Sam Regan

Background: Biochemical recurrence (BCR) after radical prostatectomy for localized prostate cancer affects nearly one in four patients. Although androgen deprivation therapy (ADT) is used in this setting, its impact on metastatic disease outcomes remains unclear in contemporary population-based cohorts. Methods: We performed a retrospective cohort study using national Veterans Health Administration electronic health record and Central Cancer Registry data. Men undergoing radical prostatectomy between 2005 and 2015 were followed through 2019. We defined BCR as prostate-specific antigen (PSA) ≥0.20 ng/mL. We examined biochemically recurrent prostate cancer management and disease progression to castration resistance and metastatic disease. Results: Of 28,452 men with prostate cancer treated surgically, 7,912 (28%) developed BCR, with 10.5% developing metastatic disease (median follow-up, 110 months). Salvage ADT with or without radiotherapy was administered to 24% of patients. In adjusted models, salvage ADT use was associated with worse metastasis-free survival [adjusted hazard ratio (aHR), 1.96; 95% confidence interval (CI), 1.71–2.25] and increased castration-resistant therapy (aHR, 20.51; 95% CI, 14.48–29.04). Higher pathologic T stage, Gleason grade group, PSA, nodal involvement, and faster PSA doubling times were predictive of metastasis. Conclusions: In this large national cohort of men with BCR after surgery, most did not develop metastatic disease during nearly 10 years of follow-up, and one in four patients was treated with ADT. The association between ADT and adjusted outcomes likely reflects more aggressive disease among men selected for hormonal therapy. Impact: These findings underscore the importance of continued risk stratification refinement and management optimization for recurrent prostate cancer.

Data Supplement -FDG Calculation Methods

Study representativeness table

Purpose:We conducted a phase II multicenter clinical trial to test the hypothesis that 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)–based chemoradiation (CRT) dose deescalation would provide noninferior locoregional control compared with historical controls among patients with early-stage p16+ oropharyngeal cancer. We also hypothesized that human papillomavirus (HPV) circulating tumor DNA (ctDNA) changes during treatment predict locoregional recurrence (LRR).Patients and Methods:Patients with stage I/II p16+ oropharyngeal squamous cell carcinoma were planned to receive radiation 70 Gy in 35 fractions with concurrent weekly carboplatin and paclitaxel. All patients underwent FDG-PET at baseline and at radiation therapy (RT) fraction 10. Patients with ≥50% decrease from baseline to mid-treatment metabolic tumor volume had treatment deescalated to 54 Gy in 27 fractions. The primary endpoint was LRR. Plasma HPV ctDNA was evaluated weekly and in surveillance.Results:Of 84 evaluable patients, 43% met deescalation criteria. With a median follow-up of 37.8 months, 24-month LRR for the entire cohort was 7.8% [90% confidence interval (CI), 2.6%–12.6%], which was less than the 25% rate specified for assessing noninferiority, thereby meeting the primary endpoint. At 1 month after RT, the mean of multiple quality of life measures between the two groups was improved in the 54 Gy cohort, exceeding the minimal clinically important difference threshold. During CRT, week 1 percentage increase in ctDNA relative to baseline was significantly associated with worse loco-regional control (LRC; HR = 1.052 per 10 percentage point increase in ctDNA; 95% CI, 1.007–1.099; P = 0.023) and loco-regional progression-free survival (HR = 1.038; 95% CI, 1.002–1.076; P = 0.035).Conclusions:FDG-PET–based RT dose personalization resulted in promising LRR outcomes in early-stage oropharynx cancer with improved short-term patient-reported outcomes. Furthermore, HPV ctDNA changes early in treatment may predict LRC.