D. Brabbins

Improved outcome at 10 years for serous-papillary/clear cell or high-risk endometrial cancer patients treated by adjuvant high-dose whole abdomino-pelvic irradiation

PURPOSE The aim of the study was to evaluate the 10-year treatment outcome of utilizing adjuvant high-dose whole abdominal irradiation (WAPI technique) with a pelvic/vaginal boost in patients with stage I-III endometrial carcinoma at high risk for intra-abdominopelvic recurrence, including serous-papillary and clear cell histologies. MATERIAL AND METHODS In a prospective nonrandomized trial, 132 patients were treated with adjuvant WAPI between November 1981 and October 2001. Forty-three patients (32%) were 1998 FIGO stage I-II and 89 (68%) were stage III. Pathological features included the following: 66 (52%) with deep myometrial invasion, 50 (38%) with positive peritoneal cytology, 89 (67%) with high-grade lesions, 25 (19%) with positive pelvic/para-aortic lymph nodes, and 58 (45%) with serous-papillary or clear cell histology. RESULTS The mean follow up was 6.4 years (range 0.6-16.1). For the entire group, the 5- and 10-year cause-specific survival (CSS) was 77 and 72%, whereas the disease-free survival (DFS) was 55 and 45%. When stratified by histology the 5- and 10-year CSS for adenocarcinoma was 75 and 70%, while serous-papillary/clear cell was 80 and 74% (P = 0.314). The 5- and 10-year DFS for adenocarcinoma was 59 and 49%, whereas serous-papillary/clear cell was 49 and 38% (P = 0.563). For surgical stages I-II, the 5-year CSS was 83% for adenocarcinoma and 89% for serous-papillary (P = 0.353). For stage III, it was 73 and 62% (P = 0.318), respectively. Forty-six patients (35%) relapsed. The first site of failure was the abdomen/pelvis in 27/46 (59%). When stratified by histologic variant, 34% of patients with adenocarcinoma and 41% with serous-papillary developed recurrent disease. In multivariate regression analysis only advancing age was of prognostic significance for CSS (P = 0.025) and DFS (P = 0.026). Chronic grade 3/4 GI toxicity was seen in 14%, and 2% of patients developed grade 3 renal toxicity. CONCLUSION High-dose adjuvant WAPI is very effective treatment with excellent 10-year results for stage I-III endometrial carcinoma with risk factors for intra-abdominopelvic recurrence, including serous-papillary or clear cell histology. The low long-term complication rate with high CSS makes high-dose WAPI the treatment of choice for these patients with significant comorbidities.

Ten-year outcome including patterns of failure and toxicity for adjuvant whole abdominopelvic irradiation in high-risk and poor histologic feature patients with endometrial carcinoma.

PURPOSE To evaluate the long-term results of treatment using adjuvant whole abdominal irradiation (WAPI) with a pelvic/vaginal boost in patients with Stage I-III endometrial carcinoma at high risk of intra-abdominopelvic recurrence, including clear cell (CC) and serous-papillary (SP) histologic features. METHODS AND MATERIALS In a prospective nonrandomized trial, 119 patients were treated with adjuvant WAPI between November 1981 and April 2000. All patients were analyzed, including those who did not complete therapy. The mean age at diagnosis was 66 years (range 39-88). Thirty-eight patients (32%) had 1989 FIGO Stage I-II disease and 81 (68%) had Stage III. The pathologic features included the following: 64 (54%) with deep myometrial invasion, 48 (40%) with positive peritoneal cytologic findings, 69 (58%) with high-grade lesions, 21 (18%) with positive pelvic/para-aortic lymph nodes, and 44 (37%) with SP or CC histologic findings. RESULTS The mean follow-up was 5.8 years (range 0.2-14.7). For the entire group, the 5- and 10-year cause-specific survival (CSS) rate was 75% and 69% and the disease-free survival (DFS) rate was 58% and 48%, respectively. When stratified by histologic features, the 5- and 10-year CSS rate for adenocarcinoma was 76% and 71%, and for serous papillary/CC subtypes, it was 74% and 63%, respectively (p = 0.917). The 5- and 10-year DFS rate for adenocarcinoma was 60% and 50% and was 54% and 37% serous papillary/CC subtypes, respectively (p = 0.498). For surgical Stage I-II, the 5-year CSS rate was 82% for adenocarcinoma and 87% for SP/CC features (p = 0.480). For Stage III, it was 75% and 57%, respectively (p = 0.129). Thirty-seven patients had a relapse, with the first site of failure the abdomen/pelvis in 14 (38%), lung in 8 (22%), extraabdominal lymph nodes in 7 (19%), vagina in 6 (16%), and other in 2 (5%). When stratified by histologic variant, 32% of patients with adenocarcinoma and 30% with the SP/CC subtype developed recurrent disease. Most failures for either histologic group occurred within the abdominopelvic region. However, one-third of the adenocarcinoma recurrences were in the lung. Multivariate regression analysis (age, surgical stage, grade, myometrial invasion, histologic type, lymph node status, and peritoneal cytology) demonstrated age (p = 0.019) and surgical stage (p = 0.036) to be of prognostic significance for CSS; age (p = 0.036) was the only significant prognostic factor for DFS. Grade 1-2 gastrointestinal and hematologic acute toxicities were common. Asymptomatic bibasilar scarring on chest X-ray and mild elevation of liver enzymes were seen in almost 50% of the patients. Even though chronic toxicities were less frequent, 12% developed Grade 3-4 gastrointestinal and 2% Grade 3 renal toxicities. CONCLUSION Adjuvant WAPI is very effective treatment with excellent 10-year results for Stage I-III endometrial carcinoma with risk factors for intra-abdominopelvic recurrence, including SP or CC histologic variants, deep myometrial invasion, high grade, nodal involvement, and positive peritoneal cytology. The low long-term complication rate with high CSS rate makes WAPI the treatment of choice for these patients with significant comorbidities.