Stability of Prognostic Estimation Using the CAPRA Score Incorporating Imaging-based vs Physical Exam-based Staging.

PURPOSE: Although official T-staging criteria for prostate cancer are based on digital rectal examination findings, providers increasingly rely on transrectal US and MRI to define pragmatic clinical stage to guide management. We assessed the impact of incorporating imaging findings into T-staging on performance of a well-validated prognostic instrument. MATERIALS AND METHODS: Patients who underwent radical prostatectomy for prostate cancer diagnosed between 2000 and 2019 with stage ≤cT3a on both digital rectal examination and imaging (transrectal US/MRI) were included. The University of California, San Francisco CAPRA (Cancer of the Prostate Risk Assessment) score was computed 2 ways: (1) incorporating digital rectal examination-based T stage and (2) incorporating imaging-based T stage. We assessed for risk changes across the 2 methods and associations of CAPRA (by both methods) with biochemical recurrence, using unadjusted and adjusted Cox proportional hazards models. Model discrimination and net benefit were assessed with time-dependent area under the curve and decision curve analysis, respectively. RESULTS: Of 2,222 men included, 377 (17%) increased in CAPRA score with imaging-based staging (P < .01). Digital rectal examination-based (HR 1.54; 95% CI 1.48-1.61) and imaging-based (HR 1.52; 95% CI 1.46-1.58) CAPRA scores were comparably accurate for predicting recurrence with similar discrimination and decision curve analyses. On multivariable Cox regression, positive digital rectal examination at diagnosis (HR 1.29; 95% CI 1.09-1.53) and imaging-based clinical T3/4 disease (HR 1.72; 95% CI 1.43-2.07) were independently associated with biochemical recurrence. CONCLUSIONS: The CAPRA score remains accurate whether determined using imaging-based staging or digital rectal examination-based staging, with relatively minor discrepancies and similar associations with biochemical recurrence. Staging information from either modality can be used in the CAPRA score calculation and still reliably predict risk of biochemical recurrence.

The Natural History of Untreated Biopsy Grade Group Progression and Delayed Definitive Treatment for Men on Active Surveillance for Early-Stage Prostate Cancer.

PURPOSE: For men with clinically localized prostate cancer outcomes of continuing active surveillance (AS) after biopsy progression are not well understood. We aim to determine the impact of continuing AS and delayed definitive treatment after biopsy progression on oncologic outcomes. MATERIALS AND METHODS: Participants in our prospective AS cohort (1990-2018) diagnosed with grade group (GG) 1, localized prostate cancer, with prostate specific antigen <20 who were subsequently upgraded to ≥GG2, and underwent further surveillance (biopsy/imaging/prostate specific antigen) were identified. Patients were stratified by post-progression followup into 3 groups: continue AS untreated, pursue early radical prostatectomy (RP) ≤6 months, or undergo late RP within 6 months to 5 years of progression. Patients receiving other treatments were excluded. We compared characteristics between groups and examined the associations of early vs late RP with risk of adverse pathology (AP) at RP and recurrence-free survival (RFS) after RP. RESULTS: Of 531 patients with biopsy progression and further surveillance 214 (40%) remained untreated, 192 (36%) pursued early RP and 125 (24%) underwent late RP. Among patients who underwent early vs late RP, there was no difference in GG (p=0.15) or AP (55% vs 53%, p=0.74) rate at RP, or 3-year RFS (80% vs 87%, log-rank p=0.64) after RP. In multivariable models, only Cancer of Prostate Risk Assessment post-surgical score was associated with risk of RFS (HR=1.42 per point, 95% CI 1.24-1.64). CONCLUSIONS: Among patients continuing AS after biopsy progression, 60% underwent surgery within 5 years. Delayed surgery after progression was not associated with higher risk of AP or RFS. This suggests select patients may be able to safely delay treatment after progression.

Natural history of an immediately detectable PSA following radical prostatectomy in a contemporary cohort.

BACKGROUND: A detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) is an unfavorable prognostic factor. However, not all men with a detectable PSA experience recurrence. We describe the natural history and outcomes in men with a detectable PSA following RP in a contemporary cohort. METHODS: A retrospective analysis of men who underwent RP for non-metastatic prostate cancer at the University of California, San Francisco from 2000 to 2020 was performed. A detectable PSA was defined as PSA ≥ 0.03 ng/ml within 6 months of RP. Cox regression models tested the effect of detectable PSA on the development of metastasis, prostate cancer-specific mortality, and overall survival. RESULTS: We identified 2941 men who had RP with 408 (13.9%) with a detectable PSA within the first 6 months. The median follow-up was 4.42 years (interquartile range [IQR], 2.58-8.00). In total, 296 (72.5%) men with a detectable PSA had salvage treatment at a median of 6 months (IQR, 4-11). One hundred sixteen of these men had PSA failure after salvage treatment at a median of 2.0 years (IQR, 0.7-3.8). On multivariable Cox regression, the risk of development of metastasis (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.09; p = .01), prostate cancer-specific mortality (HR, 1.13; 95% CI, 1.05-1.21; p = .0005), and overall mortality (HR, 1.07; 95% CI, 1.03-1.12; p = .002) was associated with PSA velocity after salvage treatment in men with a detectable PSA. CONCLUSIONS: Men with a detectable PSA after RP may have excellent long-term outcomes. PSA velocity after salvage treatment may be an important predictor for the development of metastasis, prostate cancer-specific mortality, and overall mortality.

Residual Benign Prostate Glandular Tissue after Radical Prostatectomy is Not Associated with the Development of Detectable Postoperative Serum Prostate Specific Antigen.

PURPOSE: To determine if benign glandular tissue at the surgical margin (BGM) is associated with detectable prostate specific antigen (PSA) and/or biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: Participants underwent RP for localized prostate cancer between 2004 and 2018. Regression analysis was used to identify demographic, clinical and surgical factors associated with the likelihood of BGM presence on surgical pathology. Oncologic outcomes included detectable PSA (>0.03 ng/ml), BCR (≥0.2 ng/ml) and progression to BCR or salvage treatment after detectable PSA. Life tables and Cox proportional hazards regression models were used to determine the association of BGM and risk of oncologic outcomes. RESULTS: A total of 1,082 men underwent RP for localized prostate cancer with BGM reported on surgical pathology and an undetectable postoperative PSA. BGM was present on 249 (23%) specimens. Younger age, bilateral nerve sparing surgery and robotic approach were associated with presence of BGM while malignancy at the surgical margin (MSM) was not. At 7 years after RP, 29% experienced detectable PSA and 11% had BCR. In the subgroup of men who reached detectable PSA, 79% had progression within 7 years. On multivariate Cox proportional hazards regression, BGM status was not independently associated with detectable PSA, BCR and/or progression from detectable PSA to BCR or salvage treatment. CONCLUSIONS: The presence of BGM at RP was not associated with increased risk of MSM, detectable PSA, BCR or progression after detectable PSA.

The Long-term Incidence and Quality of Life Outcomes Associated With Treatment-Related Toxicities of External Beam Radiotherapy for Prostate Cancer.

OBJECTIVE: To assess the long-term incidence of treatment-related toxicities and quality of life (QOL) outcomes associated with toxicity after external beam radiotherapy (EBRT) for prostate cancer. METHODS: We identified all men who had EBRT between 1994 and 2017 from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a longitudinal, nationwide prostate cancer registry. CaPSURE was queried for patient-reported and International Classification of Diseases-9/10 and Current Procedural Terminology codes. The Medical Outcomes Studies Short Form 36 and the University of California, Los Angeles Prostate Cancer Index were used to provide measures of general health, sexual, urinary, and bowel function. Repeated measures mixed models were used to determine QOL change after onset of toxicity. RESULTS: From a total of 15,332, 1744 (11.4%) men had EBRT. The median follow-up was 7.9years (interquartile range [IQR] 4.3-12.7). The median time to onset of any toxicity including urinary pad usage in 265 (15.4% at 8years) men was 4.3years (IQR 1.8-8.0). The most frequent toxicity was hemorrhagic cystitis (104, 5.9% at 8years) after a median of 3.7years (1.3-7.8), gastrointestinal (48, 2.7% at 8years) after a median of 4.2years (IQR 1.3-7.8), followed by urethral stricture (47, 2.4% at 8years) after a median of 3.7years (IQR 1.9-9.1). Repeated measures mixed models found that onset of hemorrhagic cystitis was associated with change in general health over time. CONCLUSION: EBRT for prostate cancer is associated with distinct treatment-related toxicities which can occur many years after treatment and can affect QOL. These results may help men understand the long-term implications of treatment decisions.

The effect of preoperative membranous urethral length on likelihood of postoperative urinary incontinence after robot-assisted radical prostatectomy.

BACKGROUND: Urinary incontinence after radical prostatectomy affects many men. In addition to surgical and patient factors, longer preoperative membranous urethral length (MUL) has been suggested to be associated with improved postoperative urinary continence outcomes. Here, we assess the association of preoperative MUL and the risk of persistent postoperative urinary incontinence after robot-assisted radical prostatectomy (RARP) for prostate cancer on extended follow-up. METHODS: All participants underwent RARP at the University of California, San Francisco between 2000-2018. Patients were excluded if preoperative MRI-measured MUL was not performed by a radiologist. A single, blinded urologist remeasured MUL retrospectively. Logistic regression models examined associations between radiologist- and urologist-measured MUL and likelihood of persistent incontinence post-RARP by two definitions: strict incontinence (>0 pad/day) and social incontinence (>1 pad/day). RESULTS: In 251 men with a median follow-up of 42 months (IQR 29-76), the median MUL measurements were 14 mm ([IQR 12-17], radiologist) and 15 mm ([IQR 12-18], urologist) with poor agreement (interclass correlation coefficient 0.34). On logistic regression, urologist-measured longer MUL was associated with lower likelihood of strict incontinence within 6 months (odds ratio [OR] 0.87; 95% confidence interval [CI] 0.81-0.94) and 12 months (OR 0.90; 95% CI 0.82-0.98) and social incontinence within 6 months (OR 0.93; 95% CI 0.86-1.00) and 12 months (OR 0.84; 95% CI 0.74-0.95). Radiologist-measured longer MUL was associated with lower likelihood of strict incontinence within 6 months (OR 0.93; 95% CI 0.87-1.00) and social within 12 months (OR 0.87; 95% CI 0.77-1.00). MUL was not associated with likelihood of strict or social incontinence within 24 months. CONCLUSION: Preoperative MRI-measured MUL was not associated with urinary incontinence after 12 months post-RARP. Poor agreement between radiologists' and urologist's measurements supports standardizing MUL measurements to establish the likelihood of early incontinence.