Howard, Lauren E

Abstract Bone pain is a well-known quality-of-life detriment for individuals with prostate cancer and is associated with survival. This study expands previous work into racial differences in multiple patient-reported dimensions of pain and the association between baseline and longitudinal pain and mortality. This is a prospective cohort study of individuals with newly diagnosed advanced prostate cancer enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) from 2017 to 2023 at U.S. sites. Differences in four pain scores at study enrollment by race were investigated. Cox proportional hazards models and joint longitudinal survival models were fit for each of the scale scores to estimate HRs and 95% confidence intervals (CI) for the association with all-cause mortality. The cohort included 879 individuals (20% self-identifying as Black) enrolled at 38 U.S. sites. Black participants had worse pain at baseline compared with White participants, most notably a higher average pain rating (mean 3.1 vs. 2.2 on a 10-point scale). For each pain scale, higher pain was associated with higher mortality after adjusting for measures of disease burden, particularly for severe bone pain compared with no pain (HR, 2.47; 95% CI: 1.44–4.22). The association between pain and all-cause mortality was stronger for participants with castration-resistant prostate cancer compared with those with metastatic hormone-sensitive prostate cancer and was similar among Black and White participants. Overall, Black participants reported worse pain than White participants, and more severe pain was associated with higher mortality independent of clinical covariates for all pain scales. Significance: Black participants with advanced prostate cancer reported worse pain than White participants, and more pain was associated with worse survival. More holistic clinical assessments of pain in this population are needed to determine the factors upon which to intervene to improve quality of life and survivorship, particularly for Black individuals.

Objective To evaluate biochemical recurrence ( BCR ) patterns amongst men undergoing radical prostatectomy ( RP ) with specimens having negative ( NSM ), positive ( PSM ), and close surgical margins ( CSM ) from the Shared Equal Access Regional Cancer Hospital ( SEARCH ) cohort, as PSM after RP are a significant predictor of biochemical failure and possible disease progression, with CSM representing a diagnostic challenge for surgeons. Patients and Methods Men undergoing RP between 1988 and 2015 with known final pathological margin status were evaluated. The cohort was divided into three groups based on margin status; NSM , PSM , and CSM . CSM were defined by distance of tumour ≤1 mm from the surgical margin. BCR was defined as a prostate‐specific antigen ( PSA ) level of >0.2 ng/mL, two values at 0.2 ng/mL, or secondary treatment for an elevated PSA level. Predictors of BCR , metastases, and mortality were analysed using Cox proportional hazard models. Results Of 5515 men in the SEARCH database, 4337 (79%) men met criteria for inclusion in the analysis. Of these, 2063 (48%) had NSM , 1902 (44%) had PSM , and 372 (8%) had CSM . On multivariable analysis, relative to NSM , men with CSM had a higher risk of BCR (hazard ratio [ HR ] 1.51, 95% confidence interval [ CI ] 1.25–1.82; P < 0.001) but a decreased risk of BCR when compared to those men with PSM ( HR 2.09, 95% CI 1.86–2.36; P < 0.001). Metastases, prostate cancer‐specific mortality and all‐cause mortality did not differ based on margin status alone. Conclusions Management of men with CSM is a diagnostic challenge, with a disease course that is not entirely benign. The evaluation of other known risk factors probably provides greater prognostic value for these men and may ultimately better select those who may benefit from adjuvant therapy.

ObjectiveTo determine if cholesterol is a risk factor for the development of lower urinary tract symptoms in asymptomatic men.MethodsA post‐hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study was carried out in 2323 men with baseline International Prostate Symptom Score <8 and not taking benign prostatic hyperplasia or cholesterol medications. Cox proportion models were used to test the association between cholesterol, high‐density lipoprotein, low‐density lipoprotein and the cholesterol : high‐density lipoprotein ratio with incident lower urinary tract symptoms, defined as first report of medical treatment, surgery or two reports of an International Prostate Symptom Score >14.ResultsA total of 253 men (10.9%) developed incident lower urinary tract symptoms. On crude analysis, higher high‐density lipoprotein was associated with a decreased lower urinary tract symptoms risk (hazard ratio 0.89, P = 0.024), whereas total cholesterol and low‐density lipoprotein showed no association. After multivariable adjustment, the association between high‐density lipoprotein and incident lower urinary tract symptoms remained significant (hazard ratio 0.89, P = 0.044), whereas no association was observed for low‐density lipoprotein (P = 0.611). There was a trend for higher cholesterol to be linked with higher lower urinary tract symptoms risk, though this was not statistically significant (hazard ratio 1.04, P = 0.054). A higher cholesterol : high‐density lipoprotein ratio was associated with increased lower urinary tract symptoms risk on crude (hazard ratio 1.11, P = 0.016) and adjusted models (hazard ratio 1.12, P = 0.012).ConclusionsAmong asymptomatic men participating in the REDUCE study, higher cholesterol was associated with increased incident lower urinary tract symptoms risk, though the association was not significant. A higher cholesterol : high‐density lipoprotein ratio was associated with increased incident lower urinary tract symptoms, whereas higher high‐density lipoprotein was protective. These findings suggest dyslipidemia might play a role in lower urinary tract symptoms progression.

Objectives To test the external validity of a previously developed risk table, designed to predict the probability of a positive bone scan among men with non‐metastatic (M0) castration‐resistant prostate cancer ( CRPC ), in a separate cohort. Patients and Methods We retrospectively analysed 429 bone scans of 281 patients with CRPC , with no known previous metastases, treated at three Veterans Affairs Medical Centers. We assessed the predictors of a positive scan using generalized estimating equations. Area under the curve ( AUC ), calibration plots and decision‐curve analysis were used to assess the performance of our previous model to predict a positive scan in the current data. Results A total of 113 scans (26%) were positive. On multivariable analysis, the only significant predictors of a positive scan were log‐transformed prostate‐specific antigen ( PSA ): hazard ratio ( HR ) 2.13; 95% confidence interval ( CI ) 1.71–2.66 ( P < 0.001) and log‐transformed PSA doubling time ( PSADT ): HR 0.53; 95% CI 0.41–0.68 ( P < 0.001). Among men with a PSA level <5 ng/ mL , the rate of positive scans was 5%. The previously developed risk table had an AUC of 0.735 to predict positive bone scan with excellent calibration, and provided additional net benefit in the decision‐curve analysis. Conclusion We have validated our previously developed table to predict the risk of a positive bone scan among men with M0/Mx CRPC . Use of this risk table may allow better tailoring of patients' scanning to identify metastases early, while minimizing over‐imaging. Regardless of PSADT , positive bone scans were rare in men with a PSA <5 ng/ mL .

Abstract The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other antidiabetic medications, versus no antidiabetic medication use, and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4–6 and high-grade Gleason 7–10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any antidiabetic medications, 141 (26%) reported use of at least one antidiabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR, 1.19; P = 0.50), low- (OR, 1.01; P = 0.96), or high-grade (OR, 1.83; P = 0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin antidiabetic medications and prostate cancer risk in both crude (OR, 1.02; P = 0.95) and multivariable analysis (OR, 0.85; P = 0.56). Furthermore, the interactions between antidiabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all P &gt; 0.05). Among diabetic men with a negative prestudy biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis. Cancer Prev Res; 8(11); 1055–60. ©2015 AACR.