Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2019-07-20
Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer.
Abstract
Purpose
The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma.
Patients and methods
A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33-based high-intermediate-risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles.
Results
The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated.
Conclusion
Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.
Related Questions
How would you manage a patient in her 50s with FIGO IA clear cell carcinoma of the endometrium with extensive LVSI and ITCs in an obturator node after 6 cycles of carbo/taxol?
I would favor EBRT plus brachy boost.Here is a review and our treatment philosophy Musunuru et al., PMID 35248784
Despite the paucity of strong data showing benefit of chemotherapy + radiotherapy in patients with stage I-II high risk histology endometrial cancer, if you recommend treatment with both modalities, how do you determine treatment schedule?
For the purpose of this answer, I'll define high risk as serous, carcinosarcoma, undifferentiated, and dedifferentiated. Clear cell carcinoma can be considered and likely treated more by its molecular profile. As you indicate, there is little data to support the routine use of chemotherapy for FIGO ...
How would you manage an elderly but otherwise healthy patient with a high grade endometrioid uterine cancer with micro metastasis to a SLN, but otherwise confined to the uterus with superficial myometrial invasion?
With sentinel lymph nodes, pathology can show isolated tumor cells, micro metastasis, or macro metastasis. Our tumor board definitely has debated on how to handle micro metastasis in any patient, but especially those that are elderly, have treatment limited by social determinants, or have to travel ...
What is your approach to the adjuvant treatment of early-stage mixed-histology endometrial cancer with a significant clear-cell component?
Clear cell carcinomas are under-represented in most clinical trials and hence, clear evidence-based recommendations are difficult to make. Even a small percentage of clear cell is sufficient to label these as “high grade”. The recently published ASTRO guidelines mention that chemotherapy may not ben...
How would you treat a stage IA mixed carcinosarcoma/neuroendocrine tumor of the endometrium, negative LNs?
This is definitely an interesting question. Given the high-risk histology, I would want to ensure that a gynecologic pathologist has confirmed the histologic diagnosis as well as have imaging (either CT chest/abdomen/pelvis or PETCT skull base to mid-thigh) to ensure there is truly no extra uterine ...
Would uterine serosal involvement change your adjuvant treatment recommendation for a patient with Stage II grade 2 endometrial cancer?
Would recommend chemotherapy and vaginal brachytherapy. Had the patient had Stage II, Grade 2 disease (ignore the ITC for a moment), we would offer the patient pelvic radiation therapy alone based on GOG 249 and PORTEC 3 results, the latter of which showed a benefit of chemotherapy largely driven by...
How does number of ITC influence your approach to adjuvant RT for a surgically staged 1B endometrial cancer meeting HIR criteria?
Management of ITC only in the setting of SNLN is not defined well. We know ITC has a much better prognosis than micromets and macromets. We also know that even with ITC after SNLN bx only, there is risk of additional residual nodal disease left behind which may need to be addressed. What we don’t k...
What adjuvant therapy would you offer a patient with Stage II uterine serous carcinoma without lymph node sampling?
Since the major concern for UPSC is distant mets, these patients typically first receive 6 cycles of carboplatin/taxol after surgery at our institution. If the patient tolerates it without significant toxicity and re-staging scans are clear, we would then offer whole pelvis RT (45 Gy in 25 fractions...
How would you treat a high intermediate risk stage IA grade 2 endometrial ca?
If it is Stage IA, Grade 2 without additional risk factors, we recommend observation. It is not considered high intermediate risk.If it is Stage IA, Grade 2 with additional risk factors such as LVI or age 60+, we recommend a referral to radiation oncology to discuss. Anecdotally, most patients will ...
Do PORTEC-3 and GOG-258 change your approach to managing patients with high-risk or node positive endometrial cancer?
The ambiguous answer is "yes and no." The positive impact of RT on vaginal and nodal failure rates cannot be ignored and argues for a continued role for RT, probably external RT. There are a number of caveats relative to the interpretations of GOG 258. These include (but may not be limited to) high...
Do you offer vaginal cuff brachy alone, vaginal cuff brachy and chemo, or WPRT for surgically staged IB grade 3 endometrial cancer?
All patients who have stage IBG3 fall into the GOG249 eligibility criteria. However, it is important to recognize that patients within this group have broadly varying risks. First of all, serous cancers (which have a greater propensity to spread intraperitoneally and may demand variant-specific appr...