Risk grouping in stage IB squamous cell cervical carcinoma

OBJECTIVES: To test the Gynecologic Oncology Group (GOG) prognostic criteria (based on stromal invasion, tumor size and vascular invasion) for early squamous cervical carcinoma (SCC) in an independent population and to evaluate the prognostic value of a simpler model. METHODS: We studied 221 patients who underwent radical hysterectomy and bilateral lymphadenectomy for stage IB SCC between 1987 and 1993. Adjuvant treatment consisting of radiotherapy and/or chemotherapy was given in case of large tumor size, positive lymph nodes or invasion into the parametria. Histological slides from all patients were reviewed by one pathologist. RESULTS: The GOG criteria divided the patients from our population in a small low risk group (3-year relapse-free rate (RFR) of 100%), a small high risk group (RFR of 57%) and a bigger intermediate risk group (RFR of 80-90%). These results are in good agreement with those of the original publication. A risk model based on 2 of the 3 factors used by the GOG may perform as well as the 3-factor model, especially when allowing interaction. Tumors measuring >2 cm and invading into the outer third of the cervical wall had a 5-year DFS of 56% compared to 93% for tumors measuring < or =2 cm or invading to less then the outer third of the cervical wall. CONCLUSION: The GOG criteria could be validated in this independent population. A model based on 2 of the 3 factors may perform as good.     

Modified radical hysterectomy in the treatment of early squamous cervical cancer

OBJECTIVE: The aim of this study was to evaluate the results of modified radical hysterectomy in the treatment of early cervical cancer. MATERIAL AND METHODS: A retrospective chart review of 56 patients with stage I (IA in 35, IB in 21) squamous cervical carcinoma treated with modified radical hysterectomy and followed for a minimum of 5 years (mean, 12 years; range, 5.1-29) was conducted. All pathology slides were reviewed for tumor size, grade, depth of invasion, and lymph-vascular permeation. RESULTS: The mean depth of invasion was 0.5 cm (range, 0.1-2.5 cm), and the mean tumor size was 1.1 cm (range, 0.1-7 cm). Only 3 patients (5.4%) had positive nodes. None of the patients with tumors 2 cm or less in size had positive nodes, whereas 33.3% of the patients with tumors more than 2 cm in size had positive nodes. A recurrence developed in 2 patients (5-year recurrence rate of 3.6%). There were 10 deaths during the entire follow-up period, but only 2 were related to cervical cancer. The disease-specific and overall 5-year survival rates were 96.4 and 94.6%, respectively. The disease-specific 5-year survival rate was 100% among the 47 patients with tumors 2 cm or less and 75% for the 9 patients with tumors larger than 2 cm. Univariate analysis identified stage, lymph node status, and tumor size as statistically significant prognostic factors for overall survival. Tumor grade, lymph-vascular permeation, and depth of invasion (1-3 mm vs >3 mm) were not statistically significant for overall survival. CONCLUSIONS: Modified radical hysterectomy appears to be effective surgical therapy for patients with squamous cervical carcinoma 2 cm or less in size.     

子宫颈鳞癌Ⅰb～Ⅱa期患者预后预测系统的建立及其临床意义

目的分析子宫颈鳞癌Ⅰb~Ⅱa期患者的预后影响因素并建立预后预测系统,以探讨其在指导术后辅助治疗中的作用。方法回顾性分析接受手术治疗的306例Ⅰb~Ⅱa期宫颈鳞癌患者的临床病理资料,对影响其预后的因素进行单因素和多因素分析。结果306例患者的5年生存率为78 1%。单因素分析结果显示,与其预后有关的因素为淋巴结转移、病理分化程度、肿瘤直径、宫旁组织浸润、深肌层浸润和脉管内瘤栓(P<0 05);多因素分析结果显示,淋巴结转移、深肌层浸润、宫旁组织浸润是影响其预后的独立危险因素(P<0 05)。根据危险因素的不同建立预后预测系统,即将患者分为低危组、中危组和高危组3组,其5年生存率分别为90 3%、83 9%和43 1%。低危组(无危险因素或仅宫旁组织浸润)局部复发的发生率仅为2 2%;中危组(深肌层浸润或合并有宫旁组织浸润)局部复发的发生率为13 5%,远处转移的发生率为1 3%, 局部复发合并远处转移的发生率为0 6%;高危组(淋巴结转移或合并其他危险因素)局部复发和远处转移的发生率分别为25 9%和48 3%,局部复发合并远处转移的发生率为10 3%。结论淋巴结转移、深肌层浸润、宫旁组织浸润是影响Ⅰb~Ⅱa期宫颈鳞癌患者预后的独立因素;根据预后影响因素建立的预后预测系统有助于指导术后辅助治疗。     

A comparison of prognoses of FIGO stage IB adenocarcinoma and squamous cell carcinoma

OBJECTIVES: The objective of this study was to compare clinical and pathologic variables and prognosis of FIGO stage IB adenocarcinoma and squamous cell carcinoma of uterine cervix. METHODS: A retrospective review was performed of 521 patients with stage IB squamous cell carcinoma and adenocarcinoma of cervix who treated primarily by type 3 hysterectomy and pelvic and/or para-aortic lymphadenectomy at Hacettepe University Hospitals between 1980 and 1997. RESULTS: Age, tumor size, grade, depth of invasion, lymph node metastasis, parametrial, vaginal, and lymphvascular space involvement (LVSI) were not different between two cell types except number of the lymph nodes involved. Metastasis to three or more lymph nodes was significantly higher in adenocarcinoma. Overall and disease-free survival were 87.7%, 84.0% versus 86.4%, 83.1% for squamous cell carcinoma and adenocarcinoma, respectively (P > 0.05). The rate and site of recurrence were not different between two cell types. Multivariate analysis of disease-free and overall survival revealed independent prognostic factors as tumor size, LVSI, number of involved lymph node, and vaginal involvement. CONCLUSION: Prognosis of FIGO stage IB cervical cancer patients who were treated by primarily radical surgery was found to be same for those with adenocarcinoma and squamous cell carcinoma.     

Application of tumor markers CEA, TPA, and SCC-Ag in patients with low-risk FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix

OBJECTIVE: The aim of this study was to determine the potential clinical utility of tumor markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) in patients with FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix with low-risk clinicopathologic factors (negative lymph node metastasis, no lymphovascular space involvement, no bulky tumor size, no parametrial invasion, no deep stromal invasion, and well-differentiated cellular histology). METHODS: A retrospective study was performed on 558 patients with FIGO stage IB-IIA and pathology-proven invasive squamous cell carcinoma of the uterine cervix, treated at the Veterans General Hospital, Taipei, between December 1986 and November 1990. Serum specimens were drawn before operation. A total of 140 assessable patients were enrolled into the study (including 109 stage IB patients and 31 stage IIA patients; all patients had no clinicopathologic risk factors and had at least one tumor marker datum). Survival curves were constructed according to the Kaplan-Meier method and survival curves were compared using the log-rank test. RESULTS: In univariate analysis of survival, CEA, TPA, and SCC-Ag all have roles in the prediction of prognosis. In Cox proportional hazards model using CEA, TPA, and SCC-Ag as covariates, TPA demonstrated the most significant risk factor (P = 0.031). CONCLUSIONS: We concluded that preoperative evaluation of serum TPA might be of great value in the prediction of survival of patients without any clinicopathologic risk factors and this special group of patients should be paid much attention in the follow-up period. From this study, preoperative elevation of TPA defines a group of otherwise low-risk invasive cervical cancer patients who are at high risk for recurrence. Adjuvant therapy might be necessary for this special subset of patients. A prospective study with a larger sample should be conducted to prove this particular finding.     

Prognostic factors affecting disease-free survival in early-stage cervical cancer patients undergoing radical hysterectomy and pelvic-paraaortic lymphadenectomy

OBJECTIVE: This study was performed to identfy surgical and histopathologic prognostic factors that could predict 5-year disease-free survival (DFS) after patients underwent radical hysterectomy and pelvic-paraaortic lymphadenectomy for FIGO Stage I-II cervical carcinoma. METHODS: A retrospective review was performed for all patients undergoing primary radical hysterectomy and pelvic-paraaortic lymphadenectomy for Stage I-II cervical cancer at Ankara Oncology Hospital from 1995 to 2000. Clinical and pathologic variables including age, tumor size (TS), clinical stage, depth of invasion (DI), lymphovascular space involvement (LVSI), cell type, tumor grade, lymph node metastases (LNM), parametrial involvement, surgical margin involvement and pattern of adjuvant therapy were analyzed using univariate analyses. DFS was performed by the Kaplan-Meier method and the log-rank test. Independent prognostic and predictive factors affecting DFS were assessed by the Cox proportional hazard method. RESULTS: Ninety-three patients underwent primary type III radical hysterectomy and pelvic-paraaortic lymphadenectomy. Five-year DFS was 87.1%. LVSI, parametrial involvement and grade were the prognostic factors that independently affected survival. DFS was not significantly different for age, disease status of the surgical margins, tumor size, depth of invasion, cell type, pelvic lymph node metastases and adjuvant radiotherapy. CONCLUSIONS: LVSI, parametrial invasion and histologic grade 2-3 were independent prognostic factors in early-stage cervical cancer patients. Adjuvant radiotherapy in these patients provides no survival advantage.     

Prognostic factors of adenocarcinoma of the uterine cervix

OBJECTIVE: The prognostic importance of adenocarcinoma of the uterine cervix was investigated. Methods. One hundred ninety-three patients (144 had stage I disease, 41 stage II, and 8 stage III-IV) with invasive adenocarcinoma of the uterine cervix treated initially at the Aichi Cancer Center between 1964 and 1995 were studied. RESULTS: Of all the invasive cervical cancers, 8.8% were adenocarcinomas that had been increasing during the past decade. The overall 5-year survival for stage I was 88.8%, stage II 44.9%, and stage III-IV 0% In univariate analysis, the clinicopathological factors associated with overall survival and disease-free survival were age of patient, stage of disease, presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, tumor size, and intraperitoneal metastasis. Multivariate analysis performed in all cases identified the clinical stage of disease, the presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, and tumor size as the independent risk factors for recurrence and survival. In the analysis of stage I disease, lymph node metastasis and tumor size were the significant prognostic factors, while lymph-vascular space invasion and tumor size were the factors in advanced disease. Tumor grade and histological type were not associated with recurrence and survival. CONCLUSION: These results suggested the association of lymph node metastasis with the prognosis of early stage adenocarcinoma of the uterine cervix and lymph-vascular space invasion with the advanced stage. Tumor size was an independent risk factor throughout all stages.     

Prognostic factors in FIGO stage IB cervical cancer without lymph node metastasis and the role of adjuvant radiotherapy after radical hysterectomy

OBJECTIVES: The aim of this study was to evaluate the clinical and pathologic prognostic variables for disease free survival, overall survival and the role of adjuvant radiotherapy in FIGO stage IB cervical carcinoma without lymph node metastasis. METHODS: A retrospective review was performed of 393 patients with lymph node negative stage IB cervical cancer treated by type 3 hysterectomy and pelvic lymphadenectomy at the Hacettepe University Hospitals between 1980 and 1997. RESULTS: The disease free survival and overall survival were 87.6 and 91.0%, respectively. In univariate analysis, tumor size, depth of invasion, vaginal involvement, lympho-vascular space involvement (LVSI) and adjuvant radiotherapy were found significant in disease free survival. Overall survival was affected by tumor size, LVSI, vaginal involvement and adjuvant radiotherapy. Tumor size, LVSI and vaginal involvement were found as independent prognostic factors for overall and disease free survival in multivariate analysis. Disease free survival, recurrence rate and site did not differ between patients underwent radical surgery and radical surgery plus radiotherapy. CONCLUSION: Tumor size, LVSI and vaginal involvement were independent prognostic factors in lymph node negative FIGO stage IB cervical cancer. Adjuvant radiotherapy in stage IB cervical cancer patients with negative nodes provides no survival advantage or better local tumoral control.     

Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy

BACKGROUND: The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy. METHODS: A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors. RESULTS: Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined to the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI was the most important prognostic factor, and histologic type, depth of cervical stromal invasion, and tumor size were not related to survival. The survival of patients with a tumor extending to parametrium or pelvic lymph node(s) was adversely affected by histology of pure adenocarcinoma. When the tumor extended to common iliac or paraaortic nodes, patients' survival became quite poor irrespective of LVSI or histologic type of pure adenocarcinoma. Patients' prognosis could be stratified into low risk (patients with a tumor confined to the uterus not associated with LVSI: n = 80), intermediate risk (patients with a tumor confined to the uterus associated with positive LVSI, and patients with squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma associated with pelvic lymph node metastasis or parametrial invasion, and patients with common iliac/paraaortic node metastasis: n = 21) with an estimated 5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/- 9.7%, respectively. CONCLUSIONS: LN status, parametrial invasion, LVSI, and histology of pure adenocarcinoma are important histopathologic prognostic factors of cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma may be stratified by combined analysis of these histopathologic prognostic factors. Postoperative therapy needs to be individualized according to these prognostic factors and validated for its efficacy using randomized clinical trials.     

Determinants of increased risk for recurrence in patients undergoing radical hysterectomy for stage IB and IIA carcinoma of the cervix

From 1939 to 1977, 431 patients underwent radical hysterectomy as primary therapy for Stage IB or IIA carcinoma of the cervix at Memorial Sloan-Kettering Cancer Center. Only 11 patients were lost to follow-up at intervals of from 1 to 94 months. Assessment of gross and histologic extent of disease was correlated with the prevalence of nodal metastases and survival. Increasing tumor size, depth of invasion, and histologic grade were covariable and predictive of both lymph node metastases and recurrence. After stratifying for nodal metastases, adenocarcinoma cell type, the size of the primary tumor, depth of invasion into the cervix, and histologic grade were associated with decreased survival. For the 85 patients with documented recurrence of their carcinoma, the time to recurrence varied inversely with primary tumor size. Of 56 patients with documented recurrence and negative nodes at the time of their initial therapy, 10 patients (18%) were ultimately salvaged. None of the 29 patients with recurrent carcinoma and positive nodes at the time of their initial lymphadenectomy was successfully treated. Analysis of prognostic factors identifies a group of patients at high risk for recurrence and decreased survival for whom prospective trials of adjunctive treatment should be considered.     

Prognosis of early cervical cancer (FIGO Stages IA2, IB, and IIA) in northern Norway predicted by malignancy grading score and objective morphometric image analysis.

Recurrence of early-stage cervical cancer after primary surgery represents a considerable clinical problem, and, so far, few reliable markers for prediction of recurrence exist. Thus, the prognostic value of the malignancy grading score (MGS) classification system was evaluated in 82 patients with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stages IA2, IB, and IIA) and long-time follow-up (5-16 years). Recurrence or not, the likelihood of lymph node metastases and reproducibility of the MGS semiquantitative system were tested. The prognostic power of the MGS to identify high-risk cases prone to recurrence in patients lacking lymph node metastases at primary surgery was a main purpose of the present study. The semiquantitative MGS classification system was performed independently by 2 pathologists unaware of prognosis and clinical data using light microscopy. Routine hematoxylin and eosin sections from surgical specimens were used, and investigation area was defined in the deep part of the tumor. Data-based image analysis was also used to investigate if objective morphometric parameters could add any prognostic power to MGS. The 5-year survival for the whole patient group was 92%. Malignancy grading score of greater than 17 risk points was statistically highly significant in predicting relapse and lymph node metastases (n = 82). High-risk cases lacking lymph node metastases (n = 70) were also statistically associated with high MGS. Depth of invasion and vascular invasion were statistically related to recurrence. Objective image analysis of nuclear parameters was of no additional statistical value for the prediction of outcome. The MGS classification system proved to be a useful tool in predicting recurrence and lymph node metastases and, most importantly, was a predictor of high-risk patients without metastases at primary surgery.     

Assessment of pelvic lymph node micrometastatic disease in stages IB and IIA of carcinoma of the uterine cervix

The objective of this study was to assess the frequency of micrometastatic disease (MID) in pelvic lymph nodes (PLNs) in carcinoma of the uterine cervix (CUC) and to determine the risk of recurrence. The PLNs from 289 patients with CUC (IB and IIA) were studied. Each PLN was assessed via immunohistochemistry using a single histologic section (AE1/AE3). Metastatic deposits were measured and the disease status was classified into three groups: 1) absence of metastatic disease (MOD); 2) MID, one or more metastatic PLN with only isolated tumor cells and/or micrometastases (up to 2 mm); and 3) macrometastatic disease (MAD), presence of one or more metastatic PLN with macrometastases (more than 2 mm). Eleven patients (3.8%) were classified as having MID and 37 (12.8%) as having MAD. The 5-year disease-free survival (DFS) rates for MOD, MAD, and MID were 88.7%, 80.4%, and 50.0%, respectively (P < 0.001). The Cox proportional hazards model showed that MID was an independent variable for recurrence when adjusted for MAD, depth of tumor invasion, severity of inflammatory reaction, and use of adjuvant radiotherapy. We conclude that the frequency of MID in PLN was low. However, patients with MID presented a high risk of recurrence and reduced DFS.     

Prevalence and prognostic significance of COX-2 expression in stage IB cervical cancer

OBJECTIVES: To evaluate the prevalence of cyclooxygenase-2 (COX-2), correlation with various clinicopathologic factors and prognostic significance of COX-2 in stage IB cervical cancer patients. METHODS: 89 paraffin-embedded specimens of patients with stage IB cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy at King Chulalongkorn Memorial Hospital during 1 January 1997-31 December 2002 and were stained with polyclonal goat antiserum against COX-2 using immunohistochemical method. Medical records were reviewed; clinicopathological variables were retrieved and used for analysis. RESULTS: The prevalence of positive COX-2 expression in stage IB cervical cancer in this study was 49.4%. Positive COX-2 expression in cervical adenocarcinoma was higher than squamous cell carcinoma (86.7% versus 40.6%, P < 0.05) and significantly expressed when lymph node metastasis was presented (100% versus 46.4%, P < 0.05). However, COX-2 expression was possibly associated with parametrial involvement (80% versus 47.6%, P > 0.05). There was no correlation between COX-2 expression and patient's age, tumor size, depth of stromal invasion and lymphovascular space invasion. Five-year disease free survival and 5-year overall survival in patients with positive COX-2 expression were 81% and 98% which were not differed from patients with negative COX-2 expression (92% and 95%, P > 0.05). CONCLUSIONS: Strong correlation was found in cervical adenocarcinoma and lymph node metastasis. However, COX-2 expression failed to demonstrate as a significant prognostic factor in stage IB cervical cancer.     

Multivariate analysis of the prognostic factors and outcomes in early cervical cancer patients undergoing radical hysterectomy

OBJECTIVE: This study was performed to identify pathologic and clinical risk factors that best predicted 5-year recurrence-free survival (RFS) among patients with early-stage cervical carcinoma, treated by radical hysterectomy and pelvic lymphadenectomy. METHODS: The records of 197 patients with early-stage invasive cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy from 1990 to 1999 were retrospectively reviewed. Clinical and pathologic variables including age, tumor size (TS), clinical stage, depth of invasion (DI), lymphovascular space involvement (LVSI), cell type, tumor grade, lymph node metastases (LNM), parametrial invasion, surgical margin involvement, and pattern of adjuvant therapy were analyzed using univariate and multivariate methods to define those variables that best predicted RFS. RESULTS: Outer 1/3 invasion, LVSI, and LNM were identified as independent poor prognostic factors, which were used to define three prognostic groups: patients (n = 104) with good prognoses (LVSI (-) and LNM (-)), patients (n = 46) with intermediate prognoses (either LVSI (+) without outer 1/3 invasion or LNM (+) without LVSI), and patients (n = 47) with poor prognoses (LVSI (+) patients with outer 1/3 invasion). The estimated 3-year RFS for patients with LVSI and deeply invasive tumors regardless of nodal status and/or nodal metastases receiving adjuvant CT + RT was significantly greater than that for patients who received only adjuvant radiotherapy (80% vs. 49%, P = 0.048 in the group of patients with LVSI and deeply invasive tumors with positive nodes and without positive nodes; 87% vs. 36%, P = 0.013 in the group of patients with LVSI and deeply invasive tumors with positive nodes only). CONCLUSIONS: The multivariate analysis and prognostic grouping system maximally separated patients with early-stage invasive cervical carcinoma into groups with good, intermediate, or poor prognoses, with 3-year RFSs of 90%, 82%, 67%; and 5-year RFSs of 89%, 69%, 43%, respectively. CT + RT played a role in improving RFS among patients with LVSI and deeply invasive tumors and poor prognoses.     

Adenosquamous carcinoma of the cervix: prognosis in stage IB

The outcome of women with adenosquamous carcinoma of the cervix has been a controversial issue. To assess the prognostic significance of this cell type, the medical records of 29 patients with stage IB primary adenosquamous carcinoma of the cervix were reviewed. Twenty-six had cervical tumors measuring 3 cm or less. With a median follow-up of 60 months, the overall disease-free 5-year survival was 85%. Pelvic lymph node metastases were found in three of 19 patients (16%) with stage IB, and periaortic lymph nodes were negative in eight. A log-likelihood chi 2 test comparing lymphatic spread, recurrence rate, and 5-year disease-free survival in patients with stage IB disease and tumors less than 3 cm versus a similar group of 58 patients with pure squamous cell carcinoma of equivalent stage and comparable size treated during the same time disclosed no significant differences in any of the indicators analyzed. We conclude that stage IB adenosquamous carcinoma of the cervix does not differ in its metastatic potential or outcome from the more common pure squamous cell carcinoma.     

Patients with squamous cell versus adeno(squamous) carcinoma of the cervix, what factors determine the prognosis?

Patients with squamous cell carcinoma of the cervix FIGO stages IB to IV ( n = 306) were compared to patients with adeno(squamous) carcinoma ( n = 70). There was no difference between the mean ages of the groups. In the patients who underwent radical surgical treatment, whether or not in combination with radiotherapy ( n = 209), stepwise regression analysis showed that a positive lymph node status was the most unfavorable prognostic factor, followed by the histologic type (adeno(squamous) carcinoma) and the tumor diameter (> 3 cm). Vascular-space invasion had no additional prognostic value. Patient's age did not affect the prognosis. Distant metastases were not found to be more prevalent in the patients with adeno(squamous) carcinoma. In patients with adeno(squamous) carcinoma and positive lymph nodes, it is worth considering more intensive locoregional treatment than is usually prescribed for these patients and/or adjunctive chemotherapy, because there is a high risk of tumor recurrence.     

Surgical-pathological predictors of disease-free survival and risk groupings for IB2 cervical cancer: do the traditional models still apply?

OBJECTIVE: To evaluate how the independent predictors of recurrence for stage IB2 cervical cancers treated with up-front radical hysterectomy apply to established risk models. METHODS: Patients with IB2 cervical cancers diagnosed from 1990 to 2000 were identified from tumor registries of two institutions. Patients were classified into risk groups: high-risk (HR) (positive nodes, parametria, or margins), intermediate-risk (IR) (positive lymph vascular space involvement (LVSI) with any cervical stromal invasion (CSI), or (-) LVSI and > middle- CSI), or low-risk (LR) (absence of HR or IR characteristics). Disease-free survival (DFS) was estimated by Kaplan-Meier method and comparisons between subgroups were studied by log rank. A Cox proportional hazards model was used to determine independent predictors of recurrence. RESULTS: We identified 86 patients with stage IB2 tumors treated by RH. We found 34% of patients to be HR, 60% IR, and 6% LR. Of the 52 IR patients, 28 had (+) LVSI with superficial, middle, and outer 1/3 CSI, and 24 had (-) LVSI with middle or outer 1/3 invasion. Overall, postoperative adjuvant radiation (PRT) was used in 52% of the 86 patients, including 0/5 LR, 16/52 IR, and 29/29 HR patients. Univariate predictors of recurrence were pelvic nodal disease, (+) LVSI, (+) parametria, outer 1/3 CSI, and tumor size > 6 cm. Age, grade, histology, and the use of postoperative radiation were not associated with recurrence. Multivariate analysis identified LVSI as the only independent predictor of recurrence (RR 5.2, P = 0.03). Two-year DFS for LR, IR, and HR patients was 100%, 83%, and 60%, respectively. Only 4/24 (17%) IR patients with (-) LVSI got PRT compared with 12/28 (43%) of IR patients with (+) LVSI. The 2-year DFS for IR patients with (-) LVSI was 96%. IR (+) patients recurred more frequently with a 2-year DFS of 71%. CONCLUSIONS: Overall, 66% of patients with IB2 disease were classified as having low or intermediate-risk disease. IR patients with (-) LVSI and all LR patients did well with surgery alone. This study defines the independent importance of LVSI and questions the utility of published IR models when applied to stage IB2 cervical cancer.     

Histological criteria for the prognosis in patients with operated squamous cell carcinoma of the cervix

Histological criteria for the prognosis were examined in 718 surgical specimens with squamous cell carcinoma of the cervix which were subjected to uniform histological workup. In the distinction between the invasion front and the tumor center the tumor grading in the region of the invasion front had particular prognostic significance. A very pronounced dissociative tumor growth also had an influence on the 5-year survival rates. The poorest prognosis was registered with patients in whom an invasion of the carcinoma into blood vessels could be observed. Taking into account the inflammatory stroma reaction in the center of the tumor and at the invasion front, more favorable recovery results could be registered with a heavy inflammatory infiltration in the region of the invasion front. The increase in tumor volume lead to a deterioriation of the recovery rates. These poorer recovery rates were due to the increase of the macrometastases, whereas tumor cell embolization into lymph nodes did not significantly influence the recovery results.     

Prognostic value of p53 expression in stage IB1 cervical carcinoma

The purpose of this retrospective study was to evaluate the patterns of p53 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare p53 expression with clinicopathological findings, and to assess its prognostic value. 27 patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of p53 was studied immunohistochemically. Overexpression of p53 was detected in 33.3% of the tumors, low expression was seen in 11.1%, and negative expression was found in 55.6%. Deep cervical stromal invasion (> or = 1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when p53 overexpression was observed (p = 0.0315). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessels, squamous cell carcinoma antigen (> or = 2 ng/ml), and p53 overexpression had a significantly lower recurrence-free survival rate. None of these above factors obtained significance in the multivariate analysis. This study suggests that expression of p53 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.     

Lymphovascular and perineural invasion in the parametria: a prognostic factor for early-stage cervical cancer

OBJECTIVE: To estimate the impact of parametrial lymphovascular and perineural involvement on nodal metastasis and failure pattern of women with early-stage, surgically treated cervical cancer. METHODS: Clinical records and pathologic slides of 93 patients with early-stage cervical cancer (2 IA2, 52 IB1, 31 IB2, and 8 IIA) treated with radical hysterectomy and pelvic lymphadenectomy with or without paraaortic lymphadenectomy were reviewed. The study group comprised 80 patients with squamous cell carcinoma and 13 patients with adenocarcinoma of the cervix. Median follow-up time was 33 months. The association among the various histopathologic predictors of outcome was determined with chi2 analysis. The influence of the predictors on outcome was examined with log rank survival methods and the Cox regression model. RESULTS: The presence of parametrial lymphovascular space invasion is a predictor of disease in the pelvic (P<.001) and paraaortic (P<.05) lymphatics independently. Large tumor size (greater than 4 cm), parametrial perineural invasion, cervical lymphovascular space invasion, and tumor depth (greater than two thirds) were found to be simultaneous predictors of recurrence on multivariate analysis (P<.05). Using these four binary predictor variables, we have computed a model-based relative risk. Based on this model, the presence of perineural invasion in the parametria more than doubles the risk of recurrence in the cohort of patients with large (greater than 4 cm) tumors (P<.05). In a subset analysis of patients with negative nodal disease, parametrial perineural invasion and tumor size were independent predictors of poor outcome (P<.05). CONCLUSION: Presence of parametrial lymphovascular space invasion correlates significantly with the risk of nodal metastasis in women with early-stage cervical cancer. Parametrial perineural invasion is an independent poor prognostic factor. Histopathologic findings within the parametria are a valuable independent predictor of recurrence and thus may influence the selection of patients for adjuvant treatment.