Risk Of Prostate Cancer-specific Mortality In Men Research Articles

Prostate‐specific antigen levels of ≤4 and >4 ng/mL and risk of prostate cancer‐specific mortality in men with biopsy Gleason score 9 to 10 prostate cancer

Defining workup beyond usual clinical practice that may improve treatment outcomes in men with a prostate-specific antigen (PSA) level of ≤4 ng/mL (vs >4 ng/mL) and Gleason score (GS) 9 to 10 prostate cancer (PC) remains to be determined. Between February 25, 1992, and February 25, 2016, 17,632 men with clinical T1-4 PC with a biopsy GS of 6 to 10 underwent radical prostatectomy at a single academic center. Multivariable Fine and Gray regressions were used to evaluate the risk of prostate cancer-specific mortality (PCSM) with an interaction model evaluating the prognostic significance of PSA ≤ 4 ng/mL versus PSA > 4 ng/mL among men with PC with a biopsy GS of 9 to 10 versus ≤8, with adjustments made for the time-dependent use of adjuvant and/or salvage radiation therapy and androgen deprivation therapy (ADT) in addition to known PC prognostic factors. There was a significant interaction in men with a biopsy GS of 9 to 10 versus ≤8 and a PSA level of ≤4 ng/mL versus >4 ng/mL (adjusted hazard ratio [AHR], 2.87; 95% confidence interval [CI], 1.02-8.08; P = .046). Specifically, among men with a biopsy GS of 9 to 10 and a PSA level of ≤4 ng/mL versus >4 ng/mL, there was a significantly higher rate of PCSM (AHR, 2.59; 95% CI, 1.19-5.67; P = .017); however, there was no significant difference in the risk of PCSM in men with a biopsy GS ≤ 8 and a PSA level of ≤4 ng/mL versus >4 ng/mL (AHR, 0.90; 95% CI, 0.46-1.78; P = .771). Moreover, the time-dependent use of postoperative ADT was also associated with an increased risk of PCSM (AHR, 10.76; 95% CI, 6.88-16.81; P < .0001). Some men with PSA ≤ 4 ng/mL and a biopsy GS of 9 to 10 may have pathologic or genetic variants that make them less amenable to a cure with current standards of care. Additional workup assessing for small cell, neuroendocrine, and genetic variants should be considered.

The risk of prostate cancer mortality and cardiovascular mortality of nonmetastatic prostate cancer patients: A population-based retrospective cohort study

PurposeTo assess the risk of prostate cancer (PCa) specific mortality (PCSM) compared to cardiovascular disease mortality (CVDM), or other-cause mortality (OCM) of men with nonmetastatic PCa according to PCa risk groups, primary treatment, and age. Patients and methodsThis retrospective population-based cohort study identified 1,908 nonmetastatic PCa patients in the cancer registry Zurich and Zug, diagnosed between 2000 and 2009 living in the City of Zurich. Multiple imputation methods were applied to handle missing PCa information. Fine and Gray competing risk regression analysis was used to estimate subdistribution hazard ratios for the outcomes PCSM, CVDM, or OCM ResultsTen years after diagnosis the cumulative probability of PCSM and CVDM was 16.4% and 10.0%, respectively. We observed an increased adjusted risk of PCSM in men treated with androgen deprivation therapy (ADT) compared to surgery, but could not observe an association between ADT and CVDM. The probability of PCSM was significantly higher for patients on active surveillance or watchful waiting, compared to surgery. Age and PCa risk categories were positively associated with risk of PCSM, whereas there was no evidence for an association with CVDM or OCM based on risk groups. ConclusionsOverall, men with PCa were more likely to die from non-PCa related outcomes. Nevertheless, the analyses showed a high proportion of PCSM among men on ADT, older men and men with a high-risk tumor. However, further research is needed to understand comprehensively the benefits of the respective treatments.

Abstract 3292: Cause-specific mortality of nonmetastatic prostate cancer patients

Abstract Background: Prostate cancer (PCa) is the most frequent incident cancer in men in Switzerland. One of the major challenges in the treatment of PCa is to reliably distinguish between patients at risk of dying as a direct result of the disease and those more likely to die of other causes. The purpose of this study was to assess the associations of age and risk group based on stage, grade and PSA level with primary treatment of non-metastatic PCa patients, and to evaluate whether this treatment was associated with cardiovascular death or prostate cancer specific mortality (PCSM). Methods: Population-based data from the Cancer Registry of Zurich and Zug in Switzerland were used. We identified 1919 non-metastatic PCa patients diagnosed between 2000 and 2009 who were living in the City of Zurich. PCa risk groups were stratified into three groups based on T stage, Gleason score and initial PSA concentration as described by D’Amico (low-risk: T1-2a, and Gleason score &amp;lt;=6, and PSA &amp;lt;=10 ng/mL; intermediate risk: T2b and/or Gleason score = 7 and/or PSA &amp;gt; 10 and &amp;lt;=20; high-risk: &amp;gt;= T2c or Gleason score 8-10 or PSA &amp;gt; 20). Multiple imputation methods were applied to deal with missing risk group information. We distinguished between surgical procedures, radiotherapy, androgen deprivation therapy (ADT), active surveillance, and watchful waiting. Fine and Gray competing risk regression analysis was used to estimate sub-distribution hazard ratios for the outcomes cardiovascular death, PCSM or other-cause mortality. Results: Unadjusted competing risk model revealed an increased risk of cardiovascular death for patients with ADT (HR=2.00 [1.27 - 3.14]), or watchful waiting compared to surgery (HR = 2.19 [1.58 - 3.02]). However, after adjustment for age and risk group, an increased risk of cardiovascular death was no longer observed (ADT HR=1.51 [0.93 - 2.46], watchful waiting HR = 1.31 [0.91 - 1.89]). Only men ≥80 years of age still had an increased risk of cardiovascular death. Furthermore, we observed an increased adjusted risk of PCSM in men with ADT (HR=2.84 [1.97 - 4.01]) or under watchful waiting (HR=1.78 [1.29 - 2.46]) compared to surgery, for men ≥70 years (HR= 4.18 [2.18 - 8.00]) compared to men &amp;lt; 70 years old, and for patients with intermediate risk (HR=2.69 [1.34 - 5.39]) and high risk (HR=6.37 [3.30 - 12.30]) compared to patients with low risk. Discussion: The study suggests that ADT use for non-metastatic PCa patients may not be associated with an increased risk of cardiovascular death in general, but with an increased risk of PCSM. This is likely explained by the more frequent ADT use in older men and in men with a high-risk PCa. In addition, we observed that older men and men with an intermediate- or high-risk PCa had an increased risk of PCSM. Citation Format: Katarina Matthes, Giulia Pestoni, Dimitri Korol, Mieke Van Hemelrijck, Sabine Rohrmann. Cause-specific mortality of nonmetastatic prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3292. doi:10.1158/1538-7445.AM2017-3292

NADiA ProsVue prostate-specific antigen slope, CAPRA-S, and prostate cancer--specific survival after radical prostatectomy.

To assess whether NADiA ProsVue prostate-specific antigen slope, a prognostic biomarker for identifying men at a reduced risk of clinically recurrent prostate cancer after radical prostatectomy, is prognostic for prostate cancer--specific mortality (PCSM) and other outcomes. We examined long-term outcome in the cohort of 304 men selected for the ProsVue 510(k) clinical trial. We assessed the prognostic value of a ProsVue result ≤ 2.0 pg/mL/mo and pathologic risk stratified by the Cancer of the Prostate Risk Assessment Postsurgical nomogram for a reduced risk of prostate cancer--specific survival. We also assessed its value for predicting clinical outcome in men given salvage treatment for biochemical recurrence. Efficacy was assessed using univariate and multivariate Cox regression and the Kaplan-Meier analyses. Median (interquartile range) overall survival for the groups of men with a ProsVue slope result ≤ 2.0 and >2.0 pg/mL/mo were 11.0 (9.4-12.9) and 9.2 (4.9-11.6) years, respectively. The ProsVue univariate hazard ratio (95% confidence interval) for PCSM was 20.6 (6.8-62.7), with P <.0001 for a ProsVue result >2.0 pg/mL/mo vs a result ≤ 2.0 pg/mL/mo. The multivariate hazard ratio of ProsVue adjusted by Cancer of the Prostate Risk Assessment Postsurgical nomogram remained significant (16.7 [4.7-58.6]; P <.0001). The inverse of the hazard ratio translates to a 94.0% risk reduction for PCSM for men with a ProsVue result ≤ 2.0 pg/mL/mo. Salvage treatment for biochemical recurrence did not significantly reduce the hazard of clinical recurrence or PCSM; however, this is based on only 18 events. A NADiA ProsVue slope result ≤ 2.0 pg/mL/mo was prognostic for a reduced risk of PCSM in men after radical prostatectomy.

Greatest percent involved core length and the risk of death from prostate cancer in men with highest Gleason score 7 or higher.

164 Background: Men with highest Gleason Score (GS) ≥ 7 and a lower GS (Combo GS) have a decreased risk of prostate cancer (PC) specific mortality (PCSM) following radiation therapy (RT) or RT and androgen deprivation therapy (ADT). Whether this risk is modulated based on the greatest percent involved core length (GPC) is unknown and investigated in the current study. Methods: The study cohort consisted of 333 men with GS ≥ 7 PC consecutively treated between 12/1989 and 7/2000 using RT (n = 268; 80%) or RT and 6 months of ADT (n = 65; 20%). Biopsy core and tumor lengths were used to calculate the GPC. Competing risks regression assessed whether increasing GPC was associated with an increased risk of PCSM in men with or without ComboGS adjusting for prognostic factors, age, and treatment. Results: After a median follow-up of 5.36 years (IQR: 3.22-7.61 years) 92 (28%) men died, 28 (30%) from PC. Increasing GPC was significantly associated with an increased risk of PCSM (AHR: 1.02; 95%CI: 1.00, 1.03; p=0.02) (Table). Men with GPC ≥ 50% vs. &lt; 50% had significantly higher estimates of PCSM when ComboGS was present (p&lt; 0.001) vs. absent (p=0.55). Of the 127 men with ComboGS and GPC &lt; 50%, 83% were treated with RT alone and 2 PC deaths were observed; none in men with GS 7 and favorable intermediate-risk PC. Conclusions: Men treated with RT for ComboGS, GPC &lt; 50%, GS 7 and favorable intermediate-risk PC may not require ADT to reduce the risk of PCSM. [Table: see text]

Aspirin Use and the Risk of Prostate Cancer Mortality in Men Treated With Prostatectomy or Radiotherapy

Experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, but clinical data have been limited. We investigated whether use of ACs was associated with the risk of death from prostate cancer. This study comprised 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor database with localized adenocarcinoma of the prostate treated with radical prostatectomy (RP) or radiotherapy (RT). Of them, 2,175 (37%) were receiving ACs (warfarin, clopidogrel, enoxaparin, and/or aspirin). The risk of prostate cancer-specific mortality (PCSM) was compared between the AC and non-AC groups. After a median follow-up of 70 months, risk of PCSM was significantly lower in the AC group compared with the non-AC group (3% v 8% at 10 years; P < .01). The risks of disease recurrence and bone metastasis were also significantly lower. In a subgroup analysis by clinical risk category, the reduction in PCSM was most prominent in patients with high-risk disease (4% v 19% at 10 years; P < .01). The benefit from AC was present across treatment modalities (RT or RP). Analysis by type of AC medication suggested that the PCSM reduction was primarily associated with aspirin. Multivariable analysis indicated that aspirin use was independently associated with a lower risk of PCSM (adjusted hazard ratio, 0.43; 95% CI, 0.21 to 0.87; P = .02). AC therapy, particularly aspirin, was associated with a reduced risk of PCSM in men treated with RT or RP for prostate cancer. The association was most prominent in patients with high-risk disease.

Hormonal Therapy or External-Beam Radiation With Brachytherapy and the Risk of Death From Prostate Cancer in Men With Intermediate Risk Prostate Cancer

PurposeTo determine whether external-beam radiotherapy (EBRT) improves disease control compared with supplemental androgen suppression therapy (AST) in men with intermediate-risk prostate cancer who are being treated with brachytherapy. Patients and MethodsA total of 807 men with intermediate-risk prostate cancer (T2bNXM0, Gleason ≤7, prostate-specific antigen [PSA] <20 ng/mL; or cT1c-T2bNXM0, Gleason 7) were consecutively treated with either AST and brachytherapy or EBRT and brachytherapy, between 1997 and 2007, and were followed up until September 21, 2007. A Fine and Gray competing risks multivariable regression model was used to assess whether AST or radiotherapy dose escalation reduced the risk of prostate-cancer–specific mortality (PCSM) when adjusting for age, PSA, Gleason score, and tumor category. ResultsTreatment with brachytherapy and with EBRT was associated with a significant increase in the risk of PCSM compared with brachytherapy and AST (adjusted hazard ratio [HR] 4.027 [95% CI, 1.168-13.89]; P = .027) after adjusting for age and prostate cancer prognostic factors. A Gleason score of 4+3 and increasing PSA were associated with worse PCSM (adjusted HR 8.882 [95% CI, 1.095-72.04]; P = .041; and adjusted HR 8.029 [95% CI, 2.38-28.8]; P = .0014, respectively). ConclusionSupplemental AST use compared with EBRT is associated with a lower risk of PCSM in men with intermediate-risk PC undergoing brachytherapy. Prospective validation in a randomized controlled trial is needed.

Comorbidity and mortality results from a randomized prostate cancer screening trial.

Estimates of prostate cancer-specific mortality (PCSM) were similar for men randomly assigned to intervention compared with usual care on the Prostate, Lung, Colorectal and Ovarian PC screening study. However, results analyzed by comorbidity strata remain unknown. Between 1993 and 2001, of 76,693 men who were randomly assigned to usual care or intervention at 10 US centers, 73,378 (96%) completed a questionnaire that inquired about comorbidity and prostate-specific antigen (PSA) testing before random assignment. Fine and Gray's multivariable analysis was performed to assess whether the randomized screening arm was associated with the risk of PCSM in men with no or minimal versus at least one significant comorbidity, adjusting for age and prerandomization PSA testing. After 10 years of follow-up, 9,565 deaths occurred, 164 from PC. A significant decrease in the risk of PCSM (22 v 38 deaths; adjusted hazard ratio [AHR], 0.56; 95% CI, 0.33 to 0.95; P = .03) was observed in men with no or minimal comorbidity randomly assigned to intervention versus usual care, and the additional number needed to treat to prevent one PC death at 10 years was five. Among men with at least one significant comorbidity, those randomly assigned to intervention versus usual care did not have a decreased risk of PCSM (62 v 42 deaths; AHR, 1.43; 95% CI, 0.96 to 2.11; P = .08). Selective use of PSA screening for men in good health appears to reduce the risk of PCSM with minimal overtreatment.

Risk of Death From Prostate Cancer After Brachytherapy Alone or With Radiation, Androgen Suppression Therapy, or Both in Men With High-Risk Disease

We estimated the risk of prostate cancer (PC) -specific mortality (PCSM) after brachytherapy alone or in conjunction with androgen suppression therapy (AST), external-beam radiation therapy (EBRT), or both in men with high-risk PC. The study cohort comprised 1,342 men with a prostate-specific antigen level more than 20 ng/mL and clinical T3 or 4 and/or Gleason score 8 to 10 disease. Competing risks multivariable regression was performed to estimate the risk of PCSM in men treated with brachytherapy alone or with supplemental AST, EBRT, or both, adjusting for age, year of treatment, and known PC prognostic factors. Despite higher baseline probabilities of PCSM after a median follow-up of 5.1 years, there was a significant reduction in the risk of PCSM (adjusted hazard ratio [AHR], 0.32; 95% CI, 0.14 to 0.73; P = .006) in men treated with brachytherapy and both AST and EBRT as compared with neither. When compared with brachytherapy alone, a significant decrease in the risk of PCSM was not observed in men treated with either supplemental AST (AHR, 0.63; 95% CI, 0.27 to 1.47; P = .28) or EBRT (AHR, 0.57; 95% CI, 0.21 to 1.52; P = .26). There was a near-significant reduction (AHR, 0.53; 95% CI, 0.27 to 1.07; P = .079) in the risk of PCSM in men treated with tri- as compared with bimodality therapy. Supplemental AST and EBRT but not either supplement compared with brachytherapy alone was associated with a decreased risk of PCSM in men with high-risk PC.