Updated results of high-dose rate brachytherapy and external beam radiotherapy for locally and locally advanced prostate cancer using the RTOG-ASTRO phoenix definition

PURPOSE: To evaluate the prognostic factors for patients with local or locally advanced prostate cancer treated with external beam radiotherapy (RT) and high dose rate brachytherapy (HDR) according to the RTOG-ASTRO Phoenix Consensus Conference. MATERIALS AND METHODS: The charts of 209 patients treated between 1997 and 2005 with localized RT and HDR as a boost at the Department of Radiation Oncology, AC Camargo Hospital, Sao Paulo, Brazil were reviewed. Clinical and treatment parameters i.e.: patient's age, Gleason score, clinical stage, initial PSA (iPSA), risk group (RG) for biochemical failure, doses of RT and HDR were evaluated. Median age and median follow-up time were 68 and 5.3 years, respectively. Median RT and HDR doses were 45 Gy and 20 Gy. RESULTS: Disease specific survival (DSS) at 3.3 year was 94.2%. Regarding RG, for the LR (low risk), IR (intermediate risk) and HR (high risk), the DSS rates at 3.3 years were 91.5%, 90.2% and 88.5%, respectively. On univariate analysis prognostic factors related to DSS were RG (p = 0.040), Gleason score &#8804; 6 ng/mL (p = 0.002), total dose of HDR &#8805; 20 Gy (p < 0.001) On multivariate analysis the only statistical significant predictive factor for biochemical control (bNED) was the RG, p < 0.001 (CI - 1.147-3.561). CONCLUSIONS: Although the radiation dose administered to the prostate is an important factor related to bNED, this could not be established with statistical significance in this group of patients. To date , in our own experience, HDR associated to RT could be considered a successful approach in the treatment of prostate cancer

Mechanisms of acquired resistance to androgen receptor targeting drugs in castration-resistant prostate cancer

After initial response to androgen receptor targeting drugs abiraterone or enzalutamide, most patients develop progressive disease and therefore, castration resistant prostate cancer (CRPC) remains a terminal disease. Multiple mechanisms underlying acquired resistance have been postulated. Intratumoral androgen synthesis may resume after abiraterone treatment. A point mutation in the ligand binding domain of androgen receptor may confer resistance to enzalutamide. Emergence of androgen receptor splice variants lacking the ligand binding domain may mediate resistance to abiraterone and enzalutamide. Steroid receptors such as glucocorticoid receptor may substitute for androgen receptor. Drugs with novel mechanisms of action or combination therapy, along with biomarkers for patient selection, may be needed to improve the therapy of CRPC