Validation of the Prostatype® P-score for predicting prostate cancer specific mortality in a multiethnic U.S. veterans cohort.

Combined Value of Validated Clinical and Genomic Risk Stratification Tools for Predicting Prostate Cancer Mortality in a High-risk Prostatectomy Cohort

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. < 50% had significantly higher estimates of PCSM when ComboGS was present (p< 0.001) vs. absent (p=0.55). Of the 127 men with ComboGS and GPC < 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 < 50%, GS 7 and favorable intermediate-risk PC may not require ADT to reduce the risk of PCSM. [Table: see text]

Introduction: Literature is limited regarding post-diagnostic dairy intake and prostate cancer survival. We evaluated dietary intake of total, high-fat, and low-fat dairy in relation to disease-specific and total mortality after prostate cancer diagnosis. Methods: We included 926 men from the Physicians' Health Study diagnosed with non-metastatic prostate cancer from 1982 to 2012, who completed a food frequency questionnaire a median of 5.1 years after diagnosis and were followed thereafter to assess mortality for a median of 9.9 years. Cox proportional hazards regression estimated the association between frequency categories of dairy intake and prostate cancer-specific and all-cause mortality. Person-years of follow-up were counted from the date of FFQ completion until death or end of follow-up, whichever came first. Models were adjusted for age at diagnosis, total energy intake, vigorous exercise, body mass index, smoking status, clinical stage, Gleason score, prostate specific antigen levels at diagnosis, indicators for prudent dietary pattern and western dietary pattern, and time interval between diagnosis and FFQ completion. Results: A total of 333 men died during follow-up, including 56 due to prostate cancer. Post-diagnosed dairy consumption was relatively limited, with medians of 1.7 servings/day for total dairy intake, 0.64 servings/day for high-fat dairy intake, and 1 serving/day for low-fat dairy intake. Men consuming dairy foods more than 3 times per day had a 76% higher risk of total mortality and a 144% increased risk of prostate cancer specific mortality than those consuming less than one dairy product per day (relative risk (RR)=1.76, 95% confidence interval (CI): 1.21, 2.55, Plinear-trend=0.001 for total mortality; RR=2.44, 95%CI: 0.99, 6.03, Plinear-trend=0.03 for disease-specific mortality). For total mortality, high-fat dairy intake (RR≥2 times/day vs <3 times/week=1.69, 95%CI: 1.11, 2.57) appeared to be more deleterious than low-fat dairy intake (RR≥2 times/day vs <3 times/week=1.25, 95%CI: 0.88, 1.77). The elevated risks of prostate cancer- specific mortality were comparable for high-fat dairy (RR≥2 times/day vs <3 times/week=1.81, 95% CI=0.71, 4.59) and low fat-dairy (RR≥2 times/day vs <3 times/week=1.83, 95%CI=0.75, 4.47). Conclusions: Among men diagnosed with non-metastatic prostate cancer, post-diagnostic dairy food intake was associated with greater prostate cancer-specific and all-cause mortality. The associations of low-fat and high-fat dairy were comparable for prostate cancer-specific mortality, while intake of high-fat dairy products may be particularly detrimental for total mortality. Citation Format: Meng Yang, Stacey A. Kenfield, Erin L. Van Blarigan, Kathryn M. Wilson, Julie L. Batista, Howard D. Sesso, Jing Ma, Meir J. Stampfer, Jorge E. Chavarro. Dairy intake in relation to disease-specific and total mortality after prostate cancer diagnosis. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A32.

70 Background: We evaluated the impact of a prior diagnosis of cancer on the risk of prostate cancer specific mortality (PCSM) and all cause mortality (ACM) in men with a diagnosis of non-metastatic prostate cancer (PC). Methods: Using the SEER population data registry, 166,104 men (median age: 66 [Interquartile range (IQR): 60 to 73 years]) diagnosed with prostate cancer (PC) between 2004 and 2007 comprised the study cohort. We used a Fine and Grays competing risks and Cox regression to evaluate the impact a prior cancer diagnosis (excluding non-melanoma skin cancer) had on the risk of PCSM and ACM adjusting for PSA level, Gleason score (GS), tumor (T) category, age at and year of diagnosis, race and whether initial treatment received was curative, non-curative or patients underwent active surveillance (AS) or watchful waiting (WW). Prior to the diagnosis of PC, 1,457 malignancies occurred at a median of 4.8 years. Results: After a median follow up of 2.75 years, 12,453 men died: 3,809 (30.6%) from PC. On multivariable analysis, advancing age in years was associated with an increased risk of PCSM as was Gleason score 8 to 10 PC and the use of WW/AS or non-curative therapy (all p values < 0.001). However, men with a prior cancer were significantly older (median age: 72 vs 66 years, p=0.001) and followed longer (median follow up: 3.0 vs 2.75 years, p < 0.001) and were more likely to have high-risk PC (30.1% vs 26.8%, p=0.01) based on the occurrence of Gleason 8 to 10 PC (19.2% vs 15.1%, P < 0.001) and underwent WW or AS more frequently (30.5% vs 22.5%, p<0.001). Despite these findings which would tend toward an increased risk of PCSM in these men, the adjusted risk of PCSM was significantly decreased in these men (Adjusted Hazard Ratio (AHR): 0.66 [95% Confidence Interval (CI): [0.45, 0.97]; p =0.033) while the risk of ACM was increased (AHR: 2.92 [95% CI: 2.64, 3.23]; p < 0.001) suggesting that competing risks and not curative PC treatment may be accounting for the reduction in the risk of PCSM. Conclusions: In men with a malignancy prior to the diagnosis of PC, a careful assessment of life expectancy is needed to decide on whether curative treatment for PC versus WW or AS is appropriate.

2292 PSA NADIR DURING ANDROGEN DEPRIVATION THERAPY PREDICTS ADVERSE PROSTATE CANCER SPECIFIC OUTCOMES: RESULTS FROM THE SEARCH DATABASE

Prostate cancer risk calculators: still much work ahead.

Hospitalization for osteoarthritis and prostate cancer specific mortality among Swedish men with prostate cancer

4571 Background: For men developing PSA failure after radical prostatectomy (RP), administration of immediate androgen deprivation therapy (ADT) has not been shown to improve survival compared to delaying ADT until evidence of metastatic disease. We evaluated factors influencing prostate cancer (PCa) specific mortality (PCSM) in a cohort of PSA era patients developing metastases after RP treated with delayed ADT. Methods: 3,658 men had RP by a single surgeon at Johns Hopkins Hospital from 4/82 until 6/05. 553 had PSA failure. 216 developed radiographically evident distant metastasis. Of these, 91 men formed the study cohort: initially treated during the PSA era (1987–2005), received ADT only after documented metastasis, and having complete data. 41 of these men died. Median failure times were estimated with the Kaplan-Meier method. Prognostic impact was estimated as the hazard ratio (HR) derived from the Cox proportional hazards model. Results: Median followup from RP was 10 yrs (range 2–18). Actuarial median failure times are: 1 yr from RP to PSA failure (range 1–11), 32 mos from PSA failure to metastasis (range 0–129), 79 mos from metastasis to death (range 7–181), and 13 yrs from RP to death (range 2–18). The following variables were significant prognostic factors for PCSM in univariate analyses: Pain at diagnosis of metastases (p < 0.01), time from RP to metastasis (p = 0.02), hematocrit at metastasis (p < 0.01) and PSADT <3 mos during the 2 years prior to metastasis (p < 0.01). A multivariable Cox proportional hazards model demonstrated the following independent predictors of PCSM: pain (HR = 10.5 p < 0.01), PSA at metastasis ≥100 ng/mL (HR = 5.3 p < 0.01) and PSADT < 3 months (HR = 7.1 p < 0.01). PSADT determined in the two years immediately after PSA failure (HR = 1.0 p = 0.37) and time from RP to bone metastasis (HR = 1.0 p = 0.80) were not independent predictors of PCSM. Conclusion: Men receiving delayed ADT for development of metastasis after RP may have a prolonged survival time (13 yrs post RP - range 2–18). Optimizing the time for ADT in these patients requires well-designed, prospective randomized studies. Our data may facilitate the selection of patients and thresholds for implementation of ADT. No significant financial relationships to disclose.

Information regarding postdiagnostic dairy intake and prostate cancer survival is limited. We evaluated intake of total, high-fat and low-fat dairy after prostate cancer diagnosis in relation to disease-specific and total mortality. We included 926 men from the Physicians' Health Study diagnosed with non-metastatic prostate cancer between 1982 and 2000 who completed a diet questionnaire a median of 5 years after diagnosis and were followed thereafter for a median of 10 years to assess mortality. Cox proportional hazards regression was used to estimate associations between dairy intake and prostate cancer specific and all-cause mortality. During 8,903 person-years of follow-up, 333 men died, 56 due to prostate cancer. Men consuming ≥3 servings/day of total dairy products had a 76% higher risk of total mortality and a 141% higher risk of prostate cancer-specific mortality compared to men who consumed less than 1 dairy product/day (hazard ratio (HR) = 1.76, 95% confidence interval (CI): 1.21, 2.55, ptrend < 0.001 for total mortality; HR = 2.41, 95% CI: 0.96, 6.02, ptrend = 0.04 for prostate cancer-specific mortality). The association between high-fat dairy and mortality risk appeared to be stronger than that of low-fat dairy, but the difference between them was not statistically significant (p for difference = 0.57 for prostate cancer-specific mortality and 0.56 for total mortality). Among men without metastases when diagnosed, higher intake of dairy foods after prostate cancer diagnosis may be associated with increased prostate cancer-specific and all-cause mortality.

The Prostate Cancer Intervention Versus Observation Trial: A Randomized Trial Comparing Radical Prostatectomy Versus Expectant Management for the Treatment of Clinically Localized Prostate Cancer

Proton pump inhibitors (PPIs) are commonly prescribed medications that have been shown to have contradicting effects on cancer. We aimed to investigate the effect of pantoprazole and other PPIs on prostate cancer (PCa) specific mortality (PCSM), use of androgen deprivation therapy (ADT), and PCa diagnosis using a large Canadian population-based cohort. We identified 21,512 men aged ≥ 66, with a history of a single negative prostate biopsy and no previous use of any of the analyzed medications between 1994 and 2016. Multivariable Cox regression models with time-dependent covariates were used to assess the associations of PPIs with PCa outcomes. All models included other medications with a putative chemopreventative effect on PCa-outcomes, and were adjusted for age, rurality, comorbidity, and study inclusion year. Over a mean follow-up of 8.06 years (SD 5.44 years), 10,999 patients (51.1%) used a PPI, 5187 patients (24.1%) had PCa, 2043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from PCa. For every 6 months of cumulative use, pantoprazole was associated with a 3.0% (95% CI 0.3-6.0%) increased rate of ADT use, while any use of other PPIs was associated with a 39.0% (95% CI 18.0-64.0%) increased risk of PCSM. No association was found with PCa diagnosis. Upon validation of the potentially negative association of PPIs with PCa, PPI use may need to be reassessed in PCa patients.

Prostate specific antigen kinetics (PSAK) including prostate specific antigen velocity (PSAV) and PSA doubling time (PSADT) are used as predictors of prostate cancer (PCa) therapeutic outcome, disease prognosis, and cancer-specific mortality. However controversy persists regarding use of these parameters in cancer detection. Our aim is to evaluate PSAV as a predictor of PCa and intermediate/high grade PCa (HGPCa). We included 682 patients that underwent repeat transrectal ultrasound guided biopsy after initial negative biopsy. Univariate and multivariate analyses as well as area under the receiver operating characteristic curve (ROC-AUC) were performed to assess predictive accuracy regarding detection of PCa and intermediate/HGPCa (Gleason score ≥ 7). PCa was detected in 179/682 (26.24%) patients. Our univariate analysis suggested that age, total prostate volume (TPV), atypical small acinar proliferation (ASAP) and PSA indices in the form of PSA at the time of repeat biopsy (PSA2), PSAV, PSA density (PSAD2) and percent free PSA at time of repeat biopsy (%FPSA2) were all predictors of overall PCa and intermediate/HGPCa. Meanwhile, our multivariate model showed that factors associated with overall PCa and intermediate/HGPCa were age, PSAV and TPV. In men pursuing a second biopsy after an initial negative biopsy, PSAV was an independent predictor of overall PCa, intermediate and high grade cancer.

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

Development and Internal Validation of a Prostate Health Index Based Nomogram for Predicting Prostate Cancer at Extended Biopsy

Globally, 1.3 million new cases of prostate cancer (PCa) and 359,000 deaths were reported in 2018. Due to rapid population growth and increasing rates of aging worldwide, the PCa has become the 5th leading cause of death in men. Sex hormone binding globulin (SHBG) presents in both men and women and its expression is often associated with the development of PCa and breast cancers. This study was conducted to assess the diagnostic performance of SHBG expression in predicting PCa. A total of 31 patients with PCa and 14 patients with BPH as a control were involved in this study. The SHBG expression of formalin-fixed paraffin-embedded (FFPE) prostate tissue was examined by the quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Receiver operator characteristic (ROC) curves were produced and the area under the curve (AUC) was calculated to evaluate the diagnostic performance of the SHBG expression in predicting the PCa. The AUC of SHBG expression was 0.868 (95% CI 0.764-0.971; p&lt;0.001) which indicated good diagnostic performance. The cutoff value was 6.731 which corresponded to 80% accuracy, 71% sensitivity, and 100% specificity. In conclusion, SHBG expression in bladder cancer tissues could be a molecular marker in PCa diagnosis. ABSTRACT Secara global terdapat 1,3 juta kasus baru kanker prostat (prostate cancer/PCa) dan 359.000 kematian dilaporkan pada tahun 2018. Karena pertumbuhan populasi yang cepat dan meningkatnya angka usia lanjut di seluruh dunia, PCa telah menjadi penyebab kematian utama ke-5 pada pria. Sex hormone binding globulin (SHBG) terdapat pada pria dan wanita dan ekspresinya sering dikaitkan dengan perkembangan PCa dan kanker payudara. Penelitian ini dilakukan untuk menilai potensi SHBG sebagai penanda molekuler dalam diagnosis PCa. Sebanyak 31 pasien PCa dan 14 pasien BPH sebagai kontrol dilibatkan dalam penelitian ini. Ekspresi SHBG dari jaringan prostat formalin-fixed paraffin-embedded (FFPE) diperiksa dengan the quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Receiver operator characteristic (ROC) dihasilkan dan the area under the curve (AUC) dihitung untuk mengevaluasi kinerja diskriminatif ekspresi SHBG dalam diagnosis PCa. AUC ekspresi SHBG adalah 0,868 (95% CI 0,764-0,971; p&lt;0,001) yang menunjukkan kinerja diskriminatif yang baik. Nilai cutoff adalah 6,731 yang berhubungan dengan akurasi 80%, sensitivitas 71% dan spesifisitas 100%. Kesimpulannya, ekspresi SHBG pada jaringan kanker kandung kemih dapat menjadi penanda molekuler dalam diagnosis PCa