Uterine Cancer Flashcards
What data do we have that pelvic radiation could help with local control of advanced endometrial cancer when combined with chemotherapy, but didn’t show PFS difference?
GOG 258, control 6 chemo vs. exp EBRT + 4 chemo. PFS NS, no subgroup benefited, significantly less cuff and LN recurrence but 6 chemo had less distant recurrence. Stage I/II CCC and USC included, as well.
For high-risk early stage uterine cancer, what is data for pelvic radiation over 3 cycles of chemotherapy with cuff brachytherapy?
GOG 249, 601 patients, they had HIR endometrioid patients, stage II, plus serous or clear cell stage I-II. Patients here that would not have been in PORTEC-2, it’s totally different patient population. Control EBRT vs. 3 chemo + cuff RT. Chemo-cuff not superior for RFS/OS at all, double the LN recurrence in chemo-cuff group (9%). You would think distant recurrence would be better but no distant recurrence difference. Toxicities higher in exp. arm. So chemo-cuff was a total failure here. If there is anyone we think chemo would have helped, it would be serous or clear cell, but no strong evidence that these patients had a benefit, although slightly lower HR. This study has not likely changed anyone’s practice.
What data do we have for HER2NEU inhibition in advanced USC?
Phase 2 trial by Fader, improved PFS with Herceptin like 8 months for stage III/IV in HER2/neu overexpressing tumors, 3 months for recurrent, when added to carbo/taxol.
What established the importance of chemotherapy in high-risk uterine cancer?
PORTEC-3, control RT vs. exp. RT + 4 chemo. improvement in PFS with exp. arm that was sig., most pronounced in stage III and serous.
What data do we have that MIS staging of uterine cancer is safe and doesn’t negatively affect survival?
LACE, equivalence trial, looked at clinical stage I endometrial cancer, TLH vs. TAH, DFS/OS essentially identical. LAP2, noninferiorty trial, TLH vs. TAH, showed feasibility with regards to complications, LN removal, staging, conversion. The trial fell short of protocol-definied noninferiority with 11.4% vs. 10.2% recurrence, and OS was identical.
What data do we have to support SLND safely replacing full LND for staging in endometrial cancer?
SENTI-ENDO was the first, used T99 and blue dye, sensitivity and NPV were very high, and 8% of the LNs would have been missed on conventional section. When you do SLND, you will find more positive nodes. FIRES trial more modernly used ICG dye, prospective cohort study, SLND followed by full LND. 86% at least one side mapped, 52% both. 36 of these patients with positive LNs which was caught by SLND in 35 (97% PPV). 258 patient with negative SLN, 257 truly negative so NPV 99.6%. So SLN could use 3% of positive LNs but expose patients to much less morbidity and can safely replace. 29% were type IIs in this trial, not huge but decent number. The SENTOR trial suggested good sensitivity in high-grade disease, as did the SHREC trial, both similarly designed.
For high-intermediate risk, what data supports vaginal brachytherapy over EBRT?
Thought was, if most of the recurrences are vaginal and most of the toxicity is GI, can we thread the needle here. The big thing about this study, they on purpose didn’t have people staged, that makes these studies a little harder to generalize. Population was:
- > 60 1B g1,g2
- > 60 1A g3
- Stage II
PORTEC-2, control was staging (only clinical LN) + EBRT vs. exp. same + VCB. Primary outcome was vaginal recurrence, it was noninferiority trial. Similar DFS/OS, similar vaginal recurrences, but more side effects with EBRT.
Why don’t we give triplet chemotherapy in advanced endometrial cancer in addition to surgery and RT?
In part, GOG 184, control AP, exp. TAP, no differences in PFS, much more toxicity with TAP.
What data do we have for chemotherapy for advanced stage leiomyosarcoma?
GOG 87, one arm Gemzar/Taxotere looking at ORR with metastatic leiomyosarcoma. It was 36% and median PFS was 4-5 months.
I think, more recently, you have to hang your hat on the GEDDIS trial, advanced sarcomas, 70-80 odd uterine leiomyosarcomas, zero PFS/OS difference between adriamycin and Gem/Taxotere. More toxicity with the doublet. So I think Adria wins for now. What if it recurs? Then Gem/Tax. If that doesn’t work? Ifos, trabectidin, pazopanib. If you get that far, I think you’re done.
What data do we have for chemotherapy for early stage leiomyosarcoma?
Not much, lots of retrospective data, most of it showing no PFS/OS differences seen for stage I, I think Littell’s data with over 100 stage I uLMS and zero difference with observation probably tells the tale. GOG 277 tried to answer this question but sounds like accrual death, didn’t see any PFS/OS differences at closing analysis.
Stage II, which remember has pelvic spread and is not uterine contained, is lumped with stage III. But don’t think much data outside of some stuff lumped with stage I.
What data do we have for doublet therapy with Ifos and Taxol over Ifos in uterine carcinosarcoma?
GOG 161, phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma. Improvement of 2 months in PFS, 5 months in OS, but with notable toxicities (neuropathy).
What data do we have for EBRT with HIR endometrial cancer?
GOG 99, 392 women, phase III trial in women with stage I and II endometrial cancer (high-risk histologies excluded) for surgery with or without EBRT 5040 cGy in HIR.
2yr DFS significantly improved, largely because of decreased pelvic recurrences, and 4yr OS higher but NS.
Then they did a post-hoc analysis and determined a high-intermediate risk endometrial cancer that benefited the most from RT. “There were a lot of patients never at risk, we just need to define the right group and we’ll find benefit.” However, you can cherry pick at this point, you didn’t prespecify, so you’re not sure if it’s repeatable. It’s no longer randomized data, it’s been broken!
Risk factors - (1) Grade 2/3 tumor, (2) LVSI, (3) outer-third myometrial invasion.
Patients were included if: (1) 70+ w/1 RF, (2) 50-70 w/2 RF, (3) <50 w/3 RF.
What we DO have is evidence of harm…GI complications particularly, SBOs, low grade issues, you have to consider this.
PORTEC is on another card but TAH, no LND, they started with stage IB g1, all g2, stage IA g3 and randomized to EBRT vs. none. Again, decreased recurrence, most of which was to vagina, but more deaths in the EBRT group. Lots of women die “with endometrial cancer” vs. “from endometrial cancer.” So it’s just survival…trying to get them good outcomes overall. Again, some late GI toxicities that were sucky.
What data is there for deferring LND based off of intraoperative tumor characteristics?
Mayo Criteria Retrospective: 328 patients with g1-2, myometrial invasion < 50%. LND was performed in ~half of cases with 5% LN positivity. Of note, no patient with tumor diameter < 2 cm had positive LNs or died of disease within 5 years. They felt it would be safe to defer LNs in these patients with frozen diagnosis. Several studies have validated this approach, although it is felt frozen at Mayo is uniquely comprehensive compared to other settings.
What is our data establishing women who meet high-intermediate risk for recurrence and establishing that a majority of the recurrence were in the vaginal vault and that treatment could reduce locoregional recurrence.
PORTEC-1 and GOG 99. PORTEC-1 showed EBRT in stage 1 EC reduces locoregional recurrence but has no impact on OS, plus increases treatment-related morbidity. They suggested postoperative radiotherapy was not indicated in patients with stage-1 < 60 y/o and stage IA g2. GOG 99 had similar findings in a different risk group (separate card for this).
What data defined the surgicopathologic findings in surgically staged endometrial cancer and made surgical staging with lymph node dissection the standard of care.
GOG 33 was observational study, serially staged clinically stage I endometrial cancers with TAH/BSO, pelvic and paraaortic LND, some 600 something patients. They found many people with disease outside of the uterus, 5% adnexa, 9% PLN, 6% PALN, etc., with 22% in all having disease outside the uterus. It also showed how grade related to depth of invasion, as well as that pelvic LN involvement predicted PA LN involvement, with small numbers of isolated PA node positivity. Finally, the most classic finding was how grade and DOI directly related to LN status.
