ABSTRACT
BACKGROUND: Most men diagnosed with prostate cancer today have organ-confined disease and low risk of disease recurrence after radical prostatectomy. Testosterone deficiency in prostate cancer survivors contributes to impaired health-related quality of life but testosterone treatment is viewed as a contraindication in this population. OBJECTIVES: We describe the design of the first randomized trial to determine the safety and efficacy of testosterone treatment in men who have undergone prostatectomy for non-aggressive prostate cancer and have symptomatic testosterone deficiency. METHODS: Surviving Prostate cancer while Improving quality of life through Rehabilitation with Testosterone Trial is a randomized, placebo-controlled, double-blind, parallel group trial in 142 men, ≥ 40 years, who have undergone radical prostatectomy for organ-confined prostate cancer, Gleason score ≤ 7 (3+4), Stage pT2, N0, M0 lesions and have symptomatic testosterone deficiency and undetectable prostate specific antigen for > 2 years after surgery. Eligible participants are randomized to weekly intramuscular injections of 100-mg testosterone cypionate or placebo for 12 weeks and followed for another 12 weeks. Primary endpoint is change from baseline in sexual activity. Secondary outcomes include change in sexual desire, erectile function, energy, lean and fat mass, physical and cognitive performance. Safety is assessed by monitoring prostate-specific antigen, lower urinary tract symptoms, hemoglobin, and adverse events. RESULTS: The trial is being conducted at two trial sites in Boston, MA and Baltimore, MD. As of July 30, 2022, 42 participants have been randomized. No prostate-specific antigen or clinical recurrence has been noted to-date. DISCUSSION: Recruitment was slowed by coronavirus disease 2019-related closures, slow subsequent ramp-up of research activities, and patient concerns about safety of testosterone treatment. Despite these challenges, participant retention has been high. CONCLUSION: The Surviving Prostate cancer while Improving quality of life through Rehabilitation with Testosterone Trial, a placebo-controlled, randomized trial, will determine whether testosterone replacement therapy is safe and efficacious in correcting symptoms of testosterone deficiency in prostate cancer survivors, and potentially inform clinical practice.
ABSTRACT
Importance: Resource limitations because of pandemic or other stresses on infrastructure necessitate the triage of time-sensitive care, including cancer treatments. Optimal time to treatment is underexplored, so recommendations for which cancer treatments can be deferred are often based on expert opinion. Objective: To evaluate the association between increased time to definitive therapy and mortality as a function of cancer type and stage for the 4 most prevalent cancers in the US. Design, Setting, and Participants: This cohort study assessed treatment and outcome information from patients with nonmetastatic breast, prostate, non-small cell lung (NSCLC), and colon cancers from 2004 to 2015, with data analyzed January to March 2020. Data on outcomes associated with appropriate curative-intent surgical, radiation, or medical therapy were gathered from the National Cancer Database. Exposures: Time-to-treatment initiation (TTI), the interval between diagnosis and therapy, using intervals of 8 to 60, 61 to 120, 121 to 180, and greater than 180 days. Main Outcomes and Measures: 5-year and 10-year predicted all-cause mortality. Results: This study included 2â¯241â¯706 patients (mean [SD] age 63 [11.9] years, 1â¯268â¯794 [56.6%] women, 1â¯880â¯317 [83.9%] White): 1â¯165â¯585 (52.0%) with breast cancer, 853â¯030 (38.1%) with prostate cancer, 130â¯597 (5.8%) with NSCLC, and 92â¯494 (4.1%) with colon cancer. Median (interquartile range) TTI by cancer was 32 (21-48) days for breast, 79 (55-117) days for prostate, 41 (27-62) days for NSCLC, and 26 (16-40) days for colon. Across all cancers, a general increase in the 5-year and 10-year predicted mortality was associated with increasing TTI. The most pronounced mortality association was for colon cancer (eg, 5 y predicted mortality, stage III: TTI 61-120 d, 38.9% vs. 181-365 d, 47.8%), followed by stage I NSCLC (5 y predicted mortality: TTI 61-120 d, 47.4% vs 181-365 d, 47.6%), while survival for prostate cancer was least associated (eg, 5 y predicted mortality, high risk: TTI 61-120 d, 12.8% vs 181-365 d, 14.1%), followed by breast cancer (eg, 5 y predicted mortality, stage I: TTI 61-120 d, 11.0% vs. 181-365 d, 15.2%). A nonsignificant difference in treatment delays and worsened survival was observed for stage II lung cancer patients-who had the highest all-cause mortality for any TTI regardless of treatment timing. Conclusions and Relevance: In this cohort study, for all studied cancers there was evidence that shorter TTI was associated with lower mortality, suggesting an indirect association between treatment deferral and mortality that may not become evident for years. In contrast to current pandemic-related guidelines, these findings support more timely definitive treatment for intermediate-risk and high-risk prostate cancer.