Prostate Cancer-specific Mortality Research Articles

Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies

BackgroundThe association of adiposity with prostate cancer specific mortality remains unclear. We examined how adiposity relates to fatal prostate cancer and described the cross-sectional associations of commonly used adiposity measurements with adiposity estimated by imaging in UK Biobank. We also conducted a dose-response meta-analysis to integrate the new data with existing prospective evidence.Methods218,237 men from UK Biobank who were free from cancer at baseline were included. Body mass index (BMI), total body fat percentage (using bioimpedance), waist circumference (WC) and waist-to-hip ratio (WHR) were collected at recruitment. Risk of dying from prostate cancer (primary cause) by the different adiposity measurements was estimated using multivariable-adjusted Cox proportional hazards models. Results from this and other prospective cohort studies were combined in a dose-response meta-analysis.ResultsIn UK Biobank, 661 men died from prostate cancer over a mean follow-up of 11.6 years. In the subsample of participants with magnetic resonance imaging and dual-energy X-ray absorptiometry, BMI, body fat percentage and WC were strongly associated with imaging estimates of total and central adiposity (e.g. visceral fat, trunk fat). The hazard ratios (HR) for prostate cancer death were 1.07 (95% confidence interval = 0.97–1.17) per 5 kg/m2 higher BMI, 1.00 (0.94–1.08) per 5% increase in total body fat percentage, 1.06 (0.99–1.14) per 10 cm increase in WC and 1.07 (1.01–1.14) per 0.05 increase in WHR. Our meta-analyses of prospective studies included 19,633 prostate cancer deaths for BMI, 670 for body fat percentage, 3181 for WC and 1639 for WHR, and the combined HRs for dying from prostate cancer for the increments above were 1.10 (1.07–1.12), 1.03 (0.96–1.11), 1.07 (1.03–1.11), and 1.06 (1.01–1.10), respectively.ConclusionOverall, we found that men with higher total and central adiposity had similarly higher risks of prostate cancer death, which may be biologically driven and/or due to differences in detection. In either case, these findings support the benefit for men of maintaining a healthy body weight.

Anti-epileptic drugs and prostate cancer-specific mortality compared to non-users of anti-epileptic drugs in the Finnish Randomized Study of Screening for Prostate Cancer

BackgroundDrugs with histone deacetylase inhibitory (HDACi) properties have shown to decrease prostate cancer (PCa) cell growth in vitro.MethodsA cohort of 9261 PCa cases from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) was used to evaluate prostate cancer-specific mortality in men using anti-epileptic drugs (AEDs). A national subscription database was used to obtain information on medication use. Cox regression with AED use as a time-dependent variable was used to analyse prostate cancer mortality in men using AEDs compared to non-users, and in men using HDACi AEDs compared to users of other AEDs. The analysis was adjusted for age, screening trial arm, PCa risk group, primary treatment of PCa, Charlson co-morbidity score and concomitant use of other drugs.ResultsThe use of AEDs, in general, was associated with an increased risk of PCa death. The use of HDACi AEDs was not significantly associated with decreased PCa mortality compared to use of other AEDs (HR 0.61, 95% CI 0.31–1.23).ConclusionsAED usage is associated with elevated PCa mortality compared to non-users, likely reflecting the differences between men with epilepsy and those without. No benefit was observed from HDACi drugs compared to other AEDs.

MP57-19 VALIDATION OF PROSTATE SPECIFIC ANTIGEN DOUBLING TIME KINETICS FOLLOWING RADICAL PROSTATECTOMY TO GUIDE ACTIVE OBSERVATION AND INTERVENTION

You have accessJournal of UrologyCME1 May 2022MP57-19 VALIDATION OF PROSTATE SPECIFIC ANTIGEN DOUBLING TIME KINETICS FOLLOWING RADICAL PROSTATECTOMY TO GUIDE ACTIVE OBSERVATION AND INTERVENTION Erica Huang, Linda My Huynh, Adam Gordon, Ryan Chandhoke, Blanca Morales, Douglas Skarecky, Joshua Tran, and Thomas Ahlering Erica HuangErica Huang More articles by this author , Linda My HuynhLinda My Huynh More articles by this author , Adam GordonAdam Gordon More articles by this author , Ryan ChandhokeRyan Chandhoke More articles by this author , Blanca MoralesBlanca Morales More articles by this author , Douglas SkareckyDouglas Skarecky More articles by this author , Joshua TranJoshua Tran More articles by this author , and Thomas AhleringThomas Ahlering More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002640.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Biochemical recurrence (BCR) following radical prostatectomy (RP) has limited ability to predict metastatic progression or prostate cancer specific mortality (PCSM). In our experience, a significant number of men with BCR have non-lethal BCR that can be safely observed based on PSA doubling time (DT) and subsequent DT change without radiation (RT) and/or androgen deprivation therapy (ADT). The present study seeks to validate the use of DT kinetics to direct active observation (AO) and intervention. METHODS: A retrospective cohort analysis of 1864 men who underwent RP between June 2002 and September 2019 was conducted. Patients were assessed for treatment intervention (RT and/or ADT) versus AO with DT kinetics. Our main outcome was the predictive value of multivariate regression models for no treatment via ROC analysis. Secondary outcomes were PCSM via Kaplan-Meier analysis. RESULTS: 407/1864 (21.8%) men experienced BCR (PSA >0.2 ng/dl, x2), with median follow-up of 7.6 years (IQR 3.3-11.9) (Table 1). In multivariable analysis, DT >12 months (OR: 8.93, 95%CI: 4.53, 17.6) and increasing DT (OR: 5.49, 95%CI: 2.81, 10.71) were significant predictors for continued observation without treatment (p <0.001), while pGGG, p-stage, age, and preoperative PSA were not. This model was an excellent predictor for continued no treatment (AUC=0.83). No patients with DT >12 months, increasing DT experienced PCSM (Figure 1). CONCLUSIONS: In our experience, one third of patients with BCR were observed without RT and/or ADT, with 0% PCSM at mean 7.6 years follow-up. DT >12 months and increasing DT were excellent predictors of no need for treatment. We introduce PSA kinetics as a means for guiding need and/or no need for treatment intervention. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e989 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Erica Huang More articles by this author Linda My Huynh More articles by this author Adam Gordon More articles by this author Ryan Chandhoke More articles by this author Blanca Morales More articles by this author Douglas Skarecky More articles by this author Joshua Tran More articles by this author Thomas Ahlering More articles by this author Expand All Advertisement PDF DownloadLoading ...

PD03-09 THE NATURAL HISTORY OF A DETECTABLE SERUM PSA AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 May 2022PD03-09 THE NATURAL HISTORY OF A DETECTABLE SERUM PSA AFTER RADICAL PROSTATECTOMY Julie A. Szymaniak, Samuel L. Washington, Janet E. Cowan, Matthew R. Cooperberg, Peter E. Lonergan, Hao G. Nguyen, and Peter R. Carroll Julie A. SzymaniakJulie A. Szymaniak More articles by this author , Samuel L. WashingtonSamuel L. Washington More articles by this author , Janet E. CowanJanet E. Cowan More articles by this author , Matthew R. CooperbergMatthew R. Cooperberg More articles by this author , Peter E. LonerganPeter E. Lonergan More articles by this author , Hao G. NguyenHao G. Nguyen More articles by this author , and Peter R. CarrollPeter R. Carroll More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002518.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical prostatectomy (RP) is a common form of definitive treatment for men with localized prostate cancer. A detectable postoperative serum PSA is thought to represent treatment failure and such patients are often offered salvage therapy while those with an undetectable PSA are monitored closely. We aim to better characterize the natural history of patients with a delayed detectable PSA after RP using a “ultrasensitive” cut point (0.03 ng/ml), a more contemporary value. METHODS: A retrospective analysis of men who underwent RP for non-metastatic prostate cancer at the University of California, San Francisco from 2000 to 2021, who consented for research, and had extensive follow-up was performed. Each participant in the delayed group reached an undetectable post-operative PSA within 6 months. The primary outcome was biochemical recurrence, defined as 2 consecutive PSA>=0.03 starting 6 months after surgery. Secondary outcomes were salvage treatment, post-salvage treatment, metastasis (nodal or bone) free survival (MFS), prostate cancer specific mortality (PCSM), and all-cause mortality (ACM). RESULTS: From our cohort of 3132 patients, we identified 2684 men who had an undetectable post-op PSA. The median follow-up after RP was 55 months. Subsequently, 646 men had a delayed detectable PSA at a median time of 29 months (IQR 16, 54). PSA at time of failure was <0.1 for 63.9% of men, 0.1-0.2 for 19.8%, and >0.2 for 16.1%. Of those with a delayed detectable PSA, 42% underwent salvage treatment within 10 years after RP. PSA at diagnosis (HR 1.02, CI 1.01-1.03, p=0.003), high Decipher score (HR 1.56, CI 1.02-2.38, p=0.04), and surgical CAPRA-S (HR 1.13, CI 1.06-1.2, p=0.0003) were associated with risk of receiving salvage treatment. In terms of treatment type, 95% received radiation +/- ADT, 4.4% received ADT alone, and 0.4% had advanced treatment. After salvage treatment, 63% of men had recurrent PSA failure within 10 years. In this subcohort, 20% had radiation, 76% received hormonal therapy, and 3.3% had advanced treatment. Overall, MFS was 95%, PCSM 2%, and ACM 5% at 10 years. For those with recurrent PSA failure after salvage treatment, MFS was 70%, PCSM 22% and ACM 22% at 10 years' time. CONCLUSIONS: Men who develop a detectable serum PSA >6 months post-operatively may have excellent long-term outcomes. Such information can be used to assess the timing and type of additional treatment. Source of Funding: Goldberg-Benioff Program in Translational Cancer Biology in the UCSF Department of Urology © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e45 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Julie A. Szymaniak More articles by this author Samuel L. Washington More articles by this author Janet E. Cowan More articles by this author Matthew R. Cooperberg More articles by this author Peter E. Lonergan More articles by this author Hao G. Nguyen More articles by this author Peter R. Carroll More articles by this author Expand All Advertisement PDF DownloadLoading ...

EDITORIAL COMMENT

Historical and contemporary data consistently show Black men have a higher incidence of prostate cancer and experience worse oncologic outcomes.1 While the precise cause of these disparities remains unclear, a growing number of publications indicate that socioeconomic status (SES) and environmental exposures, also referred to as social determinants of health (SDOH), are substantial drivers of these differences. In this article, DeRouen et al. examine the relationship between neighborhood archetypes and racial/ethnic disparities seen in prostate cancer-specific mortality (PCSM) and overall survival (OS).

A Novel Risk Score (P-score) Based on a Three-Gene Signature, for Estimating the Risk of Prostate Cancer-Specific Mortality.

PurposeTo develop and validate a risk score (P-score) algorithm which includes previously described three-gene signature and clinicopathological parameters to predict the risk of death from prostate cancer (PCa) in a retrospective cohort.Patients and MethodsA total of 591 PCa patients diagnosed between 2003 and 2008 in Stockholm, Sweden, with a median clinical follow-up time of 7.6 years (1–11 years) were included in this study. Expression of a three-gene signature (IGFBP3, F3, VGLL3) was measured in formalin-fixed paraffin-embedded material from diagnostic core needle biopsies (CNB) of these patients. A point-based scoring system based on a Fine-Gray competing risk model was used to establish the P-score based on the three-gene signature combined with PSA value, Gleason score and tumor stage at diagnosis. The endpoint was PCa-specific mortality, while other causes of death were treated as a competing risk. Out of the 591 patients, 315 patients (estimation cohort) were selected to develop the P-score. The P-score was subsequently validated in an independent validation cohort of 276 patients.ResultsThe P-score was established ranging from the integers 0 to 15. Each one-unit increase was associated with a hazard ratio of 1.39 (95% confidence interval: 1.27–1.51, p < 0.001). The P-score was validated and performed better in predicting PCa-specific mortality than both D’Amico (0.76 vs 0.70) and NCCN (0.76 vs 0.71) by using the concordance index for competing risk. Similar improvement patterns are shown by time-dependent area under the curve. As demonstrated by cumulative incidence function, both P-score and gene signature stratified PCa patients into significantly different risk groups.ConclusionWe developed the P-score, a risk stratification system for newly diagnosed PCa patients by integrating a three-gene signature measured in CNB tissue. The P-score could provide valuable decision support to distinguish PCa patients with favorable and unfavorable outcomes and hence improve treatment decisions.

MP55-08 HIGH INTENSITY FOCUSED ULTRASOUND AND CRYOABLATION FOCAL THERAPY FOR INTERMEDIATE RISK PROSTATE CANCER: ONCOLOGIC AND FUNCTIONAL OUTCOMES

You have accessJournal of UrologyCME1 May 2022MP55-08 HIGH INTENSITY FOCUSED ULTRASOUND AND CRYOABLATION FOCAL THERAPY FOR INTERMEDIATE RISK PROSTATE CANCER: ONCOLOGIC AND FUNCTIONAL OUTCOMES Masatomo Kaneko, Alireza Ghoreifi, Samuel Peretsman, Dordaneh Sugano, Giovanni Cacciamani, Amir Lebastchi, Suzanne Palmer, Manju Aron, Osamu Ukimura, Inderbir Gill, and Andre Abreu Masatomo KanekoMasatomo Kaneko More articles by this author , Alireza GhoreifiAlireza Ghoreifi More articles by this author , Samuel PeretsmanSamuel Peretsman More articles by this author , Dordaneh SuganoDordaneh Sugano More articles by this author , Giovanni CacciamaniGiovanni Cacciamani More articles by this author , Amir LebastchiAmir Lebastchi More articles by this author , Suzanne PalmerSuzanne Palmer More articles by this author , Manju AronManju Aron More articles by this author , Osamu UkimuraOsamu Ukimura More articles by this author , Inderbir GillInderbir Gill More articles by this author , and Andre AbreuAndre Abreu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002634.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To evaluate oncologic and functional outcomes following High Intensity Focused Ultrasound (HIFU) and Cryoablation (CRYO) focal therapy (FT) for localized prostate cancer (PCa). METHODS: We identified consecutive patients who underwent hemi-gland HIFU (h-HIFU) or hemi-gland CRYO (h-CRYO) FT as primary treatment for D’Amico intermediate risk PCa (IRB# HS-17-00749). Patients were selected by 12-core systematic and target biopsy and had unilateral index lesion. Follow up biopsy (FU-PBx) was performed from 6-12M and every 2Y thereafter. Primary endpoint was Treatment Failure (TF) defined as radical (any whole-gland) treatment, systemic therapy, metastases, or PCa-specific mortality. Secondary endpoints were survival-free from i) biochemical failure (BF, PSA nadir+2 ng/mL); ii) Grade Group (GG) ≥2 on FU-PBx, iii) repeat FT, iv) radical treatment, and v) systemic therapy. Kaplan-Meier method was used for survival evaluation. International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and continence (zero pad) were also evaluated. Statistically significant if p <0.05. RESULTS: 184 patients met inclusion criteria: 121 (66%) h-CRYO and 63 (34%) h-HIFU. The baseline characteristics were comparable among h-HIFU vs h-CRYO, respectively, as follows: median age (65 vs 67 Y, p =0.15), PSA (5.9 vs 6.7 ng/mL, p = 0.081), PSA density (0.18 vs 0.17 ng/mL2, p = 0.61), number of positive cores (3 vs 3, p=0.14) and maximum PCa core % (50% vs 50%, p=0.59). h-CRYO had higher rate of GG3, as follows: GG1 (2% vs 7%), GG2 (79% vs 50%) and GG3 (19% vs 42%); p <0.001. The median follow up was longer for h-CRYO (30 M) vs h-HIFU (24M); p=0.005. PSA nadir was 1.1 ng/mL for h-HIFU vs 0.91 ng/mL for h-CRYO, p=0.53. The 3-year TF-free survival was: 88% for h-HIFU and 95% for h-CRYO, p=0.32. The 3-year free survival was, for h-HIFU vs h-CRYO, respectively: BF (80% vs 70%, p=0.89); GG≥2 on FU-PBx (63% vs 90%, p <0.001), repeat FT (93% vs 98%, p=0.40), radical treatment (87% vs 99%, p=0.04) and systemic therapy (100% vs 96%, p=0.23). One patient on h-CRYO developed bone metastases, but no patient died. Median difference from pre- to post-FT IPSS (0 vs 1.5; p=0.99) and IIEF-5 (0 vs 2; p=0.14) were similar for h-HIFU vs h-CRYO, respectively. Continence was maintained in 100% h-HIFU vs 98% h-CRYO, p=1.00. CONCLUSIONS: Hemi-gland HIFU or CRYO for intermediate risk PCa provide acceptable short-medium term oncologic outcomes with excellent function outcomes. Hemi-gland CRYO provided longer radical treatment-free survival than hemi-gland HIFU. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e940 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masatomo Kaneko More articles by this author Alireza Ghoreifi More articles by this author Samuel Peretsman More articles by this author Dordaneh Sugano More articles by this author Giovanni Cacciamani More articles by this author Amir Lebastchi More articles by this author Suzanne Palmer More articles by this author Manju Aron More articles by this author Osamu Ukimura More articles by this author Inderbir Gill More articles by this author Andre Abreu More articles by this author Expand All Advertisement PDF DownloadLoading ...

This Month in Adult Urology

This Month in Adult Urology

Long-term outcomes of whole gland high-intensity focused ultrasound for localized prostate cancer.

To report the 10-year oncologic and functional outcomes of whole-gland HIFU as first-line treatment for localized prostate cancer (PCa). Patients were retrospectively included between January 2005 and July 2018 from a prospectively maintained database at a single academic institution. No patient underwent androgen deprivation therapy prior to HIFU. Primary endpoint was biochemical recurrence-free survival (BRFS). Secondary oncological endpoints included salvage treatment-free survival (STFS), cancer-specific survival (CSS) and overall survival (OS). A total of 97 patients met our inclusion criteria and were included in the final analysis. According to D'Amico classification, the numbers of patients with low-, intermediate-, and high-risk disease were 38 (39.2%), 52 (53.6%), and 7 (7.2%). A total of 21 (21.6%) patients received salvage treatment at a mean of 4.1years (± 2.8) after HIFU. The 10-year OS, CSS and BRFS rates were 91.8%, 100% and 40.3% in the overall cohort, respectively. In multivariate analysis, predictive factors for biochemical recurrence were intermediate-risk group (RR = 2.065; 95% CI 1.008-4.230; p = 0.047) and PSA nadir > 0.5ng/mL (RR = 4.963; 95% CI 2.251-10.947; p < 0.001). Symptoms related to bladder outlet obstruction were the most frequently recorded adverse events. In multivariate analysis, positive biopsy on the prostatic apex was predictor of obstructive complications (RR = 3.2, 95% CI 1.092-9.476, p = 0.034). Only four patients developed severe urinary incontinence (> 1 pad/day). HIFU showed low PCa-specific mortality, but biochemical recurrence rates were highly variable among patients. Future studies are needed to improve patient selection.

Absolute Prostate Specific Antigen after 6 Months of Androgen Deprivation Therapy Is a Predictor of Overall and Cancer-Specific Mortality in Men with Hormone-Sensitive Prostate Cancer.

We sought to determine if absolute prostate specific antigen (PSA) value after 6 months of androgen deprivation therapy (ADT) is predictive of subsequent survival in patients with prostate adenocarcinoma. We performed a retrospective review of men receiving care within the Veterans Health Administration who initiated ADT for prostate adenocarcinoma. We used low- (≤0.2 ng/ml), intermediate- (>0.2 to 4 ng/ml) and high-risk (>4 ng/ml) absolute PSA values after 6-9 months of ADT, previously described in Southwest Oncology Group trial 9346. The primary endpoints were all-cause mortality and prostate cancer-specific mortality (PCSM). Kaplan-Meier survival curves for each PSA category were estimated and log-rank test was conducted. We employed Cox regression analysis adjusted for covariates and inverse propensity score weights associated with PSA categories to estimate the PSA category association with PCSM and all-cause mortality. We identified 9,170 patients in our cohort. Following ADT induction, 3,508 patients had low, 3,419 had intermediate and 2,243 had high PSA values. Two- and 5-year survival rates for low, intermediate and high PSA groups were 93.9% and 85.2% vs 88.6% and 71.2% vs 63.6% and 38.6%, respectively (p <0.0001). Patients in the high and intermediate PSA categories had a 15-fold and 3-fold higher risk of PCSM compared to those with PSA <0.2 ng/ml (p <0.0001). Absolute PSA in hormone-sensitive prostate cancer after 6-9 months of ADT is a predictor of overall mortality and PCSM. This measure can rapidly assess the efficacy of new interventions in phase 2 clinical trials.

High Keratin-7 Expression in Benign Peri-Tumoral Prostatic Glands Is Predictive of Bone Metastasis Onset and Prostate Cancer-Specific Mortality.

Simple SummaryKeratin-7 overexpression has been associated with poor prognosis in several cancers. To determine its prognostic relevance in prostate cancer, cohorts of patients presenting with localized or advanced tumors were investigated by either immunohistochemistry or immunofluorescence. Keratin-7 immunostaining was absent in localized tumors and rare in advanced tumors. By contrast, it was abundantly detected in basal cells within benign glands surrounding localized tumors. Importantly, high keratin-7 expression in benign peri-tumoral glands was correlated with shorter bone metastasis-free survival and increased risk of cancer-specific mortality. This study establishes keratin-7 expression in localized prostate cancer specimens as a promising biomarker of disease progression.Background: New predictive biomarkers are needed to accurately predict metastasis-free survival (MFS) and cancer-specific survival (CSS) in localized prostate cancer (PC). Keratin-7 (KRT7) overexpression has been associated with poor prognosis in several cancers and is described as a novel prostate progenitor marker in the mouse prostate. Methods: KRT7 expression was evaluated in prostatic cell lines and in human tissue by immunohistochemistry (IHC, on advanced PC, n = 91) and immunofluorescence (IF, on localized PC, n = 285). The KRT7 mean fluorescence intensity (MFI) was quantified in different compartments by digital analysis and correlated to clinical endpoints in the localized PC cohort. Results: KRT7 is expressed in prostatic cell lines and found in the basal and supra-basal compartment from healthy prostatic glands and benign peri-tumoral glands from localized PC. The KRT7 staining is lost in luminal cells from localized tumors and found as an aberrant sporadic staining (2.2%) in advanced PC. In the localized PC cohort, high KRT7 MFI above the 80th percentile in the basal compartment was significantly and independently correlated with MFS and CSS, and with hypertrophic basal cell phenotype. Conclusion: High KRT7 expression in benign glands is an independent biomarker of MFS and CSS, and its expression is lost in tumoral cells. These results require further validation on larger cohorts.

Acceptance and efficacy of recommended adjuvant radiotherapy in patients with positive lymph nodes at radical prostatectomy: a preference-based study.

To investigate acceptance and efficacy of recommended adjuvant radiotherapy in patients with positive lymph nodes at radical prostatectomy. Among 495 patients with positive lymph nodes who consecutively underwent radical prostatectomy between 2007 and 2017, we investigated 347 patients who were recommended to undergo adjuvant radiotherapy by a multidisciplinary post-therapeutic tumor board and in whom information whether such treatment was eventually given was available. The median follow-up for censored patients was 5.4years. Univariate analyses were performed using Kaplan-Meier curves, Mantel-Haenszel hazard ratios and log rank tests. Proportional hazard models for competing risks were used for multivariable analyses. Adjuvant radiotherapy was independently associated with lower overall mortality and in high-risk patients (Gleason score 8-10 or three or more involved lymph nodes) also with lower prostate cancer-specific mortality. In patients with a Gleason score of 8-10 or three or more involved lymph nodes, the hazard ratio for adjuvant radiotherapy was 0.455 (95% confidence interval 0.257-0.806, p = 0.0069) for overall and 0.426 (95% confidence interval 0.201-0.902, p = 0.0259) for prostate cancer-specific mortality. Among patients receiving adjuvant radiotherapy, there was a trend to lower mortality when such treatment was combined with adjuvant androgen deprivation. Adjuvant radiotherapy decreased mortality in patients with positive lymph nodes at radical prostatectomy with further disease factors but not in patients with low-risk disease. Simultaneous androgen deprivation might increase efficacy. Multidisciplinary recommendations may possibly increase the use of adjuvant radiotherapy in this setting.

Serum thymidine kinase 1 concentration as a predictive biomarker in prostate cancer.

BackgroundThymidine kinase 1 (TK1) recycles DNA before cell division. We do not know if baseline blood concentrations of TK1 predict death in prostate cancer within 30 years.Our objective is to determine if there is an association between baseline levels of TK1 and future prostate cancer‐specific mortality.MethodsWith a “proof of concept” approach, we performed a nested case–control study among 1782 individuals screened for prostate cancer between 1988 and 1989. The concentration of TK1 was measured in frozen serum from 330 men, 36 of whom have died of prostate cancer.The primary endpoint was prostate cancer‐specific mortality and outcomes after 30 years were analyzed using logistic regression modeling odds ratios (Ors).ResultsThe estimated OR (adjusted for age) for dying from prostate cancer among the men who had a TK1 value in the upper tertile was 2.39 (95% confidence interval 1.02–5.63). The corresponding OR, regardless of the cause of death, was 2.81 (1.24–6.34).ConclusionsHigh levels of TK1 predicts death in prostate cancer within 30 years of follow‐up.

Long-Term Survival and Causes of Death After Diagnoses of Common Cancers in 3 Cohorts of US Health Professionals.

BackgroundFew studies investigated long-term overall survival and causes of death among men and women diagnosed with most commonly occurring cancers.MethodsWe estimated long-term (≥30-year) overall and cause-specific cumulative mortality for men diagnosed with prostate (n = 6873), lung and bronchus (n = 1290), colon and rectum (n = 1418), bladder (n = 1321), and melanoma (n = 2654) cancer in the Health Professionals Follow-up Study between 1986 and 2012 and women with breast (n = 18 280), lung and bronchus (n = 3963), colon and rectum (n = 3461), uterine corpus (n = 1641), and thyroid (n = 1103) cancer in the Nurses’ Health Study between 1976 and 2012 and Nurses’ Health Study II between 1989 and 2013.ResultsWe reported overall and cause-specific cumulative mortality of 30 years among men and 35 years among women. Among male cancer survivors, the 30-year cumulative cancer-specific mortality was 15.4% (95% confidence interval [CI] = 14.4% to 16.4%) for prostate, 83.5% (95% CI = 81.2% to 85.5%) for lung and bronchus, 37.0% (95% CI = 34.4% to 39.5%) for colon and rectum, 22.5% (95% CI = 20.0% to 25.0%) for urinary bladder, and 8.0% (95% CI = 6.9% to 9.1%) for melanoma. Among female cancer survivors, the 35-year cumulative cancer-specific mortality rate was 20.6% (95% CI = 19.7% to 21.6%) for breast, 83.5% (95% CI = 81.6% to 85.2%) for lung and bronchus, 39.6% (95% CI = 37.5% to 41.6%) for colon and rectum, 16.6% (95% CI = 14.7% to 18.6%) for uterine corpus, and 3.2% (95% CI = 2.1% to 4.3%) for thyroid. Except for lung cancer, most patients with common cancer were more likely to die from causes other than primary cancers. We observed 2 basic trends for cumulative cancer-specific mortality. The first is a sustained but nevertheless excess risk: Prostate or breast cancer-specific cumulative mortality continued to increase after diagnosis from 5 to 30 years or longer. The second is greatly diminished risk of index cancer-specific mortality following diagnosis 10 years or longer previously. For example, colorectal cancer–specific mortality increased by less than 4 percentage points between 10 and 30 or 35 years after diagnosis, and this finding also applied to lung, bladder, melanoma, uterine corpus, and thyroid cancer.ConclusionsExcept for lung cancer, patients diagnosed with common cancers were more likely to die from causes other than primary cancers. Patients with lung, colorectal, bladder, melanoma, uterine corpus, or thyroid cancer surviving longer than 10 years after diagnosis are unlikely to die from that disease.

Validating the association of adverse pathology with distant metastasis and prostate cancer mortality 20-years after radical prostatectomy.

To assess the association of adverse pathology (AP), defined as high-grade (≥ Gleason Grade Group 3) and/or non-organ confined disease, with long-term oncologic outcomes after radical prostatectomy (RP). Using a stratified cohort sampling design, we evaluated the association of AP with the risk of distant metastasis (DM) and prostate cancer-specific mortality (PCSM) up to 20 years after RP in 428 patients treated between 1987 to 2004. Cox regression of cause-specific hazards was used to estimate the absolute risk of both endpoints, with death from other causes treated as a competing risk. Additionally, subgroup analysis in patients with low and/or intermediate-risk disease, who are potentially eligible for active surveillance (AS), was performed. Within the cohort sample, 53% of men exhibited AP at time of RP, with median follow up of 15.5 years (IQR 14.6-16.6 years) thereafter. Adverse pathology was highly associated with DM and PCSM in the overall cohort (HR 12.30, 95% confidence interval [CI] 5.30-28.55, and HR 10.03, 95% CI 3.42-29.47, respectively, both P < 0.001). Adverse pathology was also highly associated with DM and PCSM in the low/intermediate-risk subgroup (HR 10.48, 95% CI 4.18-26.28, and 8.60, 95% CI 2.40-30.48, respectively, both P < 0.001). Adverse pathology at the time of RP is highly associated with future development of DM and PCSM. Accurate prediction of AP may thus be useful for individualizing risk-based surveillance and treatment strategies.

Radiation therapy after radical prostatectomy is associated with higher other-cause mortality

PurposeTo test the association between external beam radiotherapy (EBRT) after radical prostatectomy (RP) vs RP only on rates of other-cause mortality (OCM) in men with prostate cancer (PCa).Patients and methodsWithin the 2004–2016 Surveillance, Epidemiology, and End Results database, we identified 181,849 localized PCa patients, of whom 168,041 received RP only vs 13,808 who received RP + EBRT. Cumulative incidence plots displayed OCM between RP vs RP + EBRT after propensity score matching for age, PSA, clinical T- and N-stages, and biopsy Gleason scores. Multivariable competing risks regression models addressed OCM, accounting prostate cancer-specific mortality (CSM) as a competing event. Stratifications were made according to low- vs intermediate- vs high-risk groups and additionally according to age groups of ≤ 60, 61–70, and ≥ 71 years, within each risk group.ResultsIn low-, intermediate-, and high-risk patients, RP + EBRT rates were 2.7, 5.4 and 17.0%, respectively. After matching, 10-year OCM rates between RP and RP + EBRT were 7.7 vs 16.2% in low-, 9.4 vs 13.6% in intermediate-, and 11.4 vs 13.5% in high-risk patients (all p < 0.001), which, respectively, resulted in multivariable HR of 2.1, 1.3, and 1.2 (all p < 0.001). In subgroup analyses, excess OCM was recorded in low-risk RP + EBRT patients of all age groups (all p ≤ 0.03), but only in the older age group in intermediate-risk patients (61–70 years, p = 0.03) and finally, only in the oldest age group in high-risk patients (≥ 71 years, p = 0.02).ConclusionExcess OCM was recorded in patients exposed to RT after RP. Its extent was most pronounced in low-risk patients, decreased in intermediate-risk patients, and was lowest in high-risk patients.

Glycemic control was associated with nonprostate cancer and overall mortalities in diabetic patients with prostate cancer.

Diabetes mellitus (DM) can worsen the prognosis or survival in prostate cancer (PC) patients. We investigated whether glycemic control impacts mortality in PC patients with existing diabetes. All PC patients with or without preexisting DM were enrolled from 2006 to 2017. Mean hemoglobin A1c (HbA1c) values (<7%, 7%-9%, ≥9%) were used to represent glycemic control. Major outcomes included all-cause, PC-specific, and non-PC mortalities. Statistical analyses were performed using Cox regression models with adjusted mean HbA1c and other related confounders. A total of 831 PC patients were enrolled (non-DM group, n = 690; DM group with a record of mean HbA1c values, n = 141). Results showed that the DM group with mean HbA1c level ≥ 9% (n = 14) had significantly increased risk for all-cause and non-PC mortality (hazard ratio [HR], 3.09; 95% CIs, 1.15-8.32; p=0.025 and HR, 5.49; 95% CIs, 1.66-18.16; p = 0.005, respectively), but not for PC-specific mortality (HR, 1.03; 95% CIs, 0.13-8.44; p = 0.975), compared with the non-DM group. Our findings indicate that PC patients with DM who had a mean HbA1c level ≥ 9% had higher risks of all-cause and non-PC mortality compared with non-DM subjects. Further large and long-term studies are needed to verify the effect of glycemic control in PC patients with DM.

Localized prostate cancer: An analysis of the Centers for Disease Control and Prevention Breast and Prostate Cancer Data Quality and Patterns of Care study (CDC PoC-BP).

Limited evidence exists on the comparative effectiveness of local treatments for prostate cancer (PCa) due to the lack of generalizability. Using granular national data, we sought to examine the association between radical prostatectomy (RP) and intensity-modulated radiation therapy (IMRT) treatment and survival. Records were abstracted for localized PCa cases diagnosed in 2004 across seven state registries to identify patients undergoing RP (n=3019) or IMRT (n=667). Comorbidity was assessed by the Adult Comorbidity Evaluation-27 (ACE-27). Propensity score matching (PSM) was used to balance covariates between treatment groups. All-cause and PCa-specific mortality were primary endpoints. A subgroup analysis of patients with high-risk PCa (RP, n=89; IMRT, n=95) was conducted. Following PSM, matched patients (n=502 pairs) treated with either RP or IMRT were well-balanced with respect to covariates. With a median followup of 10.5 years (interquartile range [IQR] 9.9-11.0), the 11-year overall survival (OS) was 71.2% (95% confidence interval [CI] 66.9-75.8) for RP and 62.3% (95% CI 57.4-67.6) for IMRT. IMRT was associated with a 41% increased risk of all-cause mortality (hazard ratio [HR] 1.41, 95% CI 1.13-1.76) but not PCa-specific mortality (HR 1.75, 95% CI 0.84-3.64), as compared to RP. In patients with high-risk PCa, IMRT, as compared to RP, was not associated with a statistically significant difference in all-cause (HR 1.53, 95% CI 0.97-2.42) or PCa-specific mortality (HR 1.92, 95% CI 0.69-5.36). Despite a low mortality rate at 10 years and possible residual confounding, we found a significantly increased risk of all-cause mortality but no PCa-specific mortality associated with IMRT as compared to RP in this population-based study.

A Nationwide Analysis of Risk of Prostate Cancer Diagnosis and Mortality following an Initial Negative Transrectal Ultrasound Biopsy with Long-Term Followup.

Magnetic resonance imaging (MRI) targeted prostate biopsy has been shown to find many high-grade prostate cancers in men with concurrent negative transrectal ultrasound (TRUS) systematic biopsy. The oncologic risk of such tumors can be explored by looking at long-term outcomes of men with negative TRUS biopsy followed without MRI. The aim was to analyze the mortality after initial and second negative TRUS biopsy. All men who underwent initial TRUS biopsies between January 1, 1995 and December 31, 2016 in Denmark were included. A total of 37,214 men had a negative initial TRUS biopsy and 6,389 underwent a re-biopsy. Risk of cause-specific mortality was analyzed with competing risks. Diagnosis of Gleason score ≥7 prostate cancer following negative biopsies was analyzed with multivariable logistic regression including time to re-biopsy, prostate specific antigen (PSA), age and digital rectal examination. The 15-year prostate cancer-specific mortality was 1.9% (95% CI: 1.7-2.1). Prostate cancer-specific mortality was 1.3% (95% CI: 0.9-1.6) and 4.6% (95% CI: 3.4-5.8) for men with PSA <10 and >20 ng/ml, respectively. Of the TRUS re-biopsies 12% were Gleason score ≥7 and risk of Gleason score ≥7 increased with longer time to re-biopsy (p <0.001). Mortality after re-biopsy was similar to after initial biopsy. Men with negative TRUS biopsies have a very low prostate cancer-specific mortality, especially with PSA <10 ng/ml. This raises serious questions about the routine use of MRI targeting for initial prostate biopsy and suggests that MRI targeting should only be recommended for men with PSA >10 ng/ml after negative biopsy.

The Association of Prediagnostic Statin Use with Aggressive Prostate Cancer from the Multiethnic Cohort Study.

There is a growing body of evidence supporting the protective effect of statins on the risk of prostate cancer, in particular aggressive disease. Past research has mostly been conducted in North American cohorts of White men. In the multiethnic cohort (MEC), we investigated the association of prediagnostic statin use with the incidence and mortality of prostate cancer across five racial/ethnic groups (White, African American, Japanese American, Latino, and Native Hawaiian). Among 31,062 male participants who completed a detailed medication questionnaire, 31.4% reported use of statins, 2,748 developed prostate cancer, and 261 died from the disease. After adjusting for potential confounders, prediagnostic statin use was associated with a 32% lower risk of fatal prostate cancer [95% confidence interval (CI) = 0.50-0.91], with the inverse association suggested consistently across the five racial/ethnic groups. Moreover, an 11% lower risk of aggressive prostate cancer (95% CI = 0.76-1.03) was observed in statin users than in nonusers. We found no statistically significant association between prediagnostic statin use and total prostate cancer or nonaggressive disease. Prediagnostic statin use was suggestively associated with a 19% reduction in prostate cancer-specific mortality (95% CI = 0.59-1.10) and an 8% reduction in all-cause mortality (95% CI = 0.79-1.07). In the MEC, prediagnostic use of statin was associated with lower risks of aggressive forms of prostate cancer. Our findings provide further support for the potential benefits of statins in reducing the risk and mortality of prostate cancer, especially aggressive disease.