Three hundred forty‐five patients with invasive carcinoma of the uterine cervix, Stages Ib (211 patients) and II I (134 patients), underwent radical hysterectomy and pelvic lymphadenectomy. The influence of histologic factors including histologic subtype, maximum depth of cervical stromal invasion, degree of stromal invasion, longitudinal tumor diameter, lymph‐vascular space invasion, corpus invasion, parametrial invasion, vaginal invasion, and pelvic lymph node (PLN) metastases on survival were examined by multivariate analysis. Univariate analysis revealed that all the variables except corpus invasion and vaginal invasion were significant in survival (P < 0,05). Among these variables, however, PLN metastases, histologic subtype, and longitudinal tumor diameter were identified as independent and significant prognostic factors by multivariate analysis using Cox regression models. The prognostic index (PI), defined by the model (an indicator of the patient's place in the prognostic spectrum), was able to divide the patients into three prognostic groups. The key factors in the definition of these groups were (1) squamous cell carcinoma, small tumor diameter, and no PLN metastases for the good prognostic group and (2) PLN metastasis in two or more node groups, adenocarcinoma with one positive PLN group, or squamous cell carcinoma with one PLN group and large diameter for the poor prognostic group. These prognostic findings could predict the prognosis more precisely than that of clinical staging.
BACKGROUND Tumor angiogenesis is essential for tumor growth and metastases. Recently, microvessel density (MVD), a measure of tumor angiogenesis, has been found to have prognostic significance for predicting metastasis and survival in many tumor types. This study was conducted to determine how MVD was related to several clinicopathologic parameters and correlated with metastasis and survival in patients with endometrial carcinoma. METHODS From 1979 through 1989, 85 cases of clinical Stage I and II endometrial carcinomas treated initially by hysterectomy with pelvic lymph node dissection were reviewed histologically. All hysterectomy specimens were stained immunohistologically for factor VIII‐related antigen. MVD was counted in a ×200 field (×20 objective lens and ×10 ocular lens, 0.785 mm2 per field) in the most active area of neovascularization. Results were expressed as the highest number of microvessels identified within any single ×200 field. Statistical analysis included the Mann‐Whitney U test, Kruskal‐Wallis test of variance, and the Spearman rank correlation test. Survival was calculated using the Kaplan‐Meier method and differences in survival were analyzed using the log rank test. MVD and several other prognostic parameters were examined for their correlation with progression free survival (PFS) and overall survival (OS) by a multivariate analysis according to the Cox proportional hazards model. RESULTS MVD was significantly correlated with tumor grade (P = 0.0281), myometrial invasion (P = 0.0282), and lymph‐vascular space invasion (P = 0.0073). There was no correlation between microvessel count and lymph node status and stage. Patients with a high MVD (≥60) had significantly worse PFS and OS than those with a low MVD (<60) (log rank test, P = 0.0116 and P = 0.0096, respectively). Multivariate analysis showed that MVD correlated significantly and independently with PFS and OS. CONCLUSIONS In this study, MVD was found to be an independent prognostic factor for PFS and OS in patients with endometrial carcinoma. Cancer 1997; 80:741‐7. © 1997 American Cancer Society.
Of 107 patients with stage IIb cervical cancer who underwent laparotomy, 82 (77%) could be treated with radical hysterectomy (RAH) and pelvic-node dissection (PND). The remaining 25 patients were unsuitable for radical surgery because of para-aortic lymph node metastases, direct cancer invasion into the bladder muscle, and/or fixed enlarged pelvic lymph nodes (PLN): Such patients were treated with radiation therapy after laparotomy. Fifty-nine of RAH patients were given postoperative pelvic radiation because they had PLN metastases, parametrial invasion, and/or full thickness cervical stromal invasion. The overall 5-year survival of the patients undergoing RAH was significantly better than that of those who could not be treated with RAH (P < 0.001). In the RAH patients, parametrial invasion, which clinically defines stage IIb, was found only in 45%. Univariate analysis of histopathologic prognostic factors revealed that PLN metastasis, parametrial invasion, adenocarcinoma, and lymph-vascular space invasion significantly affected survival of the RAH patients (P < 0.05). Multivariate analysis using Cox's proportional hazards regression model, however, selected only PLN metastasis as a strong prognostic factor (P < 0.001). Concerning PLN metastasis patients with two or more positive nodal groups vs. 49%, P < 0.0001). The logistic regression analysis revealed that tumor diameter, parametrial invasion and lymph-vascular space invasion were independently correlated with PLN metastases in two or more nodal groups. The present data suggest that (i) the patients with massive pelvic extension of cancer cannot be cured by radiation therapy alone, (ii) the strong determinant of the prognosis of the patients undergoing RAH and PND is PLN metastasis. Therefore, for these patients with poor prognosic factors, other treatment modalities should be considered. From the present study it seems that planning RAH and PND for patients with stage IIb disease might make it possible to select poor prognostic subgroups, who have extra cervical extension or PLN metastases in two or more groups, and be useful in individualizing treatment.
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