Radiation therapy and radical prostatectomy (RP) offer men with Gleason score 9–10 prostate cancer (PCa) equivalent cancer-specific and overall survival, according to a new study. Findings also suggest that extremely dose-escalated radiation therapy plus androgen deprivation therapy (ADT) might be the optimal upfront treatment for these patients, researchers concluded in a paper published online ahead of print in European Urology. The investigators noted that their study is the largest comparative study of outcomes exclusively for patients with Gleason score 9–10 PCa. The study, led by Amar U. Kishan, MD, of the University of California Los Angeles, included 487 patients with biopsy Gleason 9–10 disease. Of these, 230 underwent external beam radiation therapy (EBRT), 87 were treated with EBRT and brachytherapy (BT), and 170 underwent RP. Most radiation therapy patients received androgen deprivation therapy and dose-escalated radiation therapy. The median follow-up was 4.6 years. Local salvage and systemic salvage were performed more frequently among RP patients (49% vs. 30.1%) when compared with EBRT patients (0.9% and 19.7%) or EBRT plus BT patients (1.2% and 16.1%), Dr. Kishan's group reported. The 5- and 10-year rates of cancer-specific and overall survival were similar across the 3 cohorts after adjusting for age, clinical stage, biopsy Gleason score, initial PSA level, year of treatment, and use of salvage therapies, according to the investigators. For example, the 10-year rates of cancer-specific mortality were 8.4%, 4.4%, and 8.3% in the EBRT, EBRT + BT, and RP groups, respectively. The 10-year rates of overall survival were 79.9%, 84.7%, and 90.3%, respectively. The 5-year and 10-year distant metastasis-free survival rates were significantly higher with EBRT plus BT (94.6% and 89.8%) than with EBRT (78.7% and 66.7%) or RP (79.1% and 61.5%). “Our finding that EBRT + BT provides improved systemic control over both EBRT and RP in this setting is novel, and suggests that optimal local control (offered by extreme dose-escalation) and an upfront method of systemic control (offered by a frequent use of ADT in this cohort) may represent the best upfront treatment strategy for these patients who are at high risk of harboring micrometastatic disease at presentation,” the investigators wrote. The equivalence of cancer-specific and overall survival following EBRT-based treatments and RP in the current study differs from most prior comparative studies, the investigators pointed out. “Importantly, the majority of EBRT patients in prior studies received neither long-course ADT nor high-dose RT,” they wrote. “In contrast, the majority of RT patients treated in our series were treated in accordance with contemporary standards.” They noted that nearly 94% of EBRT patients had upfront ADT with a median duration of 24 months and 97% of EBRT patients received doses isoeffective to, or higher than, 75.6 Gy in 1.8-Gy fractions.
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Men with higher selenium levels may be at lower risk of aggressive prostate cancer (PCa), according to a new study. Each 80th percentile increase in blood and nail selenium concentrations was associated with a significant 57% and 82% decreased odds of aggressive PCa, respectively, after adjusting for body mass index, age, height, smoking status, education, and marital status, Naomi E. Allen, MSc, DPhil, of the University of Oxford in Oxford, UK, and colleagues reported in the Journal of the National Cancer Institute (2016;108:djw153). The researchers defined aggressive PCa as advanced stage disease and/or PCa-related death. The concentration of selenium in nail, but not blood, was inversely associated with the risk of total PCa. Each 80th percentile increase in nail selenium associated with a significant 71% decreased odds of total PCa and 67% decreased odds of non-aggressive PCa. “Because a substantial proportion of PSA-detected cancers remain biologically indolent for many years, the identification of factors that are associated with the development of clinically aggressive cancers is important,” Dr Allen's group wrote. “Hence, our finding that both blood and nail concentrations were associated with a lower risk of aggressive prostate cancer is of potential etiological relevance.” The results are based on an analysis of individual participant data from 15 prospective studies in which data were available for 4,527 case patients and 6021 control patients for blood selenium and 1970 cases and 2086 controls for nail selenium. The researchers acknowledged that it is possible that the inverse association of blood and nail selenium level and risk of aggressive PCa might be due to confounders, but noted that they adjusted their analyses for a range of lifestyle factors as well as the matching factors used in the individual studies, “none of which materially influenced the risk estimates.” Dr Allen and her collaborators pointed out that nails are a more reliable marker of long-term selenium exposure, and this might explain why nail, and not blood, selenium levels are inversely associated with the risk of total PCa. Nail clippings provide a measure of exposure over several weeks and up to 12 months prior to sample collection, they noted. Blood levels reflect shorter-term (1–2 weeks) selenium exposure. According to the researchers, the absence of an association between blood selenium levels and total PCa risk is consistent with the findings of the Selenium and Vitamin E Cancer Prevention Trial (SELECT). In this phase 3 trial, investigators randomly assigned 35,533 men to 1 of 4 groups: placebo plus placebo; vitamin E plus placebo; selenium plus placebo; and selenium plus vitamin E. The median follow-up was 5.5 years. Selenium was dosed at 200 µg/day and vitamin E was dosed at 400 IU/day. Selenium or vitamin E, alone or in combination, did not significantly affect PCa risk. |
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