Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: A randomized clinical trial

The role of systematic aortic and pelvic lymphadenectomy in patients with optimally debulked advanced ovarian cancer is unclear and has not been addressed by randomized studies. We conducted a randomized clinical trial to determine whether systematic aortic and pelvic lymphadenectomy improves progression-free and overall survival compared with resection of bulky nodes only. Methods: From January 1991 through May 2003, 427 eligible patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB-C and IV epithelial ovarian carcinoma were randomly assigned to undergo systematic pelvic and para-aortic lymphadenectomy (n = 216) or resection of bulky nodes only (n = 211). Progression-free survival and overall survival were analyzed using a logrank statistic and a Cox multivariable regression analysis. All statistical tests were two-sided. Results: After a median followup of 68.4 months, 292 events (i.e., recurrences or deaths) were observed, and 202 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for first event was statistically significantly lower in the systematic lymphadenectomy arm (hazard ratio [HR] =.75, 95% confidence interval [CI] = 0.59 to 0.94; P =.01) than in the no-lymphadenectomy arm, corresponding to 5-year progression-free survival rates of 31.2 and 21.6% in the systematic lymphadenectomy and control arms, respectively (difference = 9.6%, 95% CI = 1.5% to 21.6%), and to median progression-free survival of 29.4 and 22.4 months, respectively (difference = 7 months, 95% CI = 1.0 to 14.4 months). The risk of death was similar in both arms (HR = 0.97, 95% CI = 0.74 to 1.29; P =.85), corresponding to 5-year overall survival rates of 48.5 and 47%, respectively (difference = 1.5%, 95% CI = -8.4% to 10.6%), and to median overall survival of 58.7 and 56.3 months, respectively (difference = 2.4 months, 95% CI = -11.8 to 21.0 months). Median operating time was longer, and the percentage of patients requiring blood transfusions was higher in the systematic lymphadenectomy arm than in the no-lymphadenectomy arm (300 versus 210 minutes, P <.001, and 72% versus 59%; P =.006, respectively). Conclusion: Systematic lymphadenectomy improves progression-free but not overall survival in women with optimally debulked advanced ovarian carcinoma

Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis

No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46–1.21, P=0.16) and death (HR=0.85, 95%CI=0.49–1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=–3.4–14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=−7.0–9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival

Expression of Glucose Transporter-1 in Cervical Cancer and Its Precursors

Objective. Increased glucose uptake and utilization is a known phenomenon exhibited by malignant cells. Overexpression of the glucose transporter protein family is thought to be the principal mechanism by which these cells achieve up-regulation. Our purpose is to determine glucose transporter-1 (GLUT 1) expression in squamous carcinoma of the cervix and precursor lesions. Methods. Archival histologic sections were obtained from 31 cases of invasive squamous cell carcinoma (SCC) of the uterine cervix, 15 cases of high-grade cervical intraepithelial neoplasia, 5 cases of low-grade, and 9 normal cervices. Immunohistochemistry for GLUT 1 protein was performed using polyclonal GLUT 1 antibody (Dako, Carpinteria, CA) and the labeled streptavidin–biotin procedure. Results. Compared to the internal control, the pattern of staining varied from weak (1+) to strong (3+) reactions. In normal cervix, 1+ GLUT 1 staining was seen in the basal cells of the squamous epithelium. All 31 (100%) cases of SCC were positive for GLUT 1. Positive reactions seemed more intense in tumor cells that were farther away from the stromal blood supply. There was a correlation between intensity of reaction for GLUT 1 and histologic grade of tumor ( P = 0.0027) and with progression from normal or dysplastic lesions to invasive cancer ( P = 0.0001). Intensity was a predictor of the presence of poorly differentiated tumor type. Low-grade CIN staining was seen in less than one-third of the epithelium, while in high-grade lesions the reaction was present in over one-half of the epithelium. Conclusions. GLUT 1 is overexpressed in cervical carcinoma. The process appears to be related to grade of tumor but not to the progression from preneoplastic lesions. The results suggest that GLUT 1 overexpression is a late phenomenon in cellular transformation. Furthermore, the possible relation of expression to tumor blood supply suggests that the malignant cells may have an adaptive environmental ability to compensate for a compromised microenvironment