After propensity weighting, median age was 66-67 years across groups, and 77-80% were white. Propensity-weighted baseline sexual dysfunction scores were 41.8-46.4 across groups, urinary obstruction and irritation 20.8-22.8, urinary incontinence 9.7-10.5, and bowel problems 5.7-6.1. Compared to active surveillance, mean sexual dysfunction scores worsened by 3 months for radical prostatectomy (+36.2 points, 95% CI 30.4-42.0), external beam radiotherapy (+13.9, 95% CI 6.7-21.2) and brachytherapy (+17.1, 95% CI 7.8-26.6) patients. Brachytherapy (+20.5 vs. active surveillance, 95% CI 15.1-25.9) and external beam radiotherapy (+11.7, 95% CI 8.7-14.8) were associated with acute worsening of urinary obstruction and irritation, radical prostatectomy (+33.6, 95% CI 27.8-39.2) with urinary incontinence, and external beam radiotherapy (+4.9, 95% CI 2.4-7.4) bowel symptoms. By 24 months, mean scores between treatment groups vs. active surveillance were not significantly different in most domains.
Conclusions and Relevance:
In this cohort of men with localized prostate cancer, each treatment strategy was associated with distinct patterns of adverse effects over 2 years. These findings should be used to promote treatment decisions that incorporate individual preferences.
Keywords: prostate cancer, comparative effectiveness, quality of life, prostatectomy, radiotherapy, active surveillance
Introduction
The comparative effectiveness of contemporary treatment options for localized prostate cancer is one of the highest priority research questions according to the Institute of Medicine.1 Because prostate cancer patients often have extended life expectancy, the quality of life (QOL) effects of different treatment options is a central consideration for many men in their decision-making process.
Since the mid-2000’s, technologic advances in surgical and radiation treatments – e.g. robotic prostatectomy and intensity-modulated radiotherapy – have been rapidly disseminated in clinical practice.2,3 These new technologies were developed with a primary purpose to reduce treatment-related morbidity rather than improve cure. Studies showed that surgery and radiotherapy can cause sexual, urinary and bowel dysfunction;4 however, it is unclear whether contemporary technologies cause the same magnitude of problems. In addition, with increasing recognition that many patients may not need treatment immediately, active surveillance is now a standard option5 which preserves QOL for an unknown period of time for each man, until treatment is needed at the time of cancer progression.
The North Carolina Prostate cancer Comparative Effectiveness & Survivorship Study (NC ProCESS) is a population-based, observational cohort of men with newly-diagnosed prostate cancer – who were all enrolled prior to treatment and followed prospectively. The purpose of this study was to analyze QOL changes from baseline (pre-treatment) through 2 years after treatment for men who received radical prostatectomy, external beam radiotherapy (RT), or brachytherapy vs. those who pursued active surveillance.
Methods
This study was approved by the University of North Carolina Institution Review Board. Patients were recruited in collaboration with the Rapid Case Ascertainment system of the North Carolina Central Cancer Registry (NCCCR). All participants signed written informed consent. The NCCCR achieves the highest North American Association of Central Cancer Registries standard for complete and accurate cancer incidence data (gold certificate), with >95% data completeness and 100% error-free data on cancer type, sex, race and age. NCCCR does not collect data on adverse effects. Rapid case ascertainment is an accelerated incident reporting process where registry staff proactively obtains information regarding tumors relevant to the study from local hospitals/facilities throughout all 100 counties of the State. This system allowed completion of baseline survey a median of 5 weeks after diagnosis.
Data collection
Demographics – age, race, insurance, education, household income, marital status – were assessed by patient report on baseline survey. Treatments received and dates were determined by medical record abstraction; if medical record was unavailable, then cancer registry data were used. Because the primary goal of this study was to inform patients’ initial treatment decision-making, treatment group assignment for data analysis was based on the initial treatment received; e.g. men who first received a prostatectomy and subsequently received an additional salvage treatment were categorized in the prostatectomy group. Active surveillance was defined with medical records stating this as the plan.
Outcomes
QOL was assessed using the validated Prostate Cancer Symptom Indices (PCSI);6 all surveys were conducted by telephone similar to prior methodology,7 at baseline (pre-treatment), and 3, 12, 24 months after the treatment date. For active surveillance, an anchor date was assigned as 3 months after diagnosis for purposes of calculating subsequent survey dates. Each participant at each time point was called up to 10 times over a 3 week period (including evening and weekend times) to maximize response. Date of the last survey used in the current analysis was September 9, 2015.
The PCSI has 4 domains: urinary obstruction and irritation (5 items), urinary incontinence (3 items), sexual dysfunction (5 items), and bowel problems (6 items). Each domain is scored from 0 to 100, with higher score indicating more/worse dysfunction. Minimal clinically important differences for PCSI domains have not been defined. Parallel to each of the 4 domains are additional questions which ask patients about the magnitude of bother related to urinary obstruction and irritation, urinary incontinence, sexual and bowel symptoms. In addition to numerical scoring for each domain described above, the PCSI has established functional levels (normal, intermediate, and poor) that incorporate the symptom as well as bother questions8,9 – which complement the score reporting because QOL score changes are well-recognized to be difficult for patients and physicians to interpret.10 Normal function describes a patient with essentially no dysfunction or distress in a domain.11,12 For example, normal function in the urinary incontinence domain describes a man who has full urinary control without incontinence. Intermediate function describes a patient with at least one distressful symptom but none very distressful. For example, intermediate urinary incontinence represents leaking only at certain times, and no more than a few drops. Poor function describes patients with at least one very distressful symptom. For example, poor sexual function represents no erections capable of intercourse, or a lot of difficulty getting and keeping an erection. This classification adds clinical meaning to numerical scores, and also allowed analysis of QOL outcomes stratified by each participant’s baseline level.9 Prior work showed that effect sizes between functional levels of the PCSI are large.9,12
Data analysis
To adjust for potentially important differences in baseline characteristics across cohorts, propensity scores (PS) were estimated separately for each of the three treatment types (RT, brachytherapy, and prostatectomy) versus active surveillance. Specifically, PS were obtained from the predicted probabilities in separate logistic regression models contrasting active surveillance against each of the three treatment types. Variables included in the regression models included race, insurance, marital status, education, income, year of diagnosis, age at diagnosis, and baseline SF-12 and PCSI domain scores. Using the PS, all patients in the three treatment groups were assigned weights from their PS odds [PS/(1-PS)] whereas patients in active surveillance each received a weight of 1.15 This methodology balances the observed covariate distribution between the treatment groups relative to active surveillance allowing us to compare each treatment group’s QOL outcomes against active surveillance.13 Standardized differences14 were calculated to compare the distributions of covariates between the cohorts both before and after PS weighting to assess that the covariate balancing adequately addressed measured confounding across cohorts.
Propensity-weighted QOL scores for each PCSI domain was calculated for each participant at each time point. Missing data at 3, 12, and 24 months were multiply imputed using the fully conditional specification approach.15,16 Multiple imputation was separately run for each of four domains within each treatment group for men with non-missing data at baseline. Briefly, this method sequentially regressed an outcome on the immediately preceding outcome (time point) score and baseline characteristics and replaced the missing values with values from observed (non-missing) data that were closest to the model-predicted value for the respective observation. To account for potential non-independence due to weighting, robust standard errors were used in the computation of 95% confidence intervals from the imputed datasets. To account for uncertainty occurring due to imputation, final estimates were derived by pooling estimates from all imputed datasets. Missing QOL functional levels were also imputed using a similar approach. Ordinal logistic regression was used to impute missing levels using the preceding time-point functional level and QOL score and baseline characteristics as variables.
The primary goal of this study was to compare the domain scores of each treatment group (prostatectomy, RT, brachytherapy) against active surveillance. We used an established convention17–19 to denote clinically-meaningful differences in scores as those which exceed ½-standard deviation of the baseline score of the active surveillance (control) group. In addition to analyses of the overall cohort, stratified subgroup analyses based on patients’ baseline QOL level in each domain were performed to assess if treatments differentially affected men who had different levels of baseline QOL.
All statistical tests were two-sided with significance threshold <0.05. Analysis was performed using SAS version 9.4.
Results
From January 2011 through June 2013, 1,419 men with localized prostate cancer and not yet started treatment signed informed consent and were enrolled; this represents 57% participation among eligible men.20 Participants vs. non-participants were younger (median age 65 vs 68), with non-significantly different Gleason scores and race.20 Among enrolled men, 69 did not receive any of the 4 modalities to be compared in this analysis, and an additional 209 did not complete any follow-up survey. Therefore, this analysis included a final sample of 1,141 men.
Among 1,141 men, 314 received active surveillance, 249 RT, 109 brachytherapy, and 469 prostatectomy (Table 1). Among RT, 94.8% received intensity-modulated radiotherapy, and 70.7% with image guidance; 86.6% of prostatectomy was robotic. Participants were socio-demographically diverse in race, education and income. Prostatectomy patients were younger and had better baseline QOL than radiotherapy patients. Differences in baseline demographic characteristics and QOL were minimized with propensity weighting. After propensity weighting, median age was 66-67 across groups, and 77-80% were white.
Table 1 –
Patient demographics and baseline characteristics
| Before Propensity Weighting | After Propensity Weighting | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Active Surveillance | External Beam RT | Brachytherapy | Radical Prostatectomy | Active Surveillance* | External Beam RT | Brachytherapy | Radical Prostatectomy | |||||||||
| N=314 | N=249 | N=109 | N=469 | |||||||||||||
| N | % | N | % | N | % | N | % | % | % | % | % | |||||
| Age at diagnosis, yr | ||||||||||||||||
| Median (std) | 67 (7.3) | 67 (7.1) | 66 (7.3) | 62 (6.8) | 67 (7.3) | 67 (7.3) | 67 (7.6) | 66 (7.3) | ||||||||
| Race | ||||||||||||||||
| White | 242 | 77 | 154 | 62 | 82 | 75 | 347 | 74 | 77 | 79 | 77 | 80 | ||||
| African American | 69 | 22 | 84 | 34 | 26 | 24 | 111 | 24 | 22 | 19 | 20 | 19 | ||||
| Other | 3 | 1 | 11 | 4 | 1 | 1 | 11 | 2 | 1 | 2 | 3 | 2 | ||||
| Health insurance | ||||||||||||||||
| Medicare | 156 | 50 | 134 | 54 | 58 | 53 | 139 | 30 | 50 | 50 | 51 | 51 | ||||
| Private | 94 | 30 | 61 | 25 | 31 | 28 | 246 | 53 | 30 | 30 | 28 | 30 | ||||
| Medicaid/None | 64 | 20 | 54 | 22 | 20 | 18 | 84 | 18 | 20 | 20 | 21 | 19 | ||||
| Education | ||||||||||||||||
| High school or less | 93 | 30 | 99 | 40 | 42 | 38 | 131 | 28 | 30 | 28 | 29 | 29 | ||||
| Some college | 86 | 27 | 71 | 29 | 35 | 32 | 138 | 29 | 27 | 29 | 27 | 27 | ||||
| College graduate | 135 | 43 | 79 | 32 | 32 | 29 | 200 | 43 | 43 | 43 | 44 | 44 | ||||
| Household income | ||||||||||||||||
| <$40,000 | 117 | 37 | 128 | 51 | 51 | 47 | 139 | 30 | 37 | 35 | 36 | 34 | ||||
| $40,000-70,000 | 88 | 28 | 64 | 26 | 35 | 32 | 129 | 28 | 28 | 29 | 32 | 27 | ||||
| >$70,000-90,000 | 44 | 14 | 23 | 9 | 13 | 12 | 69 | 15 | 14 | 15 | 13 | 15 | ||||
| >$90,000 | 65 | 21 | 34 | 14 | 10 | 9 | 132 | 28 | 21 | 20 | 19 | 23 | ||||
| Married | 257 | 82 | 184 | 74 | 93 | 85 | 372 | 79 | 82 | 82 | 79 | 78 | ||||
| Baseline QOL Scores | Mean (std) | Mean (std) | Mean (std) | Mean (std) | Mean (std) | Mean (std) | Mean (std) | Mean (std) | ||||||||
| SF-12 Physical | 48.7 (10.6) | 48.1 (11.0) | 49.9 (9.6) | 51.2 (9.8) | 48.7 (10.6) | 48.8 (11.2) | 48.9 (9.7) | 49.7 (9.9) | ||||||||
| SF-12 Mental | 55.2 (7.7) | 53.1 (9.7) | 54.7 (8.2) | 52.2 (9.5) | 55.2 (7.7) | 55.4 (7.9) | 55.5 (7.9) | 55.5 (7.9) | ||||||||
| PCSI Sexual Dysfunction | 43.4 (37.6) | 51.1 (39.5) | 46.5 (38.7) | 35.6 (36.6) | 43.4 (37.6) | 41.8 (39.5) | 46.4 (40.1) | 41.6 (38.0) | ||||||||
| PCSI Urinary Obs and Irr | 22.8 (13.5) | 23.6 (15.5) | 17.7 (10.2) | 22.9 (14.2) | 22.8 (13.5) | 22.3 (14.8) | 20.8 (10.5) | 22.6 (13.6) | ||||||||
| PCSI Ur Incontinence | 10.4 (20.4) | 13.0 (22.1) | 6.2 (14.8) | 7.9 (16.7) | 10.4 (20.4) | 9.9 (19.7) | 10.5 (20.8) | 9.7 (18.4) | ||||||||
| PCSI Bowel Problems | 5.9 (8.0) | 7.2 (10.7) | 5.0 (7.6) | 5.8 (8.4) | 5.9 (8.0) | 5.7 (8.5) | 6.1 (7.5) | 6.2 (8.0) | ||||||||
| Median(IQR) | Median(IQR) | Median(IQR) | Median(IQR) | Median(IQR) | Median(IQR) | Median(IQR) | Median(IQR) | |||||||||
| SF-12 Physical | 52.5 (44.6-56.1) | 51.8 (41.6-56.1) | 52.6 (46.6-56.4) | 54.8 (47.8-57.5) | 52.5 (44.6-56.1) | 52.6 (43.4-56.4) | 51.2 (43.6-56.4) | 53.1 (44.1-56.7) | ||||||||
| SF-12 Mental | 57.2 (51.2-60.1) | 55.3 (49.0-60.0) | 57.2 (51.8-59.6) | 54.4 (47.8-58.3) | 57.2 (51.2-60.1) | 57.2 (51.7-61.3) | 57.2 (53.2-59.6) | 57.2 (52.6-60.1) | ||||||||
| PCSI Sexual Dysfunction | 33.3 (5.6-83.3) | 44.4 (11.1-94.4) | 38.9 (11.1-88.9) | 22.2 (5.6-77.8) | 33.3 (5.6-83.3) | 27.8 (5.6-88.9) | 33.3 (11.1-88.9) | 27.8 (5.6-83.3) | ||||||||
| PCSI Urinary Obs and Irr | 22.2 (11.1-33.3) | 22.2 (11.1-33.3) | 16.7 (11.1-27.8) | 22.2 (11.1-33.3) | 22.2 (11.1-33.3) | 22.2 (11.1-27.8) | 16.7 (11.1-27.8) | 22.2 (11.1-27.8) | ||||||||
| PCSI Ur incontinence | 0 (0-10.0) | 0 (0-30.0) | 0 (0-0) | 0 (0-0) | 0 (0-10.0) | 0 (0-0.0) | 0 (0-0.0) | 0 (0-10.0) | ||||||||
| PCSI Bowel Problems | 4.2 (0-8.3) | 4.2 (0-8.3) | 4.2 (0-8.3) | 4.2 (0-8.3) | 4.2 (0-8.3) | 4.2 (0-8.3) | 4.2 (0-8.3) | 4.2 (0-12.5) | ||||||||
| Patients with normal baseline QOL function | N (%) | N (%) | N (%) | N (%) | % | % | % | % | ||||||||
| PCSI Sexual Dysfunction | 90 (29.0) | 54 (21.8) | 26 (24.5) | 167 (35.9) | 29.0 | 31.3 | 27.1 | 28.1 | ||||||||
| PCSI Urinary Obs and Irr | 68 (22.3) | 58 (23.5) | 36 (34.3) | 125 (27.1) | 22.3 | 25.9 | 30.7 | 24.1 | ||||||||
| PCSI Ur Incontinence | 226 (73.9) | 169 (69.3) | 86 (81.9) | 360 (78.1) | 73.9 | 76.4 | 75.6 | 74.8 | ||||||||
| PCSI Bowel Problems | 134 (43.2) | 99 (40.1) | 52 (49.1) | 205 (44.3) | 43.2 | 44.3 | 36.6 | 42.4 | ||||||||
| The variables below were not included in propensity score calculation | ||||||||||||||||
| Prostate specific antigen (ng/mL) | ||||||||||||||||
| 0-9.9 | 273 (89.2) | 184 (74.8) | 97 (90.7) | 407 (87.2) | 89.2 | 80.1 | 91.8 | 87.3 | ||||||||
| 10-20 | 19 (6.2) | 35 (14.2) | 8 (7.5) | 40 (8.6) | 6.2 | 11.9 | 6.5 | 7.2 | ||||||||
| >20 | 14 (4.6) | 27 (11.0) | 2 (1.9) | 20 (4.3) | 4.6 | 8.0 | 1.7 | 5.5 | ||||||||
| Biopsy Gleason score | ||||||||||||||||
| ≤ 6 | 268 (86.2) | 88 (35.8) | 84 (79.2) | 213 (45.6) | 86.2 | 39.2 | 72.7 | 46.8 | ||||||||
| 7 | 41 (13.2) | 121 (49.2) | 21 (19.8) | 207 (44.3) | 13.2 | 46.5 | 23.1 | 41.6 | ||||||||
| 8-10 | 2 (0.6) | 37 (15.0) | 1 (0.9) | 47 (10.1) | 0.6 | 14.4 | 4.2 | 11.6 | ||||||||
| Clinical stage | ||||||||||||||||
| T1 | 276 (88.7) | 179 (72.8) | 94 (87.9) | 348 (74.4) | 88.8 | 73.2 | 79.2 | 71.8 | ||||||||
| T2 | 35 (11.3) | 61 (24.8) | 13 (12.1) | 114 (24.4) | 11.3 | 24.9 | 20.8 | 26.8 | ||||||||
| T3/T4 | 0 (0) | 6 (2.4) | 0 (0) | 6 (1.3) | 0 | 1.9 | 0 | 1.5 | ||||||||
Abbreviations: RT, radiotherapy; QOL, quality of life; obs and irr, obstruction and irritation; std, standard deviation; IQR, interquartile range; PCSI, Prostate Cancer Symptom Indices.
Propensity weight for active surveillance was set as 1.
SF-12 Mental and Physical Function: scores range from 0 to 100, with higher score indicating better quality of life.
PCSI domains:6 scores range from 0 to 100, with higher score indicating more symptoms and dysfunction. Minimally clinically important difference is not defined for this instrument.
Missing data in QOL are detailed in eTable 1. At 24 months, there was missing data in 19-29% of participants across groups and QOL domains.
Sexual dysfunction:
Propensity-weighted mean domain scores across the 4 groups at each time point were summarized in Table 2. Sensitivity analysis which included the 209 patients with baseline but no follow-up survey data is shown in eTable. At baseline, propensity-weighted scores were 43.4 (active surveillance, 95% CI 39.2-47.6), 41.8 (RT, 95% CI 36.3-47.2), 46.4 (brachytherapy, 95% CI, 36.1-56.7), and 41.6 (prostatectomy, 95% CI 35.6-47.6). Mean scores for the active surveillance group increased gradually over time. At 3 and 12 months but not 24 months, RT (3 months: +13.9, 95% CI 6.7-21.2; 12 months: +10.2, 95% CI 3.1-17.1) and brachytherapy (3 months: +17.1, 95% CI 7.8-26.6; 12 months: +14.3, 95% CI 4.6-24.0) patients had increased sexual dysfunction compared to active surveillance; however, these differences did not meet threshold for clinical significance. eTable 3 details sexual dysfunction scores in subgroups of patients who received RT alone and RT plus androgen deprivation therapy. Differences between prostatectomy vs. active surveillance met the threshold for clinical significance (3 months: +36.2, 95% CI 30.4-42.0; 12 months: +27.6, 95% CI 21.8-33.4).
Table 2 –
Propensity-weighted PCSI sexual, urinary and bowel domain scores over time across different treatment groups
| Active Surveillance | External Beam RT | Brachytherapy | Radical Prostatectomy | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sexual Dysfunction | N** | Mean (95%CI) | N** | Mean (95%CI) | Mean Diff Score vs. AS (95%CI) | N** | Mean (95%CI) | Mean Diff Score vs. AS (95% CI) | N** | Mean (95%CI) | Mean Diff Score vs. AS (95% CI) |
| Baseline | 310 | 43.4 (39.2-47.6) | 248 | 41.8 (36.3-47.2) | −1.6 (−8.5,5.2) | 106 | 46.4 (36.1-56.7) | 3.0 (−8.1,14.1) | 465 | 41.6 (35.6-47.6) | −1.8 (−9.1,5.5) |
| 3 months | 299 | 44.6 (40.2-48.9) | 229 | 58.5 (52.7-64.2) | 13.9 (6.7,21.2) | 107 | 61.7 (53.4-70.1) | 17.1 (7.8,26.6) | 440 | 80.8 (77.0-84.6) | 36.2 (30.4,42.0)* |
| 12 months | 272 | 48.1 (43.8-52.4) | 215 | 58.2 (52.7-63.7) | 10.2 (3.1,17.1) | 96 | 62.4 (53.9-70.9) | 14.3 (4.6,24.0) | 414 | 75.7 (71.8-79.6) | 27.6 (21.8,33.4)* |
| 24 months | 229 | 56.6 (52.1-61.0) | 187 | 59.2 (53.6-64.7) | 2.6 (−4.8,10.0) | 78 | 61.6 (53.5-69.7) | 5.0 (−4.2,14.2) | 375 | 73.7 (69.2-78.1) | 17.1 (10.9,23.3) |
| Urinary Obs and Irr | |||||||||||
| Baseline | 307 | 22.8 (21.2-24.3) | 248 | 22.3 (20.3-24.4) | −0.5 (−3.0,2.2) | 107 | 20.8 (18.3-23.3) | −2.0 (−4.9,1.0) | 465 | 22.6 (21.1-24.2) | −0.2 (−2.3,2.1) |
| 3 months | 298 | 23.2 (21.7-24.6) | 234 | 34.9 (32.2-37.6) | 11.7 (8.7,14.8)* | 104 | 43.7 (38.4-48.9) | 20.5 (15.1,25.9)* | 431 | 27.3 (25.4-29.1) | 4.1 (1.7,6.5) |
| 12 months | 278 | 26.2 (24.4-27.9) | 217 | 23.9 (21.7-26.1) | −2.3 (−5.1,0.6) | 93 | 31.7 (27.0-36.4) | 5.5 (0.4,10.6) | 417 | 21.9 (20.0-23.7) | −4.3 (−6.9,−1.7) |
| 24 months | 222 | 25.3 (23.5-27.1) | 188 | 23.0 (20.7-25.2) | −2.3 (−5.2,0.6) | 80 | 28.2 (24.4-32.0) | 2.9 (−1.3,7.0) | 376 | 19.6 (17.8-21.4) | −5.7 (−8.2,−3.1) |
| Urinary Incontinence | |||||||||||
| Baseline | 308 | 10.4 (8.2-12.8) | 241 | 9.9 (7.5-12.4) | −0.6 (−3.9,2.8) | 108 | 10.5 (3.8-17.2) | 0 (−7.1,7.1) | 462 | 9.7 (7.2-12.2) | −0.8 (−4.2,2.6) |
| 3 months | 301 | 12.0 (9.7-14.4) | 227 | 15.6 (12.3-19.0) | 3.6 (−0.5,7.7) | 107 | 18.1 (12.5-23.7) | 6.1 (0,12.2) | 406 | 45.6 (40.3-50.8) | 33.6 (27.8,39.2)* |
| 12 months | 276 | 14.1 (11.4-16.7) | 216 | 15.3 (11.9-18.6) | 1.2 (−3.1,5.5) | 95 | 13.9 (8.6-19.3) | −0.2 (−6.2,5.9) | 413 | 32.3 (27.7-36.9) | 18.2 (12.9,23.5)* |
| 24 months | 226 | 17.6 (14.6-20.6) | 190 | 16.6 (13.3-20.0) | −1.0 (−5.5,3.6) | 79 | 15.3 (9.9-20.8) | −2.3 (−8.5,3.9) | 374 | 33.0 (27.2-38.8) | 15.4 (8.9,21.9)* |
| Bowel Problems | |||||||||||
| Baseline | 314 | 5.9 (5.0-6.8) | 246 | 5.7 (4.6-6.7) | −0.2 (−1.6,1.1) | 109 | 6.1 (4.5-7.6) | 0.2 (−1.6,2.0) | 467 | 6.2 (5.2-7.3) | 0.3 (−1.1,1.7) |
| 3 months | 302 | 7.1 (6.0-8.2) | 235 | 12.0 (9.8-14.3) | 4.9 (2.4,7.4)* | 108 | 9.0 (6.9-11.1) | 1.9 (−0.5,4.3) | 444 | 6.7 (5.5-7.8) | −0.4 (−2.0,1.2) |
| 12 months | 279 | 7.2 (6.0-8.4) | 218 | 9.0 (7.3-10.7) | 1.8 (−0.3,3.9) | 96 | 7.0 (5.2-8.8) | −0.2 (−2.4,2.0) | 420 | 5.8 (4.9-6.8) | −1.4 (−2.9,0.2) |
| 24 months | 229 | 6.2 (5.3-7.1) | 190 | 9.9 (7.4-12.4) | 3.7 (1.0,6.4) | 81 | 6.8 (4.9-8.6) | 0.6 (−1.5,2.7) | 379 | 5.2 (4.4-6.0) | −1.0 (−2.2,0.3) |
Abbreviations: PCSI, Prostate Cancer Symptom Indices; RT, radiotherapy; obs and irr, obstruction and irritation; diff, difference.
Missing data were imputed.
PCSI domains:6 scores range from 0 to 100, with higher score indicating more symptoms and dysfunction. Minimally clinically important difference is not defined for this instrument.
denotes clinically meaningful difference (vs. active surveillance) based on exceeding the threshold of ½ standard deviation of the active surveillance baseline score. As reported in Table 1, standard deviation scores were: urinary obstruction/irritation (13.5), urinary incontinence (20.4), bowel problems (8.0), and sexual dysfunction (37.6)
raw (unweighted) numbers of patients with non-missing data.
Among active surveillance patients, 18.7% received treatment within 24 months: 6.2% radical prostatectomy, 6.9% external beam RT, 3.1% brachytherapy, and 2.4% other.
Table 3 summarized propensity-weighted results stratifying participants by baseline sexual function level. For men who reported normal baseline sexual function, 57.1% (propensity-weighted N=46.6/81.6) reported poor function at 24 months after prostatectomy, 27.2% after RT (N=25.5/93.8), 34.2% brachytherapy (N=27.1/79.2), and 25.2% active surveillance (N=22.7/90.1). For men with intermediate baseline function, larger proportions reported poor function at 24 months: 76.9% after prostatectomy (N=69.8/90.8), 55.0% for RT (N=41.8/76.0), 50.6% brachytherapy (N=34.9/69.0), and 45.9% active surveillance (N=37.2/81.0). Men who reported poor baseline sexual function largely remained with poor function at 24 months.
Table 3:
Propensity-weighted sexual, urinary, and bowel function at 24 months by treatment type stratified by baseline function level
| Sexual Dysfunction | |||||
|---|---|---|---|---|---|
| 24 Month Functional Level | |||||
| Normal % (95% CI) | Intermediate % (95% CI) | Poor % (95% CI) | |||
| Baseline Functional Level | Normal | Active surveillance | 44.6 (43.3,45.7) | 30.3 (29.4,31.0) | 25.2 (24.4,26.1) |
| Brachytherapy | 36.2 (34.2,38.5) | 29.6 (27.2,31.9) | 34.2 (32.3,36.0) | ||
| Radical Prostatectomy | 9.4 (9.1,9.8) | 33.5 (32.9,34.0) | 57.1 (56.6,57.6) | ||
| External beam RT | 27.1 (26.2,28.1) | 45.7 (44.5,46.8) | 27.2 (26.6,27.9) | ||
| Intermediate | Active surveillance | 10.2 (9.4,10.9) | 43.9 (43.0,45.0) | 45.9 (45.0,46.7) | |
| Brachytherapy | 2.7 (1.5,3.9) | 46.7 (44.2,49.0) | 50.6 (48.5,53.0) | ||
| Radical Prostatectomy | 5.1 (4.7,5.7) | 18.0 (17.2,18.8) | 76.9 (76.1,77.6) | ||
| External beam RT | 6.6 (5.7,7.5) | 38.4 (37.3,39.7) | 55.0 (54.0,55.9) | ||
| Poor | Active surveillance | 2.6 (2.2,3.0) | 10.1 (9.6,10.8) | 87.2 (86.4,87.9) | |
| Brachytherapy | 1.3 (0.8,1.7) | 20.3 (19.5,21.1) | 78.5 (77.5,79.5) | ||
| Radical Prostatectomy | 1.0 (0.9,1.1) | 4.3 (3.9,4.8) | 94.7 (94.1,95.2) | ||
| External beam RT | 1.2 (0.9,1.5) | 13.8 (13.0,14.7) | 85.0 (84.2,85.9) | ||
| Urinary Obstruction and Irritation | |||||
| 24 Month Functional Level | |||||
| Normal % (95% CI) | Intermediate % (95% CI) | Poor % (95% CI) | |||
| Baseline Functional Level | Normal | Active surveillance | 42.0 (41.1,42.8) | 44.8 (43.8,45.7) | 13.2 (12.4,14.1) |
| Brachytherapy | 19.3 (17.8,20.9) | 56.9 (54.8,58.6) | 23.9 (22.4,25.3) | ||
| Radical Prostatectomy | 52.7 (52.3,53.2) | 39.1 (38.6,39.6) | 8.1 (7.7,8.6) | ||
| External beam RT | 48.8 (48.0,49.5) | 35.8 (34.8,36.7) | 15.4 (14.5,16.4) | ||
| Intermediate | Active surveillance | 17.0 (16.4,17.6) | 43.6 (42.7,44.5) | 39.4 (38.6,40.2) | |
| Brachytherapy | 18.3 (17.0,19.5) | 44.1 (42.1,46.1) | 37.6 (36.2,39.0) | ||
| Radical Prostatectomy | 30.9 (29.4,32.3) | 54.1 (52.5,55.9) | 15.0 (14.2,15.9) | ||
| External beam RT | 27.6 (26.7,28.6) | 44.6 (43.6,45.5) | 27.8 (26.8,28.7) | ||
| Poor | Active surveillance | 6.3 (5.6,7.0) | 37.0 (36.1,38.0) | 56.7 (55.8,57.7) | |
| Brachytherapy | 14.5 (13.6,15.4) | 33.9 (32.1,35.9) | 51.5 (50.3,52.8) | ||
| Radical Prostatectomy | 24.1 (23.3,24.8) | 51.6 (50.8,52.4) | 24.4 (23.8,24.9) | ||
| External beam RT | 9.2 (8.5,9.9) | 36.7 (35.8,37.7) | 54.1 (53.2,54.8) | ||
| Urinary Incontinence | |||||
| 24 Month Functional Level | |||||
| Normal % (95% CI) | Intermediate % (95% CI) | Poor % (95% CI) | |||
| Baseline Level | Normal | Active surveillance | 72.7 (71.8,73.5) | 20.3 (19.6,21.0) | 7.0 (6.7,7.4) |
| Brachytherapy | 64.8 (63.7,65.8) | 26.2 (25.2,27.2) | 9.0 (8.3,9.7) | ||
| Radical Prostatectomy | 34.3 (33.7,34.8) | 49.9 (49.2,50.6) | 15.8 (15.4,16.3) | ||
| External beam RT | 73.0 (72.3,73.7) | 19.9 (19.3,20.5) | 7.1 (6.6,7.4) | ||
| Intermediate | Active surveillance | 22.5 (21.1,23.7) | 51.4 (49.4,53.4) | 26.1 (24.6,27.6) | |
| Brachytherapy | 38.1 (34.7,41.7) | 32.0 (27.4,36.6) | 29.9 (26.7,33.4) | ||
| Radical Prostatectomy | 15.4 (14.5,16.2) | 67.4 (66.4,68.3) | 17.3 (16.6,17.8) | ||
| External beam RT | 32.2 (31.0,33.6) | 52.1 (51.0,53.3) | 15.7 (14.8,16.6) | ||
| Bowel Problems | |||||
| 24 Month Functional Level | |||||
| Normal % (95% CI) | Intermediate % (95% CI) | Poor % (95% CI) | |||
| Baseline Level | Normal | Active surveillance | 57.2 (56.2,58.2) | 33.5 (32.3,34.8) | 9.3 (8.7,9.9) |
| Brachytherapy | 46.8 (45.1,48.4) | 44.4 (42.7,46.4) | 8.9 (7.6,10.5) | ||
| Radical Prostatectomy | 57.4 (56.3,58.2) | 37.0 (36.1,38.0) | 5.6 (5.2,6.0) | ||
| External beam RT | 42.7 (41.8,43.5) | 39.9 (39.2,40.5) | 17.4 (16.7,18.2) | ||
| Intermediate | Active surveillance | 28.9 (28.1,29.5) | 54.8 (54.1,55.6) | 16.3 (15.5,17.1) | |
| Brachytherapy | 27.0 (26.1,27.8) | 56.9 (56.1,57.7) | 16.2 (15.7,16.7) | ||
| Radical Prostatectomy | 34.8 (34.4,35.2) | 50.5 (50.1,50.9) | 14.7 (14.3,15.1) | ||
| External beam RT | 19.9 (19.0,21.1) | 60.3 (59.1,61.5) | 19.8 (19.1,20.4) | ||
Abbreviations: RT, radiotherapy; CI, confidence interval.
Missing data were imputed.
Normal function describes a patient with essentially no dysfunction or distress in a domain. Intermediate function describes a patient with at least one distressful symptom but none very distressful. Poor function describes patients with at least one very distressful symptom.
Among active surveillance patients, 18.7% received treatment within 24 months: 6.2% radical prostatectomy, 6.9% external beam RT, 3.1% brachytherapy, and 2.4% other.
Urinary obstruction and irritation:
At baseline, propensity-weighted scores were 22.8 (active surveillance, 95% CI 21.2-24.3), 22.3 (RT, 95% CI 20.3-24.4), 20.8 (brachytherapy, 95% CI, 18.3-23.3), and 22.6 (prostatectomy, 95% CI 21.1-24.2)(Table 2). Compared to active surveillance, urinary obstruction and irritation scores increased after brachytherapy at 3 and 12 months but not 24 months (3 months: +20.5, 95% CI 15.1-25.9; 12 months: +5.5, 95% CI 0.4-10.6), and increased after RT at 3 months (+11.7, 95% CI 8.7-14.8). Prostatectomy patients reported lower urinary obstruction and irritation compared to active surveillance at 12 and 24 months (12 months: −4.3, 95% CI −6.9 to −1.7; 24 months: −5.7, 95% CI −8.2 to −3.1). Score differences between brachytherapy and RT vs. active surveillance met threshold for clinical significance at 3-months.
Table 3 details 24 month outcomes in men with different baseline urinary obstruction and irritation levels. For men at normal baseline level, 52.7% (N=36.9/70.0) remained at normal 24 months after prostatectomy, 48.8% (N=37.8/77.5) after RT and only 19.3% (N=17.3/89.6) after brachytherapy. For men who started with intermediate baseline urinary obstruction and irritation, 18.3-30.9% improved after surgical or radiation treatments to normal levels, while 15.0-37.6% worsened to poor. Most men (75.7%, 85.0/112.3) who had poor baseline urinary obstruction and irritation improved after prostatectomy by 2 years; 45.9% of RT (N=48.1/104.8), 48.5% brachytherapy (N=44.7/92.2), and 43.3% (N=45.5/105.1) of active surveillance patients improved.
Urinary incontinence:
At baseline, propensity-weighted scores were 10.4 (active surveillance, 95% CI 8.2-12.8), 9.9 (RT, 95% CI 7.5-12.4), 10.5 (brachytherapy, 95% CI, 3.8-17.2), and 9.7 (prostatectomy, 95% CI 7.2-12.2)(Table 2). Incontinence scores were not significantly different between RT or brachytherapy versus active surveillance at 3, 12, and 24 months. For radical prostatectomy versus active surveillance, incontinence scores increased by 33.6 (3 months, 95% CI 27.8-39.2), 18.2 (12 months, 95% CI 12.9-23.5), and 15.4 (24 months, 95% CI 8.9-21.9); all of these differences were clinically significant.
For men with normal urinary control at baseline, 34.3% (N=74.5/217.2) reported normal control 24 months after prostatectomy, while 15.8% (N=34.4/217.7) reported poor control (Table 3). In other groups, proportions of patients who maintained normal urinary control were 73.0% RT (N=167.2/229.0), 64.8% brachytherapy (N=143.4/221.3), and 72.7% active surveillance (N=164.3/226.0). For men with intermediate urinary control at baseline, 15.7-29.9% reported poor control at 24 months across the groups. Too few patients had baseline poor urinary control (N=50 total) for meaningful analysis of that subgroup.
Bowel Problems:
At baseline, propensity-weighted scores were 5.9 (active surveillance, 95% CI 5.0-6.8), 5.7 (RT, 95% CI 4.6-6.7), 6.1 (brachytherapy, 95% CI 4.5-7.6), and 6.2 (prostatectomy, 95% CI 5.2-7.3)(Table 2). Compared with active surveillance, RT increased scores at 3 months (+4.9, 95% CI 2.4-7.4) and 24 months (+3.7, 95% CI 1.0-6.4). At 3 months, this difference was clinically meaningful. Scores between brachytherapy and prostatectomy vs. active surveillance were not significantly different at any time point.
After RT, 42.7% (N=56.7/132.8) of men who reported normal baseline level also reported normal level at 24 months (Table 3). Corresponding proportions were 46.8% after brachytherapy (N=50.2/107.3), 57.4% prostatectomy (N=70.7/123.2) and 57.2% active surveillance (N=76.7/134.1). In addition, 17.4% (N=23.1/132.8) of RT patients who started at a normal level worsened to poor at 24 months, while 5.6-9.3% of patients in other groups worsened to poor. Too few patients were at baseline poor level for meaningful analysis of that subgroup.
Discussion
Prostate cancer patients have multiple treatment options and face a confusing decision-making process. Therefore, the comparative effectiveness of contemporary treatment options for localized prostate cancer is a top research priority according to the Institute of Medicine.1 While contemporary treatments (robotic surgery, intensity-modulated radiotherapy) were developed to reduce treatment-related morbidity, the comparative effectiveness of these treatments vs. active surveillance is unknown. A population-based cohort can be used to inform this question by providing timely data from patients who are representative of men with prostate cancer. This study addresses one aspect of this comparative effectiveness question by showing that contemporary treatment options were associated with distinct patterns of QOL changes. These data may help inform men in their treatment decision-making process, and also inform the continued debate regarding prostate cancer screening. The US Preventive Services Task Force, in the current process of revising its screening recommendations, specifically indicated a need to review the harms of different treatment approaches.21 This study directly addresses this knowledge gap.
In light of recently published data from the ProtecT trial,4 this study provides new information. This is because the ProtecT trial started in 1999 and used older treatments (3D radiotherapy, non-robotic prostatectomy) which may have limited relevance to informing contemporary patients regarding current treatment options which consist of intensity-modulated radiotherapy,2 robotic prostatectomy,22 and brachytherapy.23 The current study provides QOL outcomes of treatments representative of contemporary choices for patients; the surgical and radiotherapy treatments received by patients in this study (86.6% robotic prostatectomy, 94.8% intensity-modulated radiotherapy) are reflective of treatment patterns in the US.2,22 With advances in both surgical and radiotherapy technologies, the relative QOL results across treatment groups remain similar as those reported by the ProtecT trial: radical prostatectomy was associated with sexual dysfunction and urinary incontinence, while radiotherapy was associated with short-term urinary obstruction and irritation, and bowel symptoms.
Active surveillance is an emerging option for men with early prostate cancers,5 and served as a natural control group for this study, to help inform the decision for men considering this option vs. immediate treatment. This study showed that mean QOL scores for this group remained at baseline levels, until 12 months and after when urinary incontinence and sexual dysfunction scores noticeably increased. This coincides with the timing of guideline-recommended repeat prostate biopsies on active surveillance, with each biopsy expected to detect a proportion of patients with cancer progression necessitating treatment. While surveillance is the most conservative option, it is notable that mean QOL scores at 24 months were not clinically meaningfully different between this group and active treatment groups in most domains. This observation can be explained by the gradual progression of men on surveillance to treatment over time, while men who received immediate treatment experienced gradual improvement in treatment-related symptoms. These findings are consistent with those from the ProtecT trial,24 and provide information that can be used to help counsel patients – and demonstrates that, on average, active surveillance may be associated with preserved QOL, at least in the first 2 years after diagnosis.
While QOL research conventionally reports results using mean scores, it is well recognized that score changes are difficult to interpret by patients and physicians.10,12 Several approaches have been proposed to address this interpretability challenge, including definition of a “minimal clinically important difference” (MCID) or using an arbitrary 0.5-standard deviation change to denote clinically-meaningful change.17,18 A limitation of the PCSI is that it does not have a defined MCID through an anchor-based method, and therefore we took the latter approach in this study. It is also well-established that men with different levels of baseline urinary, bowel, and sexual function likely have different experiences after treatment.9 For example, men with no useful erectile function at baseline are unlikely to experience any meaningful positive or negative effect of their sexual function from treatment; therefore, including these men in overall mean score calculations blunts the observed effect (score changes) experienced by other men who have normal baseline function. The PCSI is unique among existing prostate cancer QOL instruments in having defined functional levels, which provides a framework for defining clinically-meaningful change and also allows stratification of patients by baseline function. Thus, an additional analysis was performed using QOL levels established by the PCSI instrument to complement the reported mean scores.
Physicians can use these data to provide more individualized counseling of their patients regarding expected outcomes of patients with similar levels of baseline function. For example, among men with normal sexual function at baseline, 57.1% were estimated to have poor function at 24 months after prostatectomy; 9% of patients reported preserved normal function, while the other one-third experienced declined but still useful sexual function. Men who chose active surveillance had the largest proportion (44.6%) with preserved normal sexual function at 24 months.
These data also revealed that some QOL aspects can improve after treatment. Older men commonly have benign prostatic hypertrophy with associated urinary obstructive symptoms, which can be improved by prostate cancer treatments. In the group of men who had an intermediate-level of baseline urinary obstruction and irritation symptoms, prostatectomy improved symptoms by 24 months in more patients (30.9%) than worsened (15.0%), and RT improved and worsened similar proportions. These findings are consistent with prior studies.25,26 There are additional possible reasons for some patients experiencing improvements in urinary symptoms – including medical management of symptoms, and surgical and radiation treatments alleviating symptoms caused by the prostate cancer itself.
There are several strengths of this study. Study design was informed by collaboration with a broad group of stakeholders,20 with the goal that this study will provide information relevant to patients and clinicians. This study compared the 4 treatment options most relevant to contemporary patients. However, randomized data suggest that short-term QOL between open versus robotic prostatectomy are not significantly different.27 Population-based design facilitated a sociodemographically diverse cohort including patients who chose active surveillance, and not just patients treated at large academic centers. Another strength is that 100% of patients reported pre-treatment QOL without recall, which allows accurate calculations of treatment effect. The study also utilized a consistent methodology for QOL assessment using telephone survey7 and time points based on treatment date, with measurements which captured both short-term (3 month) and longer-term changes.
There are several limitations of this study. As an observational study which is descriptive in nature, there were imbalances in baseline patient characteristics. Propensity weighting was used to minimize these imbalances across groups, but residual confounding is possible and there remained unbalanced disease characteristics across groups with favorable characteristics for active surveillance patients and relatively less favorable for RT. Patients were not blinded to treatment received, and patient expectations regarding outcomes from the treatment they received could affect their reporting of QOL. Enrollment in the study was only 57%, which could have led to a selection bias, although this was not out of the range of other studies.28 There was missing data especially with longer follow-up (19-29% at 24 month time point), with differential response rates across groups. Further, while participants were recruited from one state, they are broadly representative of men with prostate cancer: the median age of NC ProCESS participants (66) is similar to prostate cancer patients across the US,29 and the types of radiation (94.8% IMRT) and surgical treatments (86.6% robotic) received are similar to US patterns of care studies.2,22 Also, the rapid case ascertainment system of North Carolina uniquely facilitated all participants to be enrolled prior to treatment. This study assessed sexual, urinary and bowel symptoms, which are most commonly affected after prostate cancer treatments, but did not assess general quality of life. In addition, QOL may continue to change more than 2 years after treatment. This analysis included results only through 2 years of follow-up, and further follow-up is ongoing. However, as the ProtecT trial showed,4 there may be little change in QOL after 2 years.
Conclusions:
In this cohort of men with localized prostate cancer, each treatment strategy was associated with distinct patterns of adverse effects over 2 years. These findings may promote treatment decisions that incorporate individual preferences.
Supplementary Material
Key Points
Question:
What differences in quality of life are associated with radical prostatectomy, external beam radiotherapy, brachytherapy, and active surveillance after treatment for prostate cancer?
Findings:
In this population-based, prospective cohort of 1141 men diagnosed from 2011-2013, radical prostatectomy was associated with worse sexual dysfunction and urinary incontinence compared to active surveillance; external beam radiotherapy and brachytherapy worse short-term urinary obstruction and irritation, and external beam radiotherapy worse short-term bowel symptoms. However, by 24 months, mean scores between treatment groups vs. active surveillance were not significantly different in most domains.
Meaning:
Contemporary treatment strategies were associated with distinct patterns of adverse effects over 2 years.
Acknowledgements
Funding/Support: Research reported in this publication was funded through a Patient-Centered Outcomes Research Institute (PCORI) Award (CER-1310-06453) and a contract from Agency for Healthcare Research and Quality.
Work on this study was supported by the Integrated Cancer Information and Surveillance System, UNC Lineberger Comprehensive Cancer Center, with funding provided by the University Cancer Research Fund via the state of North Carolina.
Footnotes
Conflict of Interest: None
Financial Disclosures: We have no disclosures to report and no conflicts of interest.
Role of the Sponsor: The sponsor was not involved with the collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Publisher's Disclaimer: Disclaimer: The statements presented in this publication are solely the responsibility of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute (PCORI), its Board of Governors or Methodology Committee.
Additional Contributions: None.
Prior Presentation: None.
References
- 1.Institute of Medicine. Initial national priorities for comparative effectiveness research. 2009. National Academies Press; Washington, DC. [Google Scholar]
- 2.Sheets NC, Goldin GH, Meyer AM, et al. Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer. JAMA. April 2012;307(15):1611–1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Lowrance WT, Eastham JA, Savage C, et al. Contemporary open and robotic radical prostatectomy practice patterns among urologists in the United States. J Urol. June 2012;187(6):2087–2092. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Donovan JL, Hamdy FC, Lane JA, et al. Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. October 2016;375(15):1425–1437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Chen RC, Rumble RB, Loblaw DA, et al. Active Surveillance for the Management of Localized Prostate Cancer (Cancer Care Ontario Guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement. J Clin Oncol. June 2016;34(18):2182–2190. [DOI] [PubMed] [Google Scholar]
- 6.Clark JA, Talcott JA. Symptom indexes to assess outcomes of treatment for early prostate cancer. Medical care. October 2001;39(10):1118–1130. [DOI] [PubMed] [Google Scholar]
- 7.Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. The New England journal of medicine. March 20 2008;358(12):1250–1261. [DOI] [PubMed] [Google Scholar]
- 8.Martin NE, Massey L, Stowell C, et al. Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer. Eur Urol. September 2014. [DOI] [PubMed] [Google Scholar]
- 9.Chen RC, Clark JA, Talcott JA. Individualizing quality-of-life outcomes reporting: how localized prostate cancer treatments affect patients with different levels of baseline urinary, bowel, and sexual function. J Clin Oncol. August 20 2009;27(24):3916–3922. [DOI] [PubMed] [Google Scholar]
- 10.Chen RC, Chang P, Vetter RJ, et al. Recommended patient-reported core set of symptoms to measure in prostate cancer treatment trials. J Natl Cancer Inst. July 2014;106(7). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Mushlin AI, Ghomrawi H. Health care reform and the need for comparative-effectiveness research. N Engl J Med. January 2010;362(3):e6. [DOI] [PubMed] [Google Scholar]
- 12.Talcott JA, Clark JA, Manola J, Mitchell SP. Bringing prostate cancer quality of life research back to the bedside: translating numbers into a format that patients can understand. The Journal of urology. October 2006;176(4 Pt 1):1558–1563; discussion 1563–1554. [DOI] [PubMed] [Google Scholar]
- 13.Stürmer T, Wyss R, Glynn RJ, Brookhart MA. Propensity scores for confounder adjustment when assessing the effects of medical interventions using nonexperimental study designs. J Intern Med. June 2014;275(6):570–580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. December 2015;34(28):3661–3679. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.van Buuren S Multiple imputation of discrete and continuous data by fully conditional specification. Stat Methods Med Res. June 2007;16(3):219–242. [DOI] [PubMed] [Google Scholar]
- 16.White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance for practice. Stat Med. February 2011;30(4):377–399. [DOI] [PubMed] [Google Scholar]
- 17.Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. May 2003;41(5):582–592. [DOI] [PubMed] [Google Scholar]
- 18.Norman GR, Sloan JA, Wyrwich KW. The truly remarkable universality of half a standard deviation: confirmation through another look. Expert Rev Pharmacoecon Outcomes Res. October 2004;4(5):581–585. [DOI] [PubMed] [Google Scholar]
- 19.Wright JG. Interpreting health-related quality of life scores: the simple rule of seven may not be so simple. Med Care. May 2003;41(5):597–598. [DOI] [PubMed] [Google Scholar]
- 20.Chen RC, Carpenter WR, Kim M, et al. Design of the North Carolina Prostate Cancer Comparative Effectiveness and Survivorship Study (NC ProCESS). Journal of comparative effectiveness research. January 2015;4(1):3–9. [DOI] [PubMed] [Google Scholar]
- 21.US Preventive Services Task Force. Final research plan for prostate cancer: screening. 2016; http://www.uspreventiveservicestaskforce.org/Page/Document/final-research-plan/prostate-cancer-screening1. Accessed September 1, 2016.
- 22.Oberlin DT, Flum AS, Lai JD, Meeks JJ. The effect of minimally invasive prostatectomy on practice patterns of American urologists. Urol Oncol. June 2016;34(6):255.e251–255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Safdieh J, Wong A, Weiner JP, Schwartz D, Schreiber D. Utilization of prostate brachytherapy for low risk prostate cancer: Is the decline overstated? J Contemp Brachytherapy. August 2016;8(4):289–293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Wilt TJ. The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer. J Natl Cancer Inst Monogr. December 2012;2012(45):184–190. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Steineck G, Helgesen F, Adolfsson J, et al. Quality of life after radical prostatectomy or watchful waiting. N Engl J Med. September 2002;347(11):790–796. [DOI] [PubMed] [Google Scholar]
- 26.Chang P, Regan MM, Ferrer M, et al. Relief of Urinary Symptom Burden after Primary Prostate Cancer Treatment. J Urol. February 2017;197(2):376–384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Yaxley JW, Coughlin GD, Chambers SK, et al. Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: early outcomes from a randomised controlled phase 3 study. Lancet. September 2016;388(10049):1057–1066. [DOI] [PubMed] [Google Scholar]
- 28.Potosky AL, Harlan LC, Stanford JL, et al. Prostate cancer practice patterns and quality of life: the Prostate Cancer Outcomes Study. Journal of the National Cancer Institute. October 20 1999;91(20):1719–1724. [DOI] [PubMed] [Google Scholar]
- 29.Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. July 2016;66(4):271–289. [DOI] [PubMed] [Google Scholar]
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