Are we ready to use hypofractionated instead of conventional radiotherapy for prostate cancer? Not yet

Abstract

Prostate cancer is still the most frequently diagnosed cancer in American men despite a 7.6% decrease in cancer incidence between 2011 and 2014 (1). In Brazil, about 68,220 men are expected to be diagnosed with prostate cancer in 2018 (2). Recently, a consensus on the use and indications of Hypofractionated Radiation Therapy (hRT) or Ultrahypofractionation radiotherapy, also referred to “extreme hypofractionation”, “stereotactic ablative body radiation therapy” and “stereotactic body radiation therapy” (SBRT) for Localized Prostate Cancer (PCa) from the ASTRO, ASCO, and AUA were published (3-5). This consensus was based on key questions that addressed the indications of the different schedules of hypofractionation for the different risk groups of PCa when compared to conventionally fractioned external beam radiotherapy (EBRT), using daily fractions of 180-200 cGy given in 7 to 8 weeks, for doses up to 7,800 cGy. Several studies have already provided evidence for the efficacy of dose-escalation on biochemical control (BC) of PCa and results from randomized trials (RCTs) have shown a direct relation between increasing the radiation dose given to the prostate and/or seminal vesicles and BC (6-9); however, randomized data comparing different methods of dose escalation are sparse (10). Unfortunately the consensus on the use of hRT did not include forms of hypofractionation that combine different techniques of radiation like EBRT associated to brachytherapy, using either high or low dose rate sources. The role of high dose rate (HDR) brachytherapy in the treatment of men with PCa is not well defined, but the results of the trials mentioned above have shown that escalated doses are superior to conventional doses to achieve BC in all risk groups of PCa. HDR brachyteharpy can escalate the dose given to the prostate by the combination with EBRT and has also the potential biological advantage through the delivery of doses in higher levels than the ones evaluated in the published consensus (11). Mature data published have already evaluated the 10-year outcomes of intermediateand high-risk patients noting a clear dose response by increasing the dose escalation through HDR doses (12). The results of the first randomized prospective trial addressing dose escalation using an HDR and EBRT were published in 2012, noting 18% increase in the disease specific survival for patients who had combined modality treatments (p = 0.04), reflecting a 31% reduction in the risk of recurrence (p = 0.01) and no evidence of an increase in long-term severe morbidity (13). Moderate hRT was defined in that guideline as treatments given with fractions size between 240 cGy and 340 cGy per day, three to five times a week over 3.8 to 5.6 weeks. SBRT was defined as EBRT administered with fractions size of more than 500 cGy independent of considerations of technique used. The literature has four large prospective RCTs and additional single institution RCTs demonstrating Vol. 45 (1): 5-9, January February, 2019