Prognostic value of testosterone castration levels following androgen deprivation and high-dose radiotherapy in localized prostate cancer: Results from a phase III trial.

BACKGROUND/OBJECTIVE: The optimal prognostic value of testosterone following androgen deprivation therapy (ADT) is controversial. We studied the effect of serum testosterone levels on clinical outcome in localized prostate cancer (PCa) treated with ADT and high-dose radiotherapy (HRT). PATIENTS AND METHODS: The DART01/05 trial randomized 355 men with intermediate and high-risk PCa to 4 months of ADT plus HRT (STADT, N = 178) or the same treatment followed by 24 months of ADT (LTADT, N = 177). This study included patients treated with LTADT who had at least 3 determinations of testosterone during ADT (N = 154). Patients were stratified into 3 subgroups by testosterone level: minimum <20 ng/dL; median 20-49 ng/dL; and maximum ≥50 ng/dL. Kaplan-Meyer and Cox regression analysis were used for overall survival (OS) and Fine & Gray regression model for metastasis free survival (MFS), biochemical disease-free survival (bDFS) and time to TT recovery. RESULTS: There were no statistically significant differences in 10-year bDFS, MFS, or OS between the <20 ng/mL and 20-49 ng/dL subgroups. Multivariate analysis showed that a median testosterone ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95%CI 1.28-33.76, p = 0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups. CONCLUSIONS: Our results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20-49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.

Impact of non-adherence to radiotherapy on 1-year survival in cancer patients in Catalonia, Spain.

BACKGROUND: This study aims to assess the effects of non-adherence to external beam radiation therapy in cancer patients receiving treatment with a curative. METHODS: This retrospective cohort study collected health records data for all cancer patients treated with external beam radiotherapy with curative intent in 2016 in Catalonia, Spain. Adherence was defined as having received at least 90% of the total dose prescribed. A logistic regression model was used to assess factors related to non-adherence, and its association with one-year survival was evaluated using Cox regression. RESULTS: The final sample included 8721 patients (mean age 63.6 years): breast cancer was the most common tumour site (38.1%), followed by prostate and colon/rectum. Treatment interruptions prolonged the total duration of therapy in 70.7% of the patients, and 1.0% were non-adherent. Non-adherence was associated with advanced age, female gender, and some localization of primary tumour (head and neck, urinary bladder, and haematological cancers). The risk of death in non-adherent patients was higher than in adherent patients (hazard ratio [HR] 1.63, 95% confidence interval 0.97-2.74), after adjusting for the potential confounding effect of age, gender, tumour site and comorbidity. CONCLUSION: Non-adherence to radiotherapy, as measured by the received dose, is very low in our setting, and it may have an impact on one-year survival.

Is adjuvant radiotherapy needed after curative resection of extrahepatic biliary tract cancers? A systematic review with a meta-analysis of observational studies.

BACKGROUND: The role for adjuvant radiotherapy (ART) after curative resection in extrahepatic cholangiocarcinoma remains unclear. Due to the lack of randomized trials, available data comes from single center experiences or data-based population studies with inconclusive results. OBJECTIVE: To assess the impact of radiotherapy (with or without concurrent chemotherapy) on toxicity and survival of radically resected patients with extrahepatic bile duct cancer (extrahepatic cholangiocarcinoma, gallbladder cancer and pure ampullary cancer). DATA SOURCES AND STUDY SELECTION: Eligible studies with data on survival, recurrence and toxicity were retrieved from the MEDLINE, ISI web of science, EMBASE and Cochrane databases from January 1995 to December 2008, to ensure that all ART treatments were performed with conventional 3D techniques. In the absence of randomized controlled-studies, all observational cohort studies (longitudinal and historical) were initially considered. Ten retrospective cohort studies (where the use of concurrent CT was reported only in 2), met all inclusion criteria and were enrolled for final meta-analysis. Hazard ratio (HR) had to be extracted from survival curves using the Tierney et al. methods. MIX 1.7 statistical software was used for meta-analysis. RESULTS: All studies on ART used conventional 3D-techniques. Patients in the ART cohorts were more likely to have involved surgical margins and positive lymph nodes. For extrahepatic cholangiocarcinoma location, ART significantly improved overall survival (HR 0.62; 95% CI 0.48 to 0.78, p<0.001). Meta-analysis was not feasible for gallbladder cancer and ampullary cancer locations. Late radiation-induced toxicity was low (2-9% late obstruction or GI bleeding). CONCLUSION: In the absence of randomized controlled studies, we found in the present systematic review and meta-analysis of observational studies that, patients with extrahepatic cholangiocarcinoma treated with adjuvant RT have a significant lower risk of dying compared to patients treated with surgery alone.

Phase II study of vinorelbine and estramustine in combination with conformational radiotherapy for patients with high-risk prostate cancer.

PURPOSE: To evaluate the efficacy and safety profile of vinorelbine and estramustine in combination with three-dimensional conformational radiotherapy (3D-CRT) in patients with localized high-risk prostate cancer. METHODS AND MATERIALS: Fifty patients received estramustine, 600 mg/m(2) daily, and vinorelbine, 25 mg/m(2), on days 1 and 8 of a 21-day cycle for three cycles in combination with 8 weeks of 3D-CRT (total dose of 70.2 gray [Gy] at 1.8-Gy fractions or 70 Gy at 2.0-Gy fractions). Additionally, patients received luteinizing hormone-releasing hormone analogs for 3 years. RESULTS: All patients were evaluated for response and toxicity. Progression-free survival at 5 years was 72% (95% confidence interval [CI]: 52-86). All patients who relapsed had only biochemical relapse. The most frequent severe toxicities were cystitis (16% of patients), leucopenia (10% of patients), diarrhea (10% of patients), neutropenia (8% of patients), and proctitis (8% of patients). Six patients (12%) did not complete study treatment due to the patient's decision (n = 1) and to adverse events such as hepatotoxicity, proctitis, paralytic ileus, and acute myocardial infarction. CONCLUSIONS: Vinorelbine and estramustine in combination with 3D-CRT is a safe and effective regimen for patients with localized high-risk prostate cancer. A randomized trial is needed to determine whether the results of this regimen are an improvement over the results obtained with radiotherapy and androgen ablation.