Search

Background: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone‐sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System. Methods: In this observational retrospective cohort study, 400 de novo metastatic hormone‐sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow‐up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan–Meier methods estimated overall survival (OS) and castration‐resistant prostate cancer (CRPC)‐free survival from mHSPC diagnosis date and a log‐rank test compared these outcomes by oligometastatic status. Results: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non‐omHSPC had higher median prostate‐specific antigen at diagnosis (151.7) than omHSPC (44.1). First‐line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non‐omHSPC (14%). More omHSPC patients received metastasis‐directed therapy/prostate radiation therapy (14%) versus non‐omHSPC (2%). Median OS and CRPC‐free survival (in months) were higher in omHSPC versus non‐omHSPC (44.4; 95% confidence interval [CI], 33.9–not estimated vs. 26.2; 95% CI, 20.5–32.5, p =.0089 and 27.6; 95% CI, 22.1–37.2 vs. 15.3; 95% CI, 12.8–17.9, p =.0049), respectively. Conclusions: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non‐omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non‐omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies. In this observational retrospective Veterans Affairs cohort study, 20% of men had de novo oligometastatic hormone‐sensitive prostate cancer (omHSPC). Although first‐line (1L) novel hormonal therapy was similar between groups, 1L chemotherapy use was lower in omHSPC, more omHSPC patients received metastasis‐directed therapy/prostate radiation therapy, and median overall survival and time to castration resistance was longer in men with omHSPC than non‐omHSPC. [ABSTRACT FROM AUTHOR]

High circulating vitamin D levels and supplementation may lower prostate cancer mortality. To probe for direct effects of vitamin D signaling in the primary tumor, we assessed how activation of intratumoral vitamin D signaling in prostate cancer is associated with lethal prostate cancer during long-term follow-up. Among 404 participants with primary prostate cancer in the Health Professionals Follow-up Study and the Physicians' Health Study, we defined a gene score of expected activated intratumoral vitamin D signaling consisting of transcriptionally upregulated (CYP27A1 , CYP2R1 , RXRA , RXRB , and VDR) and downregulated genes (CYP24A1 and DHCR7). We contrasted vitamin D signaling in tumors that progressed to lethal disease (metastases/prostate cancer-specific death, n  = 119) over up to three decades of follow-up with indolent tumors that remained nonmetastatic for >8 years post-diagnosis (n  = 285). The gene score was downregulated in tumor tissue compared with tumor-adjacent histologically normal tissue of the same men. Higher vitamin D gene scores were inversely associated with lethal prostate cancer (odds ratio for highest versus lowest quartile: 0.46, 95% confidence interval: 0.21–0.99) in a dose–response fashion and after adjusting for clinical and pathologic factors. This association appeared strongest among men with high predicted plasma 25-hydroxyvitamin D3 and men with body mass index ≥25 kg/m2. Findings were replicated with broader gene sets. These data support the hypothesis that active intratumoral vitamin D signaling is associated with better prostate cancer outcomes and provide further rationale for testing how vitamin D-related interventions after diagnosis could improve prostate cancer survival through effects on the tumor. [ABSTRACT FROM AUTHOR]

We previously found that higher total 25‐hydroxyvitamin D [25(OH)D] levels were associated with lower risk of lethal prostate cancer. However, the relationships of bioavailable 25(OH)D and vitamin D binding protein (VDBP) with risk of advanced and lethal prostate cancer are unclear. In a prospective case–control study of 156 pairs of advanced prostate cancer cases and controls, we directly measured prediagnostic circulating 25(OH)D and VDBP and calculated bioavailable 25(OH)D using a validated formula. We examined the association of bioavailable 25(OH)D and VDBP levels with risk of advanced and lethal prostate cancer and whether total 25(OH)D levels interacted with VDBP levels to affect the risk. Conditional logistic models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to total 25(OH)D (ptrend = 0.02), bioavailable 25(OH)D levels were not more strongly associated with risk of advanced prostate cancer (ptrend = 0.14). Although VDBP levels were not associated with risk of advanced prostate cancer (ptrend = 0.16), we observed an interaction between total 25(OH)D levels and VDBP levels in relation to risk of advanced prostate cancer (pinteraction = 0.03). Compared to those with total 25(OH)D levels below the median and VDBP levels above the median (at highest risk), men with both levels above the median had a multivariable‐adjusted OR of 0.31 (95% CI, 0.15–0.65) for advanced prostate cancer. We observed similar results when we restricted the analyses to 116 lethal prostate cancer cases and their controls. Our data suggest that VDBP levels may modify the association between total 25(OH)D levels and risk of advanced and lethal prostate cancer. What's new? Higher total circulating 25‐hydroxyvitamin D [25(OH)D] levels have been associated with lower risk of lethal prostate cancer, but the relationships of bioavailable 25(OH)D and vitamin D binding protein (VDBP) with cancer risk remain unclear. In this prospective case–control study, bioavailable 25(OH)D levels were not more strongly associated with advanced prostate cancer risk than total 25(OH)D. There was an interaction between total 25(OH)D and VDBP levels such that men whose levels were high for both total 25(OH)D and VDBP had the lowest risk of advanced and lethal prostate cancer, suggesting that VDBP may modify the association between total 25(OH)D levels and cancer risk. [ABSTRACT FROM AUTHOR]