Men With Adverse Pathology at Radical Prostatectomy May Experience Reduction in Risk of Death With Adjuvant Radiation Therapy

For men with prostate cancer who have adverse pathology including positive pelvic lymph nodes (pN1) or prostate Gleason score 8 to10 and disease extending beyond the prostate (pT3/4), adjuvant radiation therapy should be considered due to its potential to significantly reduce the risk of all-cause mortality, according to data published in the Journal of Clinical Oncology.

Results from the trial indicated that after a median follow-up of 8.16 years (interquartile range [IQR], 6.00-12.10 years), 2104 (8.06%), 539 (25.62%) of whom died from prostate cancer. Moreover, compared with early sRT, adjuvant radiation therapy was associated with a significantly lower risk of all-cause mortality for men with adverse pathology at radical prostatectomy when men with pN1 prostate cancer were excluded (HR, 0.31; 95% CI, 0.12-0.78; P = .01) or included (HR, 0.61; 95% CI, 0.41-0.89; P = .01).

“This association of reduced all-cause mortality risk with adjuvant compared with early sRT is strengthened given that men who underwent adjuvant compared with early sRT had less favorable prostate cancer prognostic factor distributions, which should have placed them at higher risk for needing (salvage androgen deprivation therapy; sADT) and dying,” the investigators wrote. “However, they had lower rates of sADT use and a lower all-cause mortality risk.”

While no reduction in progression-free survival (PFS) has been observed with adjuvant radiation therapy compared with early salvage radiation therapy (sRT) following radical prostatectomy, investigators hypothesized that possible benefit may have been overlooked for an underrepresented cohort of men with adverse pathology at radical prostatectomy.

“Three randomized trials and a meta-analysis found no difference in PFS for adjuvant compared with early sRT use,” the authors wrote. “However, a benefit might have been missed in men with adverse pathology at radical prostatectomy because of inadequate power and the presence of immortal time bias.”

The study included 26,118 men with pT2-4N0 or N1M0 prostate cancer who were treated with radical prostatectomy and pelvic lymph node assessment consecutively between June 23, 1989, and July 26, 2016. The cohort of men, who had a median age of 62 years (range, 57-67 years), were then followed for possible treatment with adjuvant or early sRT.

Of the men who were included in the study, 3.14% had underwent adjuvant radiotherapy, which was generally administered within 6 months of radical prostatectomy, and 17.72% received early RT at a median prostate-specific antigen (PSA) level of 0.30 ng/mL (IQR, 0.20-0.62). In total, 14.24% of those in the early sRT group had persistent PSA, defined as 0.1 ng/mL or more postoperatively. Adjuvant and salvage ADT were used in 1.35% and 9.69% of patients, respectively.

Additional findings from the study indicated that among those who received adjuvant therapy vs sRT, including those with pN1 disease, a significantly higher proportion of extra-prostatic extension (pT3a) or higher (97.90% vs 94.48%; P = .002) and margin-positive disease (82.71% vs 45.68%; P< .001) was observed. sADT therapy yielded significantly lower pT3a or higher (36.21% vs 47.53%; P< .001). Notably, men with adverse pathology who received adjuvant radiotherapy vs sRT, excluding pN1 prostate cancer, had a significantly higher proportion of margin-positive disease (88.07% vs 45.17%; P< .001) and decreased use of sADT (35.78% vs 45.84%; P = .06).

“The clinical significance of this finding is that there exists a subset of men with adverse pathology at RP who may experience a lower ACM risk when adjuvant as opposed to early sRT is delivered,” the authors wrote. “Yet, 3 randomized trials and a meta-analysis on the basis of PFS primarily driven by PSA failure suggest no difference when using adjuvant compared with early sRT, which can lead physicians to not offer aRT to any patient, which could result in an increased risk of death in the subset of men with adverse pathology at RP.”

Regardless, some limitations exist with this research, including the potential presence of selection bias in these nonrandomized comparisons. This suggests that some patients undergoing adjuvant radiation therapy could have been healthier than the comparative therapy, leading to longer survival.

Reference

Tilki D, Chen MH, Wu J, et al. Adjuvant versus early salvage radiation therapy for men at high risk for recurrence following radical prostatectomy for prostate cancer and the risk of death. J Clin Oncol. 2021;39(20):2284-2293. doi:10.1200/JCO.20.03714