For very high-risk patients, EBRT + BT is superior to surgery or EBRT only (Redux)

In August, Kishan et al. showed a preliminary analysis of oncological outcomes among Gleason score 9 and 10 patients treated with brachy boost therapy (EBRT+BT), external beam radiation therapy alone (EBRT) or surgery (see this link). Because of the limited sample size, some of the differences were not large enough to be statistically significant. Kishan et al. have now expanded their analysis to include 1,001 patients treated between 2000 and 2013, who were treated at several of the top institutions in the US: UCLA, Fox Chase, Cleveland Clinic, Mt. Sinai, and Wheeling Hospital. So far, only an abstract of the study has been presented at the GU Conference. The patient characteristics were as follows: 

• 324 were treated with radical prostatectomy (RP).
• 347 were treated with EBRT only.
• 330 were treated with EBRT + BT (BT was either low dose rate or high dose rate).
• All patients were Gleason 9 or 10 on biopsy.

Treatment specs

• Among the RP patients, 40% had adjuvant or salvage radiation therapy (68 Gy).
• Among radiation patients, 90% had adjuvant ADT
• Median dose of EBRT was 78 Gy.
• adjuvant ADT continued for 18 months, median.
• Median equivalent dose of EBRT+BT was 90 Gy
• adjuvant ADT continued for 12 months.

Oncological outcomes

After a median follow-up of 4.8, 6.4 and 5.1 years for EBRT, EBRT+BT and RP, respectively, the oncological outcomes were as follows:

• The 10-year rates of distant metastases were
  • 39.9% for RP 
  • 34.2% for EBRT
  • 19.7% for EBRT + BT
  • Differences between EBRT + BT and the two others were statistically significant.
• The 10-year rates of prostate cancer-specific mortality (PCSM) were
  • 20.3% for RP
  • 25.2% for EBRT
  • 14.1% for EBRT + BT
  • Differences between EBRT + BT and the two others were statistically significant.

The authors conclude:

Extremely dose-escalated radiotherapy offered improved systemic control and reduced PCSM when compared with either EBRT or RP. Notably, this was achieved despite a significantly shorter median duration of ADT than in the EBRT arm. 

Prostate cancer-specific mortality rates were cut in half by combining EBRT with a BT boost. While this does not prove causality (only a randomized clinical trial can do that) it is highly suggestive that escalated dose can provide lasting cures. There may be good reasons why some high risk patients may have to forgo brachy boost therapy in favor of high dose EBRT or RP with adjuvant EBRT, but for most, brachy boost therapy with ADT will probably be the best choice.

Sadly, a recent analysis of the National Cancer Database showed that utilization of brachy boost therapy for high risk patients has declined precipitously from 28% in 2004 to 11% in 2013. If a patient sees anyone other than the first urologist, he often only sees a single radiation oncologist who only informs him about IMRT. In most parts of the US, there is a dearth of experienced brachytherapists.