Prophylactic whole-pelvic radiotherapy improved biochemical failure-free survival and disease-free survival vs prostate-only radiotherapy in patients with high-risk, locally advanced prostate cancer.
Prophylactic whole-pelvic radiotherapy (WPRT) improved biochemical failure-free survival (BFFS) and disease-free survival (DFS) vs prostate-only radiotherapy (PORT) in patients with high-risk, locally advanced prostate cancer, according to data from a phase 3 trial (NCT02302105) published in the Journal of Clinical Oncology.1,2
Among the 224 patients treated on the study, the 5-year BFFS rate was 95.0% (95% CI, 88.4%-97.9%) with WPRT vs 81.2% (95% CI, 71.6%-87.8%) with PORT (unadjusted HR, 0.23; 95% CI, 0.10-0.52; P <.0001). The 5-year DFS rate was also higher with WPRT than PORT, at 89.5% vs 77.2%, respectively (HR, 0.40; 95% CI, 0.22-0.73; P = .002).
However, no statistically significant difference was observed between the 2 arms with regard to 5-year overall survival (OS) rates; with WPRT and PORT, these rates were 92.5% and 90.8%, respectively (HR, 0.92; 95% CI, 0.41-2.05; P = .83).
“Prophylactic WPRT using a contemporary dose and technique along with long-term androgen deprivation therapy [ADT] for high-risk and very high-risk prostate cancer resulted in a large and significantly improved BFFS and DFS as compared with PORT, but did not impact OS,” the study authors wrote. “Until the long-term outcomes of the ongoing trials are reported, prophylactic pelvic radiotherapy should be routinely considered for these patients.”
External beam radiotherapy plus ADT represents the standard recommended radical treatment for patients with nonmetastatic, locally advanced prostate cancer. However, for those without regional pelvic nodal involvement, the benefit of prophylactic treatment with radiotherapy has remained the subject of active debate.
The argument for pelvic radiotherapy is that can eliminate nodal micrometastases, which provides stronger regional control, and thus, possesses the potential to improve survival outcomes. However, 2 large, randomized trials that set out to answer this question have failed to provide conclusive evidence to support the approach.
In the current phase 3 trial, investigators examined PORT or WPRT in patients with high-risk prostate cancer to examine the benefit of treating the pelvic nodes for node-negative, high-risk disease that is undergoing dose-escalated, and moderately hypofractionated, radiation.
To be eligible for enrollment, patients needed to have an estimated risk of pelvic node involvement of at least 20% per the Roach formula. Moreover, patients with clinical stage T1-T3a with Gleason 8-10 and any prostate-specific antigen (PSA), Gleason 7 with PSA of greater than 15 ng/mL, Gleason 6 with PSA of greater than 30 ng/mL, or stage T1-T3a with any Gleason score and any PSA were permitted. Patients needed to have a life expectancy of at least 5 years and be eligible for long-term ADT or surgical castration.
If they had previously received pelvic radiation, had a previous malignancy within 5 years of their present diagnosis, or if they were determined to be ineligible for pelvic radiation, they were excluded from the trial.
A total of 224 patients were enrolled to the trial. Participants were randomized 1:1 to receive either WPRT at a dose of 68 Gy in 25 fractions to the prostate and 50 Gy in 25 fractions to the pelvic nodes (n = 110), or PORT, at a dose of 68 Gy in 25 fractions to the prostate (n = 114). Patients were stratified by Gleason score, type of androgen deprivation, PSA at diagnosis, and previous transurethral resection of the prostate. Additionally, all patients received image-guided, intensity-modulated radiotherapy and at least 2 years of ADT.
The primary end point of the study was BFFS at 5 years, while secondary end points included DFS and OS.
The study participants had a median age of 66 years and a median PSA level of 28.2 ng/mL. More than half of patients had a nodal risk of 40% or less (53.6%) and almost half of patients had a Gleason grade group of 4 or 5. The median estimated Roach nodal risk was 37.8% (interquartile range, 25.1-53.4). Just under half of patients were diagnosed with an advanced tumor stage of T3b or T4. Moreover, 81.1% of patients received medical ADT (81.1) as opposed to surgical ADT (18.9%).
The median follow-up was 68 months and the last patients who had enrolled to the trial completed 3 years of follow-up. Additional data indicated that the 5-year distant metastasis–free survival rate was 95.0% (95% CI, 88.4-97.9) with WPRT vs 87.9% (95% CI, 79.0-93.2) with PORT (HR, 0.35; 95% CI, 0.15-0.82; P = .01).
A multivariable analysis revealed that WPRT and Gleason score demonstrated an association with BFFS that was determined to be statistically significant. Moreover, subgroup analyses indicated that the benefit achieved with WPRT was maintained across all subgroups that had been evaluated for BFFS and DFS. Notably, patients younger than 66 years were observed to experience greater benefit from WPRT in terms of BFFS (P = .03) and DFS (P = .02).
In terms of safety, no statistical significance between acute gastrointestinal and acute genitourinary toxicities were reported between the cohorts. However, significantly more cumulative late, grade 2 or higher genitourinary toxicities were reported in the WPRT cohort vs the PORT cohort, at 20.0% vs 8.9%, respectively (P = .02). No statistically significant difference in grade 2 or higher late gastrointestinal toxicities were reported between the 2 study arms (P = .28).
“An increase in late grade 2 or higher bladder toxicity observed with pelvic radiotherapy could possibly be a result of a larger volume of the bladder being exposed to mid-range dose of 30 to 40 Gy, as detailed previously,” the study authors noted. “Late bowel toxicity, however, was similar between the 2 arms, attributable to the meticulous bowel sparing achieved by the universal use of intensity-modulated radiotherapy.”