Endometrial Cancer: Vaginal Brachytherapy vs Whole Pelvis

In this weeks JCO, the first results of the PORTEC 2 trial are published.

In this randomized trial, 427 patients >= 60 years of age with IC grade 1 or 2, IB grade 3, or any age and IIA disease (excluding grade 3 with >50% myometrial invasion, were randomized between vaginal brachytherapy (7Gy q week x 3, or 30Gy LDR) and WPRT (46Gy, 2Gy/day). Note the inclusion criteria; this excludes the IC grade 3 risk group which at the time of the trial design were at too high of a risk not to treat with WPRT.

This is a QOL report, and not surprisingly, VBT comes out on top, particularly with GI toxicities, which let to better social functioning as well.

This is gratifying, as it proves that less is more as far as the adverse events are concerned. Of course, more importantly what is the efficacy data.

This was presented at ASCO 2008. At 3-years vaginal relapse occurred 0.9% in the VBT arm and 2.0% after EBRT (p=0.97), 3-year pelvic relapse was 3.6% and 0.7% (p=0.03), respectively. 3 year distant relapse was 6.4% in the VBT group and 6.0% in the EBRT group (NS). No difference in 3-year OS (90.4% vs. 90.8% p=0.55) and RFS (89.5% vs. 89.1% p=0.38).

So now it's time to step back to the primary study endpoint, which was vaginal relapse, and unfortunately the stats section is a little vague here, probably because this is a QOL report not the clinical results. What it clear is that this was not designed as a non-inferiority trial for pelvic relapse, which to be honest, is what it probably should have been. If you are trying to say that vaginal brachytherapy is safe and as effective as WPRT, then the endpoint should be either pelvic relapse, distant relapse or overall survival. The pelvic relapses were actually significantly worse with VBT, thought the absolute difference was small (~3%). What is important about this is that these patients are essentially unsalvageable, which may eventually show in the OS numbers (though I wouldn't hold my breath due to the power of the study and competing causes of death in this patient population).

That stated, clearly VBT is an option for these patients, and this study, with relatively minor flaws in comparison to others supports the approach.

3 articles on Lancet Online First

Three article of interest in this week's Lancet online:

1. Publication of the SPCG-7/SFUO-3 trial of androgen deprivation +/- radiation therapy in locally advanced prostate cancer. This trial was presented at ASTRO 2008, and was one of the highlights of the plenary session. 873 patients with largely T3 tumors were treated with indefinite ADT, and were subsequently randomized to RT or no further intervention. They demonstate a biochemical, cancer-specific and overall survival benefit.

While to believers this is a "tell us something we don't already know" moment, there are plenty of non-believers out there, and this trial fits into a much needed gap in the literature in the treatment of high-risk prostate cancer.

Then there is publication of two components of the MRC - ASTEC trial in Endometrial cancer-

2. The first is a question of lymphadenectomy. This is a randomized trial of TAH-BSO + washings and palpation of the PA nodes +/- Lymphadenectomy, with a sizable sample size (n=1408). Contrary to prior non-randomized reports (particularly out of Duke), this trial finds no benefit to lymphadenctomy beyond TAH-BSO. In fact, the HR is in the wrong direction, and was worse in the subsets where more nodes were harvested.

While there are significant differences with the surgical approach in the US and Europe, this trial seriously challenges this approach.

3. The second question is one of radiotherapy. This is actually a report of the ASTEC trial and a canadian trial (NCIC CTG EN.5). Again a sizeable sample (n=905), randomized patients with intermediate to high risk, early stage endometrial cancer (any stage grade 3, IC any grade) to TAH-BSO to EBRT vs Observation. An important consideration is that a sizeable proportion (53%) received a brachytherapy boost to the vaginal cuff, outside of the randomization.

Not surprising, given findings from the PORTEC 1 and 2 trials, in addition to GOG 99, there was no survival difference. Local control was not formally evaluated in an actuarial fashion, however did seem to be improved. While there are no perfect studies examining this issued (at least from the rad onc's perspective), this again suggests that vaginal brachytherapy alone may be enough for the majority of early stage endometrial cancers.