Comparative toxicity outcomes of proton‐beam therapy versus intensity‐modulated radiotherapy for prostate cancer in the postoperative setting

Abstract

Background Despite increasing utilization of proton‐beam therapy (PBT) in the postprostatectomy setting, no data exist regarding toxicity outcomes relative to intensity‐modulated radiotherapy (IMRT). The authors compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicity outcomes in patients with prostate cancer (PC) who received treatment with postprostatectomy IMRT versus PBT. Methods With institutional review board approval, patients with PC who received adjuvant or salvage IMRT or PBT (70.2 gray with an endorectal balloon) after prostatectomy from 2009 through 2017 were reviewed. Factors including combined IMRT and PBT and/or concurrent malignancies prompted exclusion. A case‐matched cohort analysis was performed using nearest‐neighbor 3‐to‐1 matching by age and GU/GI disorder history. Logistic and Cox regressions were used to identify univariate and multivariate associations between toxicities and cohort/dosimetric characteristics. Toxicity‐free survival (TFS) was assessed using the Kaplan‐Meier method. Results Three hundred seven men (mean ± SD age, 59.7 ± 6.3 years; IMRT, n = 237; PBT, n = 70) were identified, generating 70 matched pairs. The median follow‐up was 48.6 and 46.1 months for the IMRT and PBT groups, respectively. Although PBT was superior at reducing low‐range (volumes receiving 10% to 40% of the dose, respectively) bladder and rectal doses (all P ≤ .01), treatment modality was not associated with differences in clinician‐reported acute or late GU/GI toxicities (all P ≥ .05). Five‐year grade ≥2 GU and grade ≥1 GI TFS was 61.1% and 73.7% for IMRT, respectively, and 70.7% and 75.3% for PBT, respectively; and 5‐year grade ≥3 GU and GI TFS was >95% for both groups (all P ≥ .05). Conclusions Postprostatectomy PBT minimized low‐range bladder and rectal doses relative to IMRT; however, treatment modality was not associated with clinician‐reported GU/GI toxicities. Future prospective investigation and ongoing follow‐up will determine whether dosimetric differences between IMRT and PBT confer clinically meaningful differences in long‐term outcomes.

Proton beam therapy after radical prostatectomy

“…In the accompanying editorial for our article, Dr. Lee raised several valid points regarding our findings and, more broadly, the use of proton‐beam therapy (PBT) in radiotherapy for prostate cancer (PC) . First, we would like to thank Dr. Lee for taking the time to provide his thoughtful commentary.…”

“…As Dr. Lee mentions, the most recent American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) guidelines regarding postprostatectomy radiotherapy cite a “lack of high‐quality studies” on “novel” treatment modalities and preclude mention of PBT . We agree that our analysis was limited by its retrospective, potentially underpowered nature . However, obtaining prospective, randomized data takes time, resources, and patient participation.…”

“…Noting the above limitations, our analysis used the best feasible statistical measures to account for confounders in the retrospective, nonrandomized setting—providing context for discussing the dosimetric and toxicity profiles of IMRT and PBT within 4 years of follow‐up . As we accumulate data regarding late toxicity and patient‐reported outcomes over time, our analyses, in conjunction with newer data demonstrating reasonable disease control outcomes with PBT, may support the mention of PBT in future guidelines.…”

“…However, the management of toxicities and that of radiation‐associated second malignancies remain incredibly meaningful endpoints to patients, providers, and payers alike, particularly among postprostatectomy patients, who often are younger and expected to survive decades after their diagnosis. Although our analysis did not find differences with regard to acute or initial late toxicity, the median follow‐up was limited . Just as it may appear ambitious to expect large differences with extended follow‐up, given the significant integral dose reduction with PBT, it is likely premature to conclude that no more than a small benefit exists.…”

Proton‐beam therapy after radical prostatectomy: Continued DVH idolatry?

“…In this issue of Cancer , Santos and colleagues have provided a comparative analysis of toxicity between IMRT and PBT after RP in men with PC . They performed a case‐matched cohort analysis using nearest‐neighbor matching and attempted to identify associations between the development of genitourinary (GU) or GI toxicity and patient/dosimetric characteristics.…”