Brachy boost therapy should be reserved for unfavorable risk patients

The ASCENDE-RT trial showed that oncological outcomes were improved among both intermediate risk and high risk men who were treated with external beam radiation (EBRT) and a brachytherapy boost (LDR-BT) to the prostate and adjuvant androgen deprivation therapy (ADT) (see this link). A new study from the University of Michigan suggests that the benefit in intermediate risk men is exclusively among those who have been diagnosed with unfavorable intermediate risk prostate cancer.

They used the NCCN definitions:

• Favorable intermediate risk: Gleason score 3+4 and PSA< 10 ng/ml and stage T1/T2a and <50% of biopsy cores were positive
• Unfavorable intermediate risk: All other intermediate risk

Abugharib et al. retrospectively reported the outcomes of 579 intermediate risk men treated with either EBRT alone or EBRT+LDR-BT between 1995 and 2012. After a median follow-up of 7.5 years:

• The 10-year biochemical recurrence free survival was 92% for the brachy boost therapy vs. 75% for EBRT alone
• Recurrences were cut in half (hazard ratio= 0.48) by the brachy boost after correcting for known confounders
• The improvement due to the boost was only seen in the "unfavorable intermediate risk" group, but not in the favorable intermediate risk group.
• 10-year distant metastasis-free survival did not differ by risk group.
• 6-year cumulative incidence of grade 3 urinary toxicity was 3.5 times higher among men who received brachy boost therapy.
• Toxicity was transient and resolved completely in 57%, partially in 29%, and persisted in only 1 patient.

We recall that ASCENDE-RT reported nearly identical oncological and toxicity outcomes:

• Among those with intermediate-risk prostate cancer, 9-year bPFS was 94% for the brachy boost cohort vs. 70% for EBRT-only.
• Late term Grade 3 GU toxicity reached 19% for the brachy-boost group vs. 5% for the EBRT-only group (3.8 times higher).

Although this was not a randomized clinical trial like ASCENDE-RT, the similarity helps lend credence to their study.

There was a randomized clinical trial RTOG 0232 (see this link) that also showed no benefit to the brachy boost among favorable intermediate risk men.

While ten years is not long enough to evaluate differential effects on metastases and mortality, we may infer from the large difference in the 10-year failure rate that those differences will probably eventuate in more metastases and deaths later on.

It appears that men with unfavorable intermediate risk prostate cancer may benefit from brachy boost therapy. However, men with favorable intermediate risk prostate cancer are at risk of much greater long-term urinary toxicity with no oncological benefit whatever. We can reasonably infer that men with low risk prostate cancer, who may be safely watched with active surveillance, would derive no benefit and only greater toxicity from the combination therapy. Unfortunately some clinics, notably the Radiotherapy Clinics of Georgia, infamously treat even low risk patients with brachy boost therapy (which they market as ProstRCision).