scholarly journals Adjuvant Versus Early Salvage Radiation Therapy for Men at High Risk for Recurrence Following Radical Prostatectomy for Prostate Cancer and the Risk of Death

2021 ◽  
pp. JCO.20.03714
Author(s):  
Derya Tilki ◽  
Ming-Hui Chen ◽  
Jing Wu ◽  
Hartwig Huland ◽  
Markus Graefen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Radical Prostatectomy ◽  
Causal Effect ◽  
Specific Antigen ◽  
Study Cohort ◽  
Adjuvant Radiation ◽  
Salvage Radiation Therapy ◽  
Risk Of Death ◽  
The Impact

PURPOSE Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility. METHODS We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy. RESULTS After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 [0.13-0.85]; P = .02) or included (0.66 [0.44-0.99]; P = .04). CONCLUSION Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists.

Advancing age and the risk of adverse pathology at radical prostatectomy in men with biopsy Gleason score 6 prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 289-289
Author(s):  
Daniel Kim ◽  
Ming-Hui Chen ◽  
Hartwig Huland ◽  
Markus Graefen ◽  
Derya Tilki ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Specific Antigen ◽  
Cancer Center ◽  
Study Cohort ◽  
Pathologic Features ◽  
Younger Men ◽  
Biopsy Gleason Score ◽  
The Impact

289 Background: We evaluated the impact of age > 65 years versus younger on the odds of finding adverse pathologic features (pT3/T4 and/or R1 and/or Gleason score 8, 9, 10) at radical prostatectomy (RP) among men with biopsy Gleason score 6 prostate cancer (PC). Methods: The study cohort comprised 3191 men with biopsy Gleason score 6 PC treated with a RP between February 28, 1992 and February 15, 2016 at the Martini-Klinik Prostate Cancer Center. Multivariable logistic regression was used to evaluate the impact of age > 65 years versus younger on the adjusted odds ratio (AOR) of finding adverse pathology at RP adjusting for pre-RP prostate specific antigen (PSA), clinical tumor category, year of diagnosis, percent positive biopsies (PPB), and PSA density (PSAd). Results: Men age > 65 years as compared to younger had significantly lower median PPB (16.67% vs 20.0%; p = 0.01) and PSAd (0.13 ng/mL vs 0.15 ng/mL; p < 0.0001). Yet, while both increasing PPB (AOR 1.018, 95% CI 1.013, 1.023; p- < 0.0001) and PSAd (AOR 4.28, 95% CI 1.66, 11.01; p = 0.003) were significantly associated with an increased odds of finding adverse pathology at RP, men age > 65 years versus younger had a higher odds of adverse pathology at RP (AOR 1.28, 95% CI 1.002, 1.62; p = 0.048). Conclusions: Despite a more favorable median PPB and PSAd, men with biopsy Gleason score 6 PC and who are age > 65 years compared to younger men are at higher risk for having adverse pathology at RP and may benefit from a multiparametric MRI and targeted biopsy before proceeding with active surveillance. If higher grade/stage disease is discovered and treatment indicated then this information could guide both the use and duration of supplemental androgen deprivation therapy in men considering radiation therapy.

Redefining the role of adjuvant versus salvage radiation therapy for prostate cancer after radical prostatectomy for T3 disease and/or positive margins.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 367-367
Author(s):  
Barry W. Goy ◽  
In-Lu Amy Liu
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Hormonal Therapy ◽  
Salvage Therapy ◽  
Low Risk ◽  
Adjuvant Radiation ◽  
Positive Margins ◽  
Salvage Radiation Therapy

367 Background: SWOG 8794 recommends adjuvant radiation therapy (ART) after radical prostatectomy (RP) for T3 and/or positive margins. Our purpose was to assess 12-year outcomes on 862 RP patients who had either T3 and/or positive margins who underwent surveillance, salvage radiation therapy (SRT), or hormonal therapy (HT), while categorizing these patients into very low risk (VLR), low risk (LR), high risk (HR), and ultra high risk (UHR) groups. Methods: From 2004 - 2007, 862 RP patients had adverse factors of extracapsular penetration (T3a), seminal vesicle invasion (T3b), positive margins, and/or detectable post-operative PSA. Management included surveillance (54.8%), SRT (36.8%), and HT (8.5%) as first salvage therapy, and 21.5% eventually received hormonal therapy. Twenty patients underwent ART, and were excluded from this analysis. We assessed prognostic factors using multivariable analysis, and 12-year estimates of freedom from biochemical failure (FFBF), freedom from salvage therapy (FFST), distant metastases-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS). VLR were those with Gleason Score (GS) of 6. LR were GS 3+4 with only T3a or positive margins, but an undetectable postoperative PSA <0.1. HR were T3b with GS 7-10, any GS 7-10 with T3a/b and positive margins, but an undetectable PSA. UHR were those with a detectable PSA with a GS 7-10. Results: Median follow-up was 12.1 years. Median age was 61.6 years. Median time to first salvage treatment for VLR, LR, HR, and UHR were 10.8, 11.1, 5.3, and 0.6 years, p<0.001. 12-year estimates of FFBF for VLR, LR, HR, and UHR were 60.2%, 52.9%, 28.4%, and 0%, p<0.0001. For FFST, 70.9%, 68.6%, 40.5%, and 0%, p<0.0001. For DMFS, 99.1%, 97.8%, 88.6%, and 63.6%, p<0.0001. For PCSS, 99.4%, 99.5%, 93.5%, and 78.9%, p<0.0001. For OS, 91.8%, 91.8%, 81.0%, and 69.9%, p<0.0001. Conclusions: Outcomes of T3 and/or positive margins using surveillance or SRT as initial management yields excellent outcomes for VLR and LR groups, in which ART should be avoided. For HR, ART can be considered reasonable, since FFBF is only 28.4%. For VHR, these patients may benefit from combined hormonal therapy and ART.

Risk of death from prostate cancer after radical prostatectomy or brachytherapy in men with low- or intermediate-risk disease.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 198-198
Author(s):  
N. D. Arvold ◽  
M. Chen ◽  
J. W. Moul ◽  
B. J. Moran ◽  
D. E. Dosoretz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Specific Antigen ◽  
Low Risk ◽  
Study Cohort ◽  
Intermediate Risk ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference

198 Background: Radical prostatectomy (RP) and brachytherapy (BT) are widely utilized treatments for favorable-risk prostate cancer (PC). We estimated the risk of PC-specific mortality (PCSM) following RP or BT in men with low- or intermediate-risk PC using prospectively collected data. Methods: The study cohort comprised 5,760 men with low-risk PC (prostate-specific antigen [PSA] level ≤ 10 ng/mL, clinical category T1c or 2a, and Gleason score ≤ 6), and 3,079 men with intermediate-risk PC (PSA level 10-20 ng/mL, clinical T2b or T2c, or Gleason score 7). Competing risks multivariable regression was performed to assess risk of PCSM after RP or BT, adjusting for age, treatment year, cardiovascular comorbidity, and known PC prognostic factors. Results: There was no significant difference in the risk of PCSM among men with low-risk PC (11 vs. 6 deaths: adjusted hazard ratio [AHR], 1.62; 95% CI, 0.59–4.45; P = 0.35) who received BT compared to RP. However among men with intermediate-risk PC, despite significantly shorter median follow-up for men undergoing BT as compared to RP (4.1 vs. 7.2 years, P < 0.001), there was a trend toward an increased risk of PCSM (18 vs. 9 deaths: AHR, 2.30; 95% CI, 0.95–5.58; P = 0.07) for men treated with BT. Conclusions: The risk of PCSM among men with low-risk PC was not significantly different following RP or BT, however there may be a reduced risk of PCSM after RP as compared to BT in men with intermediate-risk PC. [Table: see text] No significant financial relationships to disclose.

Gleason pattern 5 as a pathologic predictor of recurrence, development of metastasis, and prostate cancer-specific death for patients receiving salvage radiation therapy following radical prostatectomy.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 151-151
Author(s):  
William C. Jackson ◽  
Skyler B. Johnson ◽  
Corey Foster ◽  
Darren Li ◽  
Benjamin Foster ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Radical Prostatectomy ◽  
Risk Stratification ◽  
Univariate Analysis ◽  
External Beam Radiation ◽  
Adjuvant Radiation ◽  
Beam Radiation ◽  
Gleason Pattern ◽  
The Impact

151 Background: The presence of primary, secondary, and tertiary Gleason pattern 5 (GP5) in prostate cancer has been shown to predict outcomes and improve risk stratification following radical prostatectomy (RP) and external beam radiation therapy (EBRT). However, the predictive value of GP5 has not been assessed in salvage EBRT (SRT) for a rising PSA after RP. We sought to assess the prognostic capability of the presence of GP5 in this setting. Methods: 575 patients who received SRT at a single institution for biochemical recurrence after RP were retrospectively reviewed in an IRB approved analysis. We assessed the impact of GP5 on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) using Kaplan-Meier and Cox Proportional Hazards models. Results: Median follow up was 56.7 months post SRT. On pathologic evaluation, 563 patients had a documented Gleason score (GS). 60 patients (10.7%) had primary, secondary, or tertiary GP5. GP5 was the strongest pathologic predictor of DM (p<0.01 HR: 1.9 [95%CI: 1.3-2.9]) and PCSM (p<0.01 HR: 4.0 [95%CI: 2.1-7.7]) on univariate analysis. The presence of GP5 was a better predictor of BF, DM, PCSM, and OS than stratification by GS8-10. Patients with GP5 had clinically worse outcomes than GS8 patients without GP5. There was no difference in outcome between primary, secondary, and tertiary GP5. On multivariate analysis, GP5 was the strongest pathologic predictor of BF (p<0.01 HR: 2.7 [95%CI: 1.6-4.5]), DM (p<0.01 HR: 11.2 [95%CI: 3.9-32.2]), and PCSM (p<0.01 HR: 6.0 [95%CI: 1.8-19.6]). Conclusions: In SRT, where pathologic factors including extra-capsular extension, seminal vesicle invasion, and margin status are known, the presence of GP5 is the strongest pathologic predictor of BF, DM, and PCSM. Traditional GS risk stratification fails to fully utilize the prognostic capabilities of individual GP’s for SRT patients following RP. Intensification of treatment regimens, such as early use of androgen deprivation therapy or adjuvant radiation, may be appropriate for patients with GP5 in this setting.

A comparison of surrogate endpoints for all cause mortality in men with localized unfavorable-risk prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 21-21
Author(s):  
Trevor Joseph Royce ◽  
Ming-Hui Chen ◽  
Jing Wu ◽  
Marian Loffredo ◽  
Andrew A. Renshaw ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Specific Antigen ◽  
Study Cohort ◽  
Risk Of Death ◽  
Psa Failure ◽  
All Cause Mortality ◽  
Risk Prostate Cancer ◽  
Psa Nadir ◽  
The Impact

21 Background: Several surrogates for prostate cancer-specific mortality exist, but whether these are surrogates for all cause mortality (ACM), and how their performance compares, is unknown. We investigated the relative efficacy of 4 candidate surrogates for ACM using the proportion of treatment effect (PTE) metric. Methods: Two-hundred and six men with localized unfavorable-risk prostate cancer were randomized to radiation therapy (RT) or RT and 6 months of androgen-deprivation therapy (ADT) from 1995 to 2001 and followed for a median of 16.62 years. Among the 159 men with no or minimal comorbidity, a significant reduction in the risk of death was observed in those randomized to RT and ADT versus RT alone; these 159 men formed the study cohort. In order to assess whether the candidate surrogated satisfied Prentice’s criteria for surrogacy, Cox regression analyses were performed to assess the risk of death for each of the candidate surrogates and treatment before and after adjusting for prostate-specific antigen (PSA), age at randomization, T category, and Gleason score. Results: PSA nadir > 0.5 ng/mL, PSA doubling time < 9 months and interval to PSA failure < 30 months met Prentice’s criteria for surrogacy (P = 0.01, 0.003, and 0.03 for the surrogate covariate in the multivariable model, respectively) for ACM, while PSA failure did not (P = 0.10). For the three surrogates, the PTE values were 103.86%, 43.09%, and 41.26%, respectively. Conclusions: A PSA nadir value of > 0.5 ng/mL following RT and ADT identified men prior to PSA failure who were at high-risk for death and therefore could be used to select men for entry, at the time of PSA nadir and before PSA failure, onto randomized trials evaluating the impact on survival of salvage ADT with or without agents shown to prolong survival in men with castrate-resistant metastatic prostate cancer. By enriching study cohorts with men who have achieved a surrogate endpoint for ACM, one can enhance the likelihood that the study will be able to observe whether survival is prolonged when novel treatment is added to ADT, as compared to ADT alone, in an abbreviated time period. Clinical Trial Number: NCT00116220

Predictors of Prostate Cancer–Specific Mortality After Radical Prostatectomy or Radiation Therapy

2005 ◽  
Vol 23 (28) ◽  
pp. 6992-6998 ◽  
Author(s):  
Ping Zhou ◽  
Ming-Hui Chen ◽  
David McLeod ◽  
Peter R. Carroll ◽  
Judd W. Moul ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Specific Antigen ◽  
Study Cohort ◽  
Psa Failure ◽  
Specific Mortality ◽  
Cancer Specific Mortality ◽  
Biopsy Gleason Score

Purpose We evaluated predictors of prostate cancer–specific mortality (PCSM) after prostate-specific antigen (PSA) failure after radical prostatectomy (RP) or radiation therapy (RT). Patients and Methods A total of 1,159 men with clinically localized prostate cancer treated with RP (n = 498) or RT (n = 661) developed PSA failure, and they formed the study cohort. Competing risk regression analyses were used to evaluate whether previously identified predictors of time to metastasis, including post-treatment PSA doubling time (PSA-DT), Gleason score, and interval to PSA failure, could also predict time to PCSM after PSA failure. The cumulative incidence method was used to estimate PCSM after PSA failure. Results A post-RP PSA-DT of less than 3 months (hazard ratio [HR], 54.9; 95% CI, 16.7 to 180), a post-RT PSA-DT of less than 3 months (HR, 12.8; 95% CI, 7.0 to 23.1), and a biopsy Gleason score of 8 to 10 (HR, 6.1; 95% CI, 3.4 to 10.7) for patients treated with RT were significantly associated with PCSM. Post-RP estimated rates of PCSM 5 years after PSA failure were 31% (95% CI, 17% to 45%) v 1% (95% CI, 0% to 2%) for patients with PSA-DT of less than 3 months v ≥ 3 months. Post-RT estimated rates of PCSM 5 years after PSA failure were 75% (95% CI, 59% to 92%) v 35% (95% CI, 24% to 47%) for patients with a biopsy Gleason score of ≥ 8 v ≤ 7, respectively, and PSA-DT of less than 3 months; these rates were 15% (95% CI, 0.8% to 28%) v 4% (95% CI, 1% to 6%), respectively, for patients with a PSA-DT ≥ 3 months. Conclusion Patients at high risk for PCSM after PSA failure can be identified based on post-RP PSA-DT or post-RT PSA-DT and biopsy Gleason score. These parameters may be useful in identifying patients for a randomized trial evaluating hormonal therapy with or without docetaxel.

scholarly journals Prostate-specific antigen is a predictor of the efficacy of salvage radiation therapy in patients with recurrent prostate cancer after radical prostatectomy

2019 ◽  
Vol 15 (2) ◽  
pp. 66-72
Author(s):  
Р. V. Bulychkin ◽  
S. I. Tkachev ◽  
V. B. Matveev ◽  
A. V. Nazarenko
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Radical Prostatectomy ◽  
Prostate Specific Antigen ◽  
Doubling Time ◽  
Specific Antigen ◽  
Salvage Radiotherapy ◽  
Recurrent Prostate Cancer ◽  
Study Objective ◽  
Salvage Radiation Therapy

The study objective is to determine advisability of radiation therapy in patients with recurrent prostate cancer after radical prostatectomy.Materials and methods. In our research 92 patients were treated by salvage radiation therapy after radical prostatectomy. The median of follow up is 48 months.Results. The rates of 1, 2 and 3 years disease-free survival were 96, 91 and 86 %. We received that prostate specific antigen doubling time <6 months and prostate specific antigen >0.5 ng/ml before salvage radiation therapy statistical significance associated with biochemical failure. The results of our study indicate two main negative factors in the prognosis of the efficacy of radiotherapy and combined hormone therapy in patients with biochemical or clinical locoregional recurrence – the period of prostate specific antigen doubling time less than 6 months (p = 0.035) after radical prostatectomy and a higher prostate specific antigen level, especially more than 0.5 ng/ml before salvage radiotherapy (p = 0.037).Conclusion. Taking into account the absence of differences in the results of treatment between groups of patients with clinical and biochemical recurrences, it is not advisable to postpone the implementation of salvage radiotherapy and recommend patients to repeat the study. Repeated studies of these patients, as a rule, are conducted after many months at a higher level of the prostate specific antigen, which is associated with a higher tumor activity and a worse prognosis of the disease.

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