Endometrial Case

[Reaganite]

61 y/o, grade 3 adeno CA of the endometrium with "extensive necrosis", invading 4mm of 11mm myometrium with "extremely extensive LVSI" (never seen this terminology used in a path report before). 12 pelvic lymph nodes negative. Negative margins. No other uterine structures involved. Spoke to pathologist who said tumor looks "very aggressive." Vagina is very stenotic and will not accommodate even the smallest cylinder, so gonna need at minimum an external beam cuff boost.

Questions:

1. Would anyone treat the pelvis here?
2. How are you guys handling adequately surgically-staged 1bG3s? Was always taught to treat pelvis regardless of dissection and kinda wonder if this current patient should be treated more like one of these....

Appreciate your input!

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[Spiced Meats]

Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer--A pooled analysis of PORTEC 1 a... - PubMed - NCBI
I would absolutely treat the pelvis here both because of anatomy and the extent of LVSI. Substantial LVSI here serves as a surrogate for microscopic nodal involvement, 0/12 nodes wouldn't comfort me. On the GOG pooled analysis pelvic recurrence was more strongly predicted by extensive LVSI than MMI, age or grade.

 

[medgator]

Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer--A pooled analysis of PORTEC 1 a... - PubMed - NCBI
I would absolutely treat the pelvis here both because of anatomy and the extent of LVSI. Substantial LVSI here serves as a surrogate for microscopic nodal involvement, 0/12 nodes wouldn't comfort me. On the GOG pooled analysis pelvic recurrence was more strongly predicted by extensive LVSI than MMI, age or grade.

Having treated a couple pa nodal recurrences in pts who had had a good nodal dissection, would tend to agree, she should also be considered for 4-6 cycles of carbo/taxol

 

[Palex80]

Current pT1b G3 (old pT1c G3) should be treated with EBRT + chemo, if you want to give maximum treatment. This is what the data points to so far. In the future studies may show that EBRT can be omitted in case of chemo and adequate lymphadenectomy, however for the time being EBRT is s.o.c.

You could opt to treat your patient with EBRT to the pelvis, since she won't tolerate brachytherapy.

However your patient would have been included in PORTEC2 and (let aside the subgroup analysis) would not have benefitted from EBRT much.
Yet, I see your point as well as "Spiced Meat"'s point. LVSI is a known negative prognostic factor and 12 nodes are not that many; however do bear in mind, that PORTEC2 included patients without lymphadenectomy, meaning that there were probably some occult N+ patients there, who never got their nodes treated in any way if they were in the brachytherapy arm.
Quote from the paper:
"During surgery a peritoneal cytology specimen was obtained and abdominal exploration undertaken. Surgery consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy; clinically suspicious pelvic or periaortic lymph nodes were removed, but no routine lymphadenectomy was done."

I suspect that the additional benefit from EBRT is low, probably around 5% in terms of PFS at 5 years. Is it worth it? Your patient probably harbors quite an extensive risk of distant metastasis too, but you wont find anyone to give her chemo, since it's "only" pT1a

 

[seper]

Agree with WRPT for case 1 (see PORTEC 4 protocol, it goes over this exact situation).
Agree with WPRT+chemo for 1BG3, although there not an iota of evidence for chemo. Sometimes it is hard to find an oncologist to agree to give chemo.

 

[Spiced Meats]

Agree with WRPT for case 1 (see PORTEC 4 protocol, it goes over this exact situation).
Agree with WPRT+chemo for 1BG3, although there not an iota of evidence for chemo. Sometimes it is hard to find an oncologist to agree to give chemo.

FWIW those patients were included in the EORTC portion of the Hogberg pooled analysis. I think the EORTC study seperately met the primary endpoint of PFS benefit. Those patients are included in PORTEC 3 so hopefully we get an answer from there.

How are you all managing IIIB patients after complete resection? I've been extrapolating from Peters cervical criteria and treating with concurrent and pushing for adjvuant if there are other risk factors. The gyn oncs here rightfully emphasize this is an understudied group and do not like adjuvant chemo.

 

[Spiced Meats]

However your patient would have been included in PORTEC2 and (let aside the subgroup analysis) would not have benefitted from EBRT much.
Yet, I see your point as well as "Spiced Meat"'s point. LVSI is a known negative prognostic factor and 12 nodes are not that many; however do bear in mind, that PORTEC2 included patients without lymphadenectomy, meaning that there were probably some occult N+ patients there, who never got their nodes treated in any way if they were in the brachytherapy arm.
Quote from the paper:
"During surgery a peritoneal cytology specimen was obtained and abdominal exploration undertaken. Surgery consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy; clinically suspicious pelvic or periaortic lymph nodes were removed, but no routine lymphadenectomy was done."

I suspect that the additional benefit from EBRT is low, probably around 5% in terms of PFS at 5 years. Is it worth it? Your patient probably harbors quite an extensive risk of distant metastasis too, but you wont find anyone to give her chemo, since it's "only" pT1a

The GOG studies included a PLND and patients still benefited from EBRT. This patient would have fallen in the high int risk group of GOG 99. Also PORTEC 2 had a very low amount of patients with either grade 3 or LVI on the study so might be hard to apply it to these kind of patients.

 

[medgator]

FWIW those patients were included in the EORTC portion of the Hogberg pooled analysis. I think the EORTC study seperately met the primary endpoint of PFS benefit. Those patients are included in PORTEC 3 so hopefully we get an answer from there.

How are you all managing IIIB patients after complete resection? I've been extrapolating from Peters cervical criteria and treating with concurrent and pushing for adjvuant if there are other risk factors. The gyn oncs here rightfully emphasize this is an understudied group and do not like adjuvant chemo.

I've seen concurrent as well as sandwich which is what I do... 3 cycles ---> wprt+/-hdr cuff ---> 3 cycles

 

[RadOncDoc21]

I've seen concurrent as well sandwich which is what I do... 3 cycles --->'wprt+/-hdr cuff ---> 3 cycles

We use sandwhich but it's really tough on patients (chemo).

 

[seper]

For stage III rsected endometrial cancer, we prefer consolidation XRT after full dose of chemo. Other approaches are more toxic, IMHO.
Adjuvant chemotherapy and radiation therapy (RT) versus RT alone for women with high-risk endometrial cancer: Toxicity and quality-of-life results of the randomized PORTEC-3 trial. | 2015 ASCO Annual Meeting | Abstracts | Meeting Library

I have not heard people using Holdberg's study as evidence for chemo in stage I disease. It's pretty weak.

 

[evilbooyaa]

Agree with WRPT for case 1 (see PORTEC 4 protocol, it goes over this exact situation).
Agree with WPRT+chemo for 1BG3, although there not an iota of evidence for chemo. Sometimes it is hard to find an oncologist to agree to give chemo.

Agree with both of these sentiments as well. Especially with WPRT if vaginal cylinder isn't going to be feasible (with external beam cuff boost).

How are you all managing IIIB patients after complete resection? I've been extrapolating from Peters cervical criteria and treating with concurrent and pushing for adjvuant if there are other risk factors. The gyn oncs here rightfully emphasize this is an understudied group and do not like adjuvant chemo.

Sequential adjuvant chemo followed by radiation if no progression after 6 cycles Carbo/Taxol.

Every once in a while there will be a push to treat per 9708, concurrently, but it's a relatively small percentage of the time given concerns for toxicity.

Are you saying the gyn-oncs don't want to give ANY chemo for stage IIIB disease, or that they want to give it concurrently with radiation?

 

[Spiced Meats]

Agree with both of these sentiments as well. Especially with WPRT if vaginal cylinder isn't going to be feasible (with external beam cuff boost).



Sequential adjuvant chemo followed by radiation if no progression after 6 cycles Carbo/Taxol.

Every once in a while there will be a push to treat per 9708, concurrently, but it's a relatively small percentage of the time given concerns for toxicity.

Are you saying the gyn-oncs don't want to give ANY chemo for stage IIIB disease, or that they want to give it concurrently with radiation?

They are ok with concurrent not adjuvant. I think if other risk factors are present it just makes sense.

 

[Spiced Meats]

For stage III rsected endometrial cancer, we prefer consolidation XRT after full dose of chemo. Other approaches are more toxic, IMHO.
Adjuvant chemotherapy and radiation therapy (RT) versus RT alone for women with high-risk endometrial cancer: Toxicity and quality-of-life results of the randomized PORTEC-3 trial. | 2015 ASCO Annual Meeting | Abstracts | Meeting Library

I have not heard people using Holdberg's study as evidence for chemo in stage I disease. It's pretty weak.

Yeah I agree the peripheral neuropathy is brutal - this abstract really underlines that. Shouldn't be blanket approach.
What do you mean about Hogberg being weak?

 

[evilbooyaa]

They are ok with concurrent not adjuvant. I think if other risk factors are present it just makes sense.

I think IIIB endometrial (without other risk factors such as positive margins), obviously without lymph node involvement sequential chemo followed by RT or concurrent chemoRT are both reasonable. I think the gyn-oncs (unless they're actively managing the chemotherapy and see the patient during treatment) seem to underestimate the toxicity of platinum with RT for GI side effects.

Any other risk factors that you'd be extensively worried about? Outside of positive margins and cervical involvement, all the other major players (extensive LVSI, significant depth of myometrial involvement) would seem to put patients at higher risk of distant failure.