Gynecologic oncology 2014-11
Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria.
Abstract
Purpose
For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy.
Materials and methods
Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy.
Results
All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity.
Conclusions
Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response.
Related Questions
What dose and target volume do you use for neoadjuvant chemoRT in a patient with a locally advanced uterine/endometrial cancer involving parametria, cervix, and the uterine fundus (no side wall involvement) requiring downstage to be eligible for surgery?
Presuming that this is an endometrioid cancer - I would start with RT +/- chemo. There is potential for there to be sufficient shrinkage to facilitate brachytherapy boost. I do appreciate the link Dr. @Dr. First Last published, and would consider doing SBRT with a neoadjuvant dose how we would as pe...
How do you select the concurrent cisplatin dose and schedule when treating locally advanced endometrial cancer with chemoradiation?
For locally advanced endometrial cancer treated with pre operative or definitive intent, we use weekly cisplatinum at 40mg/m2. Vargo et al., PMID 25218303
How would you manage a large grade 2 endometrial adenocarcinoma with invasion into the parametria and upper vagina without nodal or metastatic disease?
PETCT and MRI. Preoperative chemo RT with EBRT plus brachy followed by surgery. Vargo et al., PMID 25218303
What HDR dosing would you use in the neoadjuvant setting of endometrial cancer?
This is our experience: I use 5 Gy x 3 to 4 fractions based on response with EBRT with EQ2 dose of around 65 Gy.Vargo et al., 25218303Iheagwara et al., PMID 30802615
How would you manage a clinically inoperable, stage IIIB, MMR deficient uterine cancer?
Tough situation and uncommon case. If definitely inoperable, your options are to do preoperative systemic therapy or preoperative radiation therapy. I often advocate for preoperative radiation therapy as these tumors tend to respond well to radiation, and you can save the standard-of-care chemothera...
How do you treat endometrial cancer in the setting of a pCR after neoadjuvant chemotherapy?
There is no data to guide. I would favor pelvic RT based on initial stage IIIB disease. We, at our institution, usually treat these patients with neoadjuvant chemo RT followed by surgery.https://www.ncbi.nlm.nih.gov/pubmed/25218303
What is your management strategy for unresectable endometrial cancer due to gross cervical involvement with parametrial extension?
Our approach is PETCT and MRI for staging. Neoadjuvant chemo RT with external beam and brachy to EQ2 dose of 65-70 Gy folllowed by extrafascial hysterectomy and then adjuvant chemotherapybelow is link to our published datahttps://www.ncbi.nlm.nih.gov/pubmed/25218303
Do you recommend concurrent chemotherapy with XRT for inoperable patients with stage I-II high-risk endometrial carcinoma?
For inoperable patients due to medical comorbidities, we have been reluctant to add chemotherapy because of the concern about side effects. For inoperable patients due to disease extent, we routinely add concurrent chemotherapy.https://www.ncbi.nlm.nih.gov/pubmed/25218303/
Is there a role for elective para-aortic nodal irradiation in endometrial cancer?
We treat in two scenarios:One is for patients who have had surgery done, have positive pelvic nodes on pathology, and PA nodes have not been dissected. For these patients, surgical series report a risk of pa nodal involvement of 40-50% and we treat pelvic and PA region after adjuvant chemotherapy.Th...