Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer.

To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC). We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios (HRs). The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM (HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3 months; 3-8.9 months; 9-14. months; and ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3 months was associated with an approximately ninefold increased risk of metastases (HR 8.63, 95% CI 5.07-14.7) and PCSM (HR 9.29, 95% CI 5.38-16.0), and a 4.7-fold increased risk of ACM (HR 4.71, 95% CI 2.98-7.43) on multivariable analysis compared with PSADT ≥15 months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ≥15 months were 9, 19, 40 and 50 months, respectively. Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ≥15 months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials.

Howard LE ，Moreira DM ，De Hoedt A ，Aronson WJ ，Kane CJ ，Amling CL ，Cooperberg MR ，Terris MK ，Freedland SJ ... -  《-》

Impact of age, comorbidity, and PSA doubling time on long-term competing risks for mortality among men with non-metastatic castration-resistant prostate cancer.

Whitney CA ，Howard LE ，Freedland SJ ，DeHoedt AM ，Amling CL ，Aronson WJ ，Cooperberg MR ，Kane CJ ，Terris MK ，Daskivich TJ ... -  《-》

Positive surgical margins in radical prostatectomy patients do not predict long-term oncological outcomes: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.

To assess the impact of positive surgical margins (PSMs) on long-term outcomes after radical prostatectomy (RP), including metastasis, castrate-resistant prostate cancer (CRPC), and prostate cancer-specific mortality (PCSM). Retrospective study of 4,051 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort treated by RP from 1988 to 2013. Proportional hazard models were used to estimate hazard ratios (HRs) of PSMs in predicting biochemical recurrence (BCR), CRPC, metastases, and PCSM. To determine if PSMs were more predictive in certain patients, analyses were stratified by pathological Gleason score, stage, and preoperative prostate-specific antigen (PSA) level. The median (interquartile range) follow-up was 6.6 (3.2-10.6) years and 1 127 patients had >10 years of follow-up. During this time, 302 (32%) men had BCR, 112 (3%) developed CRPC, 144 (4%) developed metastases, and 83 (2%) died from prostate cancer. There were 1,600 (40%) men with PSMs. In unadjusted models, PSMs were significantly associated with all adverse outcomes: BCR, CRPC, metastases and PCSM (all P ≤ 0.001). After adjusting for demographic and pathological characteristics, PSMs were associated with increased risk of only BCR (HR 1.98, P < 0.001), and not CRPC, metastases, or PCSM (HR ≤1.29, P > 0.18). Similar results were seen when stratified by pathological Gleason score, stage, or PSA level, and when patients who underwent adjuvant radiotherapy were excluded. PSMs after RP are not an independent risk factor for CRPC, metastasis, or PCSM overall or within any subset. In the absence of other high-risk features, PSMs alone may not be an indication for adjuvant radiotherapy.

Mithal P ，Howard LE ，Aronson WJ ，Terris MK ，Cooperberg MR ，Kane CJ ，Amling C ，Freedland SJ ... -  《-》

Does Early Prostate Specific Antigen Doubling Time after Radical Prostatectomy, Calculated Prior to Prostate Specific Antigen Recurrence, Correlate with Prostate Cancer Outcomes? A Report from the SEARCH Database Group.

Short prostate specific antigen doubling time following recurrence after radical prostatectomy portends a poor prognosis. Prostate specific antigen doubling time is traditionally calculated using prostate specific antigen values 0.2 ng/ml or greater. We determined whether early prostate specific antigen doubling time, calculated from the first detectable postoperative prostate specific antigen up to and including the first recurrence value, correlates with prostate cancer outcomes. Cox models were used to examine the association between early prostate specific antigen doubling time and castration resistant prostate cancer, metastases, and all cause and prostate cancer specific mortality in 674 men who underwent radical prostatectomy between 1988 and 2014 and had a biochemical recurrence. Early prostate specific antigen doubling time was examined as a log transformed continuous and a categorical variable. After adjusting for multiple clinicopathological characteristics, log transformed early prostate specific antigen doubling time was not associated with any outcome. However, when early doubling time was categorized as 15 or greater, 9 to 14.9, 3 to 8.9 and less than 3 months, on multivariable analysis men with early doubling time less than 3 months were at increased risk for castration resistant prostate cancer (HR 6.20, p = 0.004), metastases (HR 5.26, p = 0.001), prostate cancer specific mortality (HR 5.06, p = 0.026) and all cause mortality (HR 1.63, p = 0.065) compared to those with an early doubling time of 15 months or greater. However, the association with all cause mortality was not significant. Those with an early prostate specific antigen doubling time of 3 to 8.9 months were at increased risk for castration resistant prostate cancer (HR 3.56, p = 0.015), all cause mortality (HR 1.67, p = 0.006) and prostate cancer specific mortality (HR 3.17, p = 0.044) but not metastases (p = 0.13). Early prostate specific antigen doubling time less than 9 months, calculated using prostate specific antigen values before and up to biochemical recurrence, is associated with an increased risk of castration resistant prostate cancer, metastases, and prostate cancer specific and all cause mortality among men with biochemical recurrence after radical prostatectomy. Early prostate specific antigen doubling time allows for risk stratification at biochemical recurrence and before prostate specific antigen doubling time is calculable, enabling these men to be referred for early aggressive secondary treatment and/or clinical trials.

Teeter AE ，Griffin K ，Howard LE ，Aronson WJ ，Terris MK ，Kane CJ ，Amling CL ，Cooperberg MR ，Freedland SJ ... -  《-》

A prostate-specific antigen doubling time of <6 months is prognostic for metastasis and prostate cancer-specific death for patients receiving salvage radiation therapy post radical prostatectomy.

Jackson WC ，Johnson SB ，Li D ，Foster C ，Foster B ，Song Y ，Schipper M ，Shilkrut M ，Sandler HM ，Morgan TM ，Palapattu GS ，Hamstra DA ，Feng FY ... -  《-》