The PORTEC trilogy.

Top Line: Let’s rehash the best approach to post-operative management of high-risk endometrial cancer.
The Study: In a galaxy far far away, there are beings wondering why the heck we keep repeating endometrial trials for slightly different assortments of patients. Now we can add PORTEC-3 to their confusion. Patients were randomized to post-op pelvic radiation (48.6 Gy / 27) +/- chemo (concurrent cisplatin x 2 and adjuvant carbo/taxol x 4). Oh, and about half in each arm also received vaginal brachy for cervical involvement. In the spirit of inclusiveness, almost anything could buy you a ticket to get in this trial: stage I (if G3 with deep invasion and/or LVSI) through III endometrioid or any stage I-III clear cell or serous carcinoma. Shockingly [read with sarcastic tone], the number of survival events estimated was never reached. At 5 years, failure-free survival (FFS) was significantly improved with the addition of chemo (69% -> 76%) but overall survival (OS) was not (77% -> 82%). In planned subset analyses, the FFS advantage was carried by stage III disease (58% -> 69%), and the relatively few (n=120) patients 70 or older were the only group to see an OS benefit (58% -> 76%). To no real surprise, treatment related toxicity was 5x the rate with chemoradiation (60%) versus radiation alone (12%). 
Bottom Line: The addition of chemo to adjuvant pelvic radiation probably isn’t worth the toxicity for patients <70 years old with stage I-II disease (supported by GOG 249) and probably is worth it for those who are older and/or with stage III disease (supported by GOG 258). And we’ll channel every trial designer of the last decade to completely ignore PORTEC-2. Will someone please draw us a Venn diagram?


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