Adjuvant radiation treatment in high-intermediate risk endometrial cancer patients: For the motion

Endometrial cancer represents the most common gynaecological cancer in developed countries, with early stage disease in 80% of the cases. Surgery (consisting of bilateral salpingo-oophorectomy and total hysterectomy) represents the reference treatment. Adjuvant treatment is based on prognostic factors, deriving from randomized studies, dividing patients (pts) into risk groups, mainly : low-risk, low-intermediate risk, high-intermediate risk (HIR) and highrisk endometrial carcinoma (EC). HIR criteria differ slightly between Gynecologic Oncology Group (GOG) trial 99 and PORTEC-2 study. GOG 99 identified four risk factors for recurrence: age, tumor grade 2 or 3, lymph-vascular space involvement, and invasion of the outer third of the myometrium. HIR group consisted of pts at least 70 year-old with one additional factor, or at least 50 year-old with 2 additional risk factors, or with 3 risk factors. PORTEC-2 study defined HIR as pts >60, grade 1 or 2, FIGO (1988) stage IC or IIA with at least 50% of myometrial infiltration or less deeply infiltrative grade 3 tumor. In this HIR category, 15% of the pts are at risk of recurrence. In this pt population, PORTEC-2 trial showed that prophylactic vaginal brachytherapy (PVBT) was as efficient as external irradiation (EBRT) to prevent vaginal recurrences. Estimated 5-year rates of vaginal recurrence were 1.8% for PVBT and 1.6% for EBRT (P=0.74). Five year rates of locoregional relapse (vaginal recurrences and/or pelvic recurrences) were 5.1% and 2.1% (P=0.17). Moreover, quality of life was significantly better in the PVBT group. In the ASTEC/EN5 trial for intermediate and HIR with random assignment to EBRT or observation, PVBT was allowed if this was centre policy and if used in both arms. In 53% of the pts in the observation arm VBT was performed. This might explain the relative low rate of isolated vaginal and pelvic recurrence in the observation arm (6.1%, vs. 3.2% after EBRT). With this shift from external irradiation to less aggressive treatment, PVBT modalities have to be clearly stated. Even if BT is a very efficient treatment to prevent vaginal recurrences, there is no consensus so far on the optimal schedule particularly in HDR PVBT. Some clinical data, however, have evidenced a significant increase in vaginal recurrences after PVBT if BED10Gy < 30Gy. The length of irradiated vagina also has impact on long-term sequelae. PVBT aims at preventing recurrences at the level of the colpectomy and should not include more than half the vaginal height. Even if isolated vaginal recurrences can be salvaged in radiation-naïve patients, the treatment typically consists of a combination of EBRT and BT which is more intensive than initial postoperative PVBT and is associated with more toxicity. PVBT should be systematically recommended in HIR EC. In HIR-EC, if EBRT is able to reduce the 15-20% risk of locoregional recurrence to 5%, no survival benefit has been evidenced with a significant impairment in quality of life. The use of EBRT will thus be used only for the 15% of pts with high-risk or advanced disease. Advances in EBRT delivery using more sophisticated techniques such as intensity-modulated radiotherapy improve normal tissue sparing. The impact of new technologies on long-term toxicities remains unclear and will have to be assessed in future trials.