Overall, SBRT did not result in any severe acute toxicity (grade 3 or 4) except for grade 3 urinary obstruction in one patient (PO-SBRT). Patients treated with pelvic radiotherapy reported significantly higher grade 2 acute gastrointestinal toxicity (PO-SBRT 15% vs WP-SBRT 29%, p=0.008) but statistically similar acute urinary toxicity (PO-SBRT 26% vs WP-SBRT 36%, p=0.1). Higher acute gastrointestinal toxicity did not persist over time. This was somewhat expected with WP-SBRT given the higher bowel in the irradiated field, despite using strict planning constraints and daily image guidance. This increase in acute GI toxicity did not result in increased late grade 2 rates between the two groups (PO-SBRT 13% vs WP-SBRT 19%, p=0.1). However, cumulative grade 2 urinary toxicity was nearly twice as high with pelvic radiotherapy (46% vs 25%, p=0.003). Overall, severe toxicity was very low (urinary 2.5%, gastrointestinal 1%). Urinary frequency, dysuria, proctitis, and diarrhea were the most frequently reported symptoms. Apart from pelvic radiotherapy, toxicity rates were not influenced by age, stage, or prior TURP. Of note, the toxicity rates observed in our study are similar to the pooled data of 25Gy WP-SBRT from four prospective phase II trials across Canada.2 They reported 48% acute grade 2 urinary toxicity and 41% late grade 2 late urinary toxicity with WP-SBRT, with <3% grade 3-4 toxicity. To summarise, pelvic SBRT resulted in <3% grade 3 toxicity but nearly doubled the grade 2 acute gastrointestinal and late urinary toxicity as compared to prostate-only SBRT. These symptoms were manageable with oral medications without invasive interventions.
Further work is in progress to explore the dosimetric correlates contributing to increased toxicity with pelvic RT. It is hypothesised that the mid to lower doses received by larger volumes of the urinary bladder during WPRT contribute to the increased grade 2 toxicity (Figure 1).3 It is important to note that these are cumulative toxicity rates, which do not capture the actual burden of toxicities over long term follow-up and do not distinguish between temporary and persistent symptoms. Serial evaluation of toxicities and patient-reported quality of life scores, as in randomised trials, estimate the morbidity burden more reliably. Innovative methods such as Month and Severity Score (MOSES) may be able to utilise longitudinal toxicity and QOL assessments more effectively than CTCAE to compare treatment approaches.4 Considering the benefit of pelvic radiotherapy in locally advanced prostate cancer, this study encourages the exploration of pelvic SBRT in RCTs such as the PACE-NODES being planned in the United Kingdom.
Written by: Priyamvada Maitre & Vedang Murthy, Department of Radiation Oncology, Tata Memorial Hospital and Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Homi Bhabha National Institute (HBNI), Mumbai, India
References:
- Murthy V, Adsul K, Maitre P, et al. Acute and late toxicity of prostate-only or pelvic SBRT in prostate cancer: A Comparative Study. International Journal of Radiation Oncology*Biology*Physics 2022; published online June 17. DOI:10.1016/j.ijrobp.2022.05.050.
- Glicksman RM, Liu SK, Cheung P, et al. Elective nodal ultra hypofractionated radiation for prostate cancer: Safety and efficacy from four prospective clinical trials. Radiotherapy and Oncology 2021; 163: 159–64.
- Murthy V, Maitre P, Bhatia J, et al. Late toxicity and quality of life with prostate only or whole pelvic radiation therapy in high risk prostate cancer (POP-RT): A randomised trial. Radiother Oncol 2020; 145: 71–80.
- Ranjan N, Chopra S, Mangaj A, et al. Months and Severity Score (MOSES) in a Phase III trial (PARCER): A new comprehensive method for reporting adverse events in oncology clinical trials. eClinicalMedicine 2022; 47: 101390.