Discussion
toxicity, toxicities, genitourinary toxicity, sexual dysfunction, tumors, urinary and bowel symptoms
RECURRENCES, DISEASE, PROSTATE, TUMORS, URETHRA
Several prospective trials, notably the HYPO-RT-PC Phase 3 randomized trial (ISRCTN 45905321) and early results on toxicity and QofL from the PACE-B study (NCT01584258), have established SBRT as a standard-of-care treatment option for patients with localized PCa. Previous pivotal trials of dose escalation to the whole prostate with 45 Gy and 47.5 Gy have shown no evidence of severe toxicity.Concerning genitourinary toxicity, we found Grade 1 and 2 acute toxicity in 57.5% and 15% of the patients, respectively. Reported rates of acute Grade 1 or 2 GU toxicity in previous SBRT trials that limited the dose to 35–36.25 Gy were between 28 and 78%.In our trial, Grade 1 and 2 late GU toxicities was 66.6 and 12.1%, respectively. The landmark HYPO-RT-PC randomized trialOur study found that acute Grade 1 and 2 GI toxicity occurred in 24.2 and 6.1% of patients, respectively. Previous SBRT trials that irradiated the whole prostate gland with a dose of 35 to 40 Gy found acute Grade 1 to 2 GI toxicity rates ranging from 16 to 82%.In our study, patient-reported outcomes and clinician-reported assessments were performed with the aim of being complementary and to more fully document the burden of toxicities and subjective symptoms, such as sexual dysfunction. We observed minimal declines in PR25 urinary and bowel symptoms score as well as IPSS score.The HYPO-RT-PC trial recently reported the results of QofL comparisons between ultra-hypofractionated and conventional fractionated-RT, demonstrating that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after treatment completion.Our study QofL analysis truly reflected physicians reported outcome and are in line with that previously reported in the literature.It’s tempting to look at clinical outcomes in our trial, especially since we included a significant proportion of high-risk patients and ADT was omitted in all of them. However, since our study was not powered to assess clinical effectiveness, any interpretation of the biochemical relapse-free survival outcome should be done with caution. We observed PSA relapses in 30% of the patients at a median of 61 months. Most of the recurrences observed were in patients with high-risk disease. This failure rate is comparable to that reported by Lee et al,Several limitations of our study are acknowledged. The sample size is insufficient to draw firm conclusions. The follow-up period is still insufficient to assess the biochemical or survival outcome. Another limitation is that we decided to exclude patients with IPSS scores greater than 14, tumors near the urethra, or prostate sizes greater than 70 cm3, thus our findings cannot be extended to all patients with intermediate-high risk PCa.