Sandler et al. analyzed the databases of 12 major institutions that treated 1170 Gleason 9/10 patients between 2000 and 2013.
- 299 received external beam radiation therapy (EBRT) boost to the prostate + WPRT
- 435 received EBRT only to the prostate + a small margin around it
- 320 received a brachytherapy boost (BBT) to the prostate + WPRT
- 116 received BBT only to the prostate + a small margin around it
- Patients were matched on age, T stage, PSA, Gleason score, and analyzed by ADT duration
After median follow-up of 5.6 years, 5-year biochemical recurrence-free survival (bRFS) was:
- 88% for BBT+WPRT
- 78% for BBT alone
- 66% for EBRT+WPRT
- 58% for EBRT alone
- WPRT was significantly improved by BBT (Hazard Ratio = 0.5, p=0.02) but not by EBRT (HR=0.8, p=0.4))
- Neither distant metastasis-free survival nor prostate cancer-specific survival were significantly improved by WPRT
In interpreting these findings, patients should discuss the following considerations with their radiation oncologists.
Lack of long-term follow-up
As we have observed before (see this link), it can take 15 or more years until over half of high risk patients have detectable metastases (by bone scan/CT) or have succumbed to prostate cancer. In this study, only 35% of those getting EBRT alone had been diagnosed with distant metastases, and only 23% had died of prostate cancer. The rates for all other groups were smaller. As the data mature, we expect that the now-evident and statistically significant differences in biochemical failure will eventually result in higher rates of metastases and mortality.
Lack of local control with EBRT only
ASCENDE-RT proved that prostate cancer is better controlled in high-risk patients by a brachytherapy boost than by EBRT alone. Local control (of cancer in the prostate) is obviously required because the high grade cancer easily progresses and metastasizes from the prostate.
Lack of regional control with surgery
As we have seen, prostatectomy, even when followed by radiation (see this link) seems to provide inferior cancer control compared to BBT with WPRT. This may be because the salvage radiation dose to the prostate bed (usually only 66-70 Gy) is inadequate compared to the primary radiation dose (see this link).
Inadequate coverage/detection of pelvic lymph nodes
In the present study, patients received WPRT to the standard pelvic lymph nodes. We have seen that this is inadequate to reach the cancerous pelvic lymph nodes in over 40% of patients (see this link). Current methods do not allow us to find most of the cancerous lymph nodes (see this link). While PET scans are not yet FDA-approved for high-risk patients (as they are for recurrent patients), there are a few available in clinical trials.
Inadequate dose to pelvic lymph nodes
The dose to pelvic lymph nodes is often about 45-50 Gy given in 1.8 Gy increments. If it's true that perfect cancer control is achieved only with doses around 80 Gy, this treatment may be inadequate to control some of the larger lymph node metastases. This may be especially true because lymph node metastases are not well-oxygenated (hypoxic). As PET/CTs and PET/MRIs become available for high-risk patients, it may become possible to target known lymph node metastases with higher doses. Another fertile area for investigative research is radiosensitization with hyperthermia (see this link).
In RTOG 0534, late Grade 2 or worse gastrointestinal toxicity occurred in 7% of those receiving WPRT. While this is higher than the 2% experiencing this degree of toxicity with prostate-only EBRT treatment, it is nevertheless at a low level. In a large non-randomized, retrospective study comparing WPRT to prostate-only radiation, Parry et al. found no difference in the 3-year cumulative incidence of gastrointestinal and urinary toxicity among high risk and locally advanced patients.
Because we may never have more reliable data, patients and their radiation oncologists must make this decision based on this study and judgement for the foreseeable future.
note: Thanks to Amar Kishan for allowing me to see the full text.