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。     

High-risk group in node-positive patients with stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy and postoperative pelvic irradiation

OBJECTIVE: The goal of this study was to identify risk factors in patients with node-positive stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy with pelvic lymph node dissection and postoperative irradiation. METHODS: Two hundred forty-two patients with FIGO stage IB, IIA, and IIB cervical carcinoma underwent radical hysterectomy with pelvic lymph node dissection; pathological analysis of the surgical specimen showed positive lymph nodes in 59 patients. These 59 patients were further treated with postoperative radiotherapy. Eighteen patients were in stage IB, 4 in stage IIA, and 37 in stage IIB. Histological tumor type, tumor size, lymph-vascular space invasion, parametrium infiltration, number of positive nodes, and involvement of common iliac nodes were assessed for correlation with cancer recurrence. RESULTS: When all these variables were assessed in the Cox proportional regression analysis, parametrium infiltration (P = 0. 0199) and number of positive nodes (two or more nodes) (P = 0.0483) revealed the factor correlating significantly with disease-specific survival. Based on these two factors, node-positive patients could be divided into low-risk (n = 11), intermediate-risk (n = 29), and high-risk (n = 19) groups. The 5-year disease-specific survival for the low-risk group was 100% which was significantly better than the 39.1% for the high-risk group (P = 0.0012). CONCLUSION: For patients in the high-risk group, it may be worthwhile to consider new strategies to improve survival.     

Do the pelvic lymph nodes predict the parametrial status in cervical cancer stages IB–IIA?

The aim of this study was to determine whether the pelvic lymph nodes would predict the parametrial status in patients with cervical cancer stages IB1-IIA submitted to radical surgery and pelvic lymphadenectomy. To this end, we evaluated the relationship between positive and negative pelvic lymph nodes and their parametria. Our final purpose was to use this information to recommend the tailoring of the parametrial resection according to the status of pelvic lymph nodes to decrease the morbidity related with radical paratrectomy. From January 1996 to December 2001, 107 consecutive patients with cervical cancer stages IB1 and IIA were primarily treated by radical hysterectomy type III with systematic pelvic lymphadenectomy in a prospective study. Parametria were studied in two sections: the first included the tissue adjacent to the cervix, and the second the distal 2/3. Lymph nodes were routinary processed. Twenty-two patients (20.6%) had positive pelvic nodes and 16 patients (14.9%) had parametrial involvement, mostly by direct extension. Eight patients with positive pelvic nodes (36.4%) had parametrial involvement, whereas among 85 patients with negative pelvic nodes only eight patients (9.4%) had parametrial involvement (P < 0.001), most in internal parametria (62.5%). The sensitivity of pelvic lymph nodes for parametrial involvement was 50% and the positive predictive value was 36.4%, whereas the specificity was 84.6%; and the negative predictive value 90.6%. In the group of negative pelvic lymph nodes, only two patients (2.3%) had parametrial involvement beyond internal parametria. The univariated and multivariated analysis of prognostic factors was always significant but without a significant independent factor for positive parametria. Pelvic lymph nodes appear as good predictors of parametrial status, especially in node-negative patients, and could be used to decrease the paratrectomy in radical surgery.     

Number and distribution of pelvic lymph nodes and effect of surgical pathologic factors on pelvic lymph node status in patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection

PURPOSE OF INVESTIGATION: To report the number and distribution of pelvic lymph nodes and to identify surgical pathologic factors that best predict positive pelvic lymph nodes in patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection (RHND). METHODS: Data from the files of 126 patients with cervical carcinoma treated by RHND at the Soroka Medical Center from 1962 through 2005 were analyzed. RESULTS: The status of pelvic lymph nodes was known in 114 patients. The exact number of lymph nodes removed from the pelvis of each patient was known in 111 patients. The mean number of lymph nodes removed from the pelvis per patient was 26.6 (median 23; range 1-62). Positive pelvic lymph nodes were found in 35 (30.7%) of the patients with a mean of 3.4 (median 2; range, 1-15) positive pelvic lymph nodes per patient. In a univariate analysis, positive lymph vascular space invasion and positive parametrial and/or paracervical involvement were significant predictors of positive pelvic lymph nodes, whereas penetration > or = 50% of the thickness of the cervical wall and grade 2+3 were of borderline significance. In a multivariate analysis, positive lymph vascular space invasion was the strongest and the only significant predictor of positive pelvic lymph nodes, whereas positive parametrial and/or paracervical involvement was of borderline significance. CONCLUSIONS: In patients with early-stage cervical carcinoma treated with RHND, positive lymph vascular space invasion emerged to be the strongest and most significant predictor of positive pelvic lymph nodes.     

How important is removal of the parametrium at surgery for carcinoma of the cervix?

OBJECTIVES: The aims of this study were (1) to determine the incidence and factors predictive for pathologic parametrial involvement in clinical stage IA1/2 and IB1 cervical cancer after radical surgery and (2) to identify a population at low risk for pathologic parametrial involvement. METHODS: All patient information was collected prospectively and extracted from a cervical cancer radical surgery database. Selection criteria for surgery were generally based upon tumor size, with the cutoff for surgery between 3 and 4 cm. Parametrial involvement (PI) was defined as either positive parametrial lymph nodes (PMLN) or malignant cells in the parametrial tissue (PT) (including lymphovascular channels) by either contiguous or discontiguous spread. Statistical analysis included the chi2 test, the Wilcoxon rank test, and the Mantel-Haentzel test. RESULTS: Between July 1984 and January 2000, 842 patients underwent radical surgery for clinical stage IA1/2 and IB1 cervical cancer at our center. Forty-nine patients (6%) had positive pelvic lymph nodes. Thirty-three patients (4%) had pathologic PI, 8 in the PMLN and 25 in the PT (none had both). PI was associated with older age (42 vs 40 years, P < 0.04), larger tumor size (2.2 vs 1.8 cm, P < 0.04), higher incidence of capillary-lymphatic space invasion (85% vs 45%, P = 0.0004), tumor grades 2 and 3 (95% vs 65%, P = 0.001), greater depth of invasion (18.0 vs 5.0 mm, P < 0.001), and pelvic lymph node metastases (44% vs 5%, P < 0.0001). The incidence of PI in patients with tumor size < or =2 cm, negative pelvic lymph nodes, and depth of invasion < or =10 mm was 0.6%. CONCLUSION: Pathologic parametrial involvement in clinical stage IA1/2 and /IB1 cervical cancer is uncommon. Acknowledging that almost all patients with pelvic lymph node metastases and a high proportion of patients with tumor invasion >10 mm will receive adjuvant radiation regardless of the radicality of surgery, a population at low risk for pathologic parametrial involvement can be identified. These patients are worthy of consideration for studies of less radical surgery performed in conjunction with pelvic lymphadenectomy.     

Prognostic factors and failure pattern in lymph node-negative stage IB and II cervical carcinoma treated with radical hysterectomy and postoperative irradiation

The aim was to determine the prognostic factors and recurrence pattern in stages IB and II cervical carcinoma patients with negative pelvic lymph nodes. 224 patients with stages IB and II cervical carcinoma underwent radical hysterectomy (RH) from 1982 through 1995. Of 161 patients with negative lymph nodes, 65 patients received postoperative irradiation (RT) and 96 patients were given no further therapy according to surgical pathological findings. The overall 5-year disease-free survival was 94.1%. Two of 96 RH patients (2%) and 10 of 65 RH + RT patients (15%) had recurrence in pelvic and distant sites almost equally. Multivariate analysis revealed deep cervical invasion as the only independent prognostic factor. The 5-year disease-free survival was 98.8% for patients with shallow invasion and 85.8% for patients with deep invasion (p < 0.0001). It is worthwhile to develop new strategies for the lymph node-negative patients with deep stromal invasion.     

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.     

Early Stage Cervical Cancer: A Multivariate Analysis of Histopathological Prognostic Factors

Summary: A multivariate analysis of the histopathological prognostic factors in early stage carcinoma of the cervix was performed. A total of 140 patients were studied (Stage 1A 6, Stage IB 107, Stage 2A 27 patients). Five-year follow-up data were available for 124 patients and 10-year data for 76 patients. The histopathological factors considered were the histological type, lymph node metastases, tumour diameter, lymph vascular space invasion, parametrial invasion and corpus and vaginal invasion. Multivariate analysis identified lymph node metastases (p = 0.0003) and tumour diameter (p = 0.0016) as significant variables for survival at 5 and 10 years. There was a high incidence of occult parametrial invasion (20% in Stage IB and 37% in Stage 2A). Univariate analysis identified lymph node metastases (p < 0.0001), tumour diameter (p < 0.0001), lymph vascular space invasion (p = 0.0041) and parametrial invasion (p = 0.0024) as significant variables for survival at 5 years, with lymph node metastases, tumour diameter, lymph vascular space invasion remaining significant at 10 years. If there were 2 or more pelvic lymph node metastases the survival decreased considerably (up to 40% over 5 years). Microscopic parametrial invasion was identified in 20% of Stage IB and 37% of Stage 2A tumours. The critical period for recurrence was the first 2 years after surgery.     

Value of preoperative serum CA125 in early-stage adenocarcinoma of the uterine cervix without pelvic lymph node metastasis

OBJECTIVE: This investigation attempted to clarify the value of preoperative serum CA125 in predicting histopathological prognostic factors for early-stage cervical adenocarcinoma without lymph node metastasis. METHODS: This study initially surveyed 163 patients with clinical stage Ib or IIa cervical adenocarcinoma treated with radical hysterectomy and pelvic lymphadenectomy. Of the 163 patients, 116 had preoperative serum CA125 levels, and 14 had pelvic lymph node metastasis. The investigation group comprised 102 lymph node-negative patients. RESULTS: A cutoff value of 26 U/ml was obtained after the discriminant function analysis for identifying patients with positive lymph vascular space invasion (LVSI) or depth of stromal invasion > or =2/3 thickness. Multivariate analysis revealed that among the preoperative clinicopathological variables, including age, tumor size, parametrial invasion, and CA125 level, raised CA125 most significantly influenced the assessment of the LVSI (P = 0.040) and depth of cervical stromal invasion (P = 0.002). CONCLUSIONS: In early-stage cervical adenocarcinoma with negative pelvic lymph node metastasis, preoperative serum CA125 levels at the cutoff value of 26 U/ml impacted the determination of the poor histopathological prognostic factors.     

Prognostic factors in pathologic parametrium-positive patients with stage IB-IIB cervical cancer treated by radical surgery and adjuvant therapy

OBJECTIVE: The purpose of the present study was to identify prognostic factors and recurrent patterns in pathologic parametrium-positive patients with stage IB-IIB cervical cancers treated by radical surgery and adjuvant therapy. METHODS: The patient population consisted of 84 individuals presenting with stage IB-IIB cervical cancers and histologically proven parametrial invasion. All these patients were treated postoperatively with adjuvant external whole pelvic irradiation, combination chemotherapy, or chemoradiotherapy. RESULTS: The 5-year disease-free survival rate was found to be 67.2% and 5-year overall survival rate, 75.4%. Multivariate analysis revealed that vaginal invasion (p=0.0008), lymph node metastasis (p=0.002), and non-squamous histology (p=0.010) were independent indicators of the disease-free survival rates and that the vaginal invasion (p=0.009) and lymph node metastasis (p=0.011) were independent prognostic factors for the overall survival rates. The 5-year overall survival rate was approximately 90% for patients without these risk factors. Disease recurrence was observed in 26 patients (31.0%) with a median time of 16.5 months (range, 5-59 months) from the surgery. Hematogenous recurrences, including those in the lung, liver, and bone, were significantly higher in patients with non-squamous cell carcinomas (p=0.008). Distant lymph node recurrences were significantly higher in patients with positive pelvic lymph node and vaginal invasion (p=0.004 and p=0.023, respectively). Pelvic recurrences were significantly higher in patients with vaginal invasion (p=0.026). CONCLUSIONS: Vaginal invasion and lymph node metastasis are independent indicators for disease-free and overall survival rates in pathologic parametrium-positive patients with stage IB-IIB cervical cancer treated by radical surgery and adjuvant therapy. The survival rate is excellent in the patients without these risk factors. Hematogenous recurrence may be evident in patients with non-squamous cell carcinomas.     

A limited role for adjuvant radiotherapy after the Wertheim/Okabayashi radical hysterectomy for cervical cancer confined to the cervix.

BACKGROUND: The indications for radiotherapy after radical hysterectomy for early stage cervical cancer are changing. In the past only tumor outside the cervix was considered an indication for radiotherapy. Today adjuvant radiotherapy is also considered for an "intermediate-risk" group with tumor confined to the cervix but poor prognostic primary tumor parameters such as large tumor diameter, vascular space invasion, and deep stromal penetration. OBJECTIVE: The aims of this study were to determine the risk of isolated pelvic recurrences in an intermediate-risk group (GOG Study No. 92) and to analyze whether this group will theoretically benefit from adjuvant pelvic radiotherapy. PATIENTS AND METHODS: A retrospective analysis was performed on 271 patients with early cervical cancer treated by a radical hysterectomy in a uniform fashion in one institute. Radiotherapy was administered only when tumor was found outside the cervix. Tumor diameter, capillary lymphatic space invasion, and depth of stromal penetration were assessed in all patients. Recurrence pattern, disease-specific survival, and recurrence-free interval were determined in the intermediate-risk group and compared with the remaining patients of the group with tumor confined to the cervix. RESULTS: A significant difference in disease-specific survival (89% versus 97%, P < 0.03) and 5-year recurrence-free interval (86% versus 95%, P < 0.02) was noted in the intermediate-risk group (n = 56) compared with the total group with tumor confined to the cervix. Three patients in the intermediate-risk group died of disease with a pelvic recurrence. Two of these patients had a combined pelvic and distant recurrence. CONCLUSION: Our retrospective results fail to support a survival benefit of extending indications for adjuvant radiotherapy other than postive nodes, parametrial extension, and positive margins.     

The prognostic factors for patients with early cervical cancer treated by radical hysterectomy and postoperative radiotherapy

PURPOSE: This study was undertaken to evaluate the efficacy of postoperative radiotherapy (post-OP RT) and to investigate the prognostic factors for early-stage cervical cancer patients who were treated by radical surgery, and the pathological findings suggested a relatively high risk of relapse with surgery alone. MATERIALS AND METHODS: From January 1990 to December 1995, 222 patients with stage IB-IIA cervical cancer, treated by radical surgery and a full course of post-OP RT, were included in this study. The indications for post-OP RT were based on pathological findings, including lymph node metastasis, positive surgical margins, parametrial extension, lymphovascular permeation, and invasion of more than two-thirds of the cervical wall thickness. The radiation dose of external beam was 44-45 Gy to the whole pelvis and 50-54 Gy to the true pelvis. One hundred seventy-two patients also received intravaginal brachytherapy as a local boost. The minimal follow-up period was 2 years. RESULTS: The actuarial 5-year overall and disease-specific survival rates for all patients were 76 and 82%, respectively. The tumor control rate within the pelvis reached 94%, and distant metastasis was the major cause of treatment failure. Univariate analysis of clinical and pathological parameters revealed that clinical stage, bulky tumor size, positive lymph nodes, parametrial extension, and histologic type were significant prognostic factors. After multivariate analysis, only positive lymph nodes (P = 0.01), bulky tumor size (P = 0.02), and parametrial extension (P = 0.05) independently influenced the disease-specific survival (DSS). For patients with lymph node metastasis, the number and location of the nodal involvement significantly affected the prognosis. The 5-year DSS for patients with no, one, and more than one lymph node metastasis were 87, 84, and 61% (P = 0.0001), respectively. Patients with upper pelvic lymph node metastasis had a higher incidence of distant metastasis (50% vs 16% in lower pelvic node group, P = 0.03). In the subgroup of single lower pelvic nodal metastasis, the prognosis was similar to that of patients without lymph node involvement (5-year DSS 85% vs 87%, P = 0.71). CONCLUSION: Our results indicate that post-OP RT can achieve very good local control in stage IB-IIA cervical cancer patients whose pathological findings show risk features for relapse after radical surgery. The prognostic factors for treatment failure identified in this study can be used as selection criteria for clinical trials to test the effects of other adjuvant treatments, such as chemotherapy. Patients with a single lower pelvic lymph node metastasis have a relatively good prognosis and may not need adjuvant treatment beyond radiation therapy.     

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.     

Stage IB and IIA Cervical Cancer with Negative Lymph Nodes: The Role of Adjuvant Radiotherapy after Radical Hysterectomy

The records of 171 patients with lymph node-negative stage IB and IIA cervical cancer primarily treated with radical hysterectomy and pelvic lymphadenectomy from 1974 to 1992 were retrospectively reviewed to identify poor prognostic factors and evaluate the role of adjuvant pelvic radiotherapy. One hundred sixteen patients (68%) were treated with radical hysterectomy alone (RH) and 55 patients (32%) received adjuvant radiotherapy (RH + RT). Factors predictive of recurrence for the entire group of patients included lymph–vascular space invasion (LVSI) (P= 0.003) and grade 3 histology (P= 0.04). Patients receiving RH + RT were older and more likely to have outer third cervical wall invasion, LVSI, positive margins, ≥2 cm pathologic tumor size, and >4 cm clinical tumor size (allP< 0.05). Overall, 28 patients (16%) developed recurrent disease with no difference between RH and RH + RT groups. After controlling for confounding variables, patients with LVSI who received RH + RT were less likely to develop disease recurrence than patients receiving RH alone (P= 0.04). LVSI is an important prognostic variable in lymph node-negative stage IB and IIA cervical cancer. Although adjuvant pelvic radiotherapy may decrease the risk of recurrence in patients with LVSI, the majority of patients with negative lymph nodes may be treated with radical surgery alone.     

Is lymphadenectomy useful in the treatment of endometrial carcinoma?

In our institution endometrial carcinoma stages I and II is treated with uterovaginal brachytherapy and radical hysterectomy with pelvic lymphadenectomy. We have made a retrospective analysis of the results of lymphadenectomy to determine its place in the treatment strategy. Between 1976 and 1986, 155 patients were treated with these modalities (107 were stage I, 48 were stage II). The mean age was 60.2 years. Brachytherapy delivered 60 Gy, and then radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-six patients received pelvic external-beam irradiation because of lymph node involvement and or deep tumor invasion into the myometrium. Fourteen patients (9%) had lymph node involvement. External iliac lymph nodes were involved in 78.5% of these cases. The lymph node involvement rate was higher for patients with stage II disease, patients with grade 3 tumors, and patients in whom there was deep tumor invasion into the myometrium. Pelvic failure rate was 12% for node-negative patients and 36% for node-positive patients. The 5-year actuarial survival rates were 83% for node-negative and 41% for node-positive patients. We administer pelvic external-beam radiotherapy to all stage II patients, grade 2 or 3 patients, and patients in whom there is deep tumor invasion into the myometrium. We do not perform lymphadenectomy on these patients. We perform only external iliac sampling for patients with stage I, grade 1 tumor without deep tumor invasion.     

Recurrent cervical carcinoma after radical hysterectomy and pelvic lymph node dissection: a study of 32 cases

PURPOSE OF INVESTIGATION: To investigate the characteristics of patients with recurrent cervical carcinoma after radical hysterectomy and pelvic lymph node dissection (RHND), and to evaluate the effect of clinical and surgical pathologic factors on the outcome of these patients. METHODS: Data from the files of 32 patients with recurrent cervical carcinoma after RHND managed at the Soroka Medical Center from 1962 through 2005 were analyzed. RESULTS: These 32 patients represent a recurrence rate of 25.4%. The median recurrence-free interval was 19.3 (range, 1-106) months. The prevailing signs and symptoms were obstructive nephropathy, sacral pain and bowel obstruction. Sixteen (50%) patients had loco-regional recurrence alone, 12 (27.5%) loco-regional plus distant recurrence, and four (12.5%) distant recurrence alone. Treatment modalities included radiotherapy, chemotherapy and various surgical procedures. The 5-year survival rate was 35%, with 22 (68.7%) of the patients dead of disease at the end of follow-up. Univariate analysis demonstrated a significant worsening in survival with each of the following factors: loco-regional plus distant recurrence (p = 0.010), positive pelvic lymph nodes (p = 0.010), tumor size > or = 3 cm (p = 0.013), positive lymph vascular space involvement (p = 0.017) and RHND without bilateral salpingo-oophorectomy (p = 0.042). In a multivariate analysis, extent of recurrent disease (locoregional alone versus loco-regional plus distant recurrence) and pelvic lymph node status (negative vs positive) at RHND were the only significant predictors of survival. Uremia was the most common cause of death. CONCLUSIONS: Recurrent cervical carcinoma after RHND is a grave disease with unfavorable prognosis. In both univariate and multivariate analyses, extent of recurrent disease and pelvic lymph node status at RHND were significant predictors of survival.     

淋巴结转移的Ⅰb 1～Ⅱb期子宫颈癌患者手术后的综合治疗及预后分析

目的研究淋巴结转移的Ⅰb1～Ⅱb期宫颈癌患者广泛性子宫切除加盆腔淋巴结切除术后综合治疗的方式和预后。方法选取1990年1月至2003年6月复旦大学附属肿瘤医院接受手术治疗的Ⅰb1～Ⅱb期淋巴结转移的宫颈癌患者215例。所有患者均接受了广泛性子宫切除加盆腔淋巴结切除术。根据术后治疗情况将患者分为4组：放疗加化疗组（107例）、放疗组（45例）、化疗组（22例）和无辅助治疗组（41例）。通过比较4组患者的临床病理资料,对患者预后及可能影响预后的有关因素进行分析。结果放疗加化疗组、化疗组、放疗组和无辅助治疗组患者的3年无瘤生存率分别为60．7％、53．5％、47．4％和36．0％,放疗加化疗组患者的3年无瘤生存率显著高于无辅助治疗组,两组比较,差异有统计学意义（P=0．001）,而化疗组、放疗组的3年无瘤生存率分别与无辅助治疗组比较,差异无统计学意义（P值分别为0．060和0．159）。放疗加化疗组、化疗组、放疗组和无辅助治疗组患者的盆腔复发率分别为7．5％、22．7％、26．7％和34．1％,远处转移率分别为16．8％、18．2％、15．6％和22．0％,复发合并转移率分别为4．7％、0、4．4％和7．3％。放疗加化疗组盆腔复发率显著低于其余3组,与其余3组比较,差异有统计学意义（P〈0．01）,而远处转移率、复发合并转移率与其余3组比较,差异无统计学意义（P〉0．05）。多因素分析显示,肿瘤直径、病理类型、淋巴结转移数目和术后辅助治疗是影响淋巴结转移的宫颈癌患者预后的重要因素（P〈0．05）。结论淋巴结转移的宫颈癌患者根治性手术后辅助放、化疗能提高3年无瘤生存率,降低盆腔复发率。     

Histopathological factors influencing pelvic lymph node metastases in two or more sites in patients with cervical carcinoma undergoing radical hysterectomy.

BACKGROUND: Lymph node metastasis has been one of the strongest prognostic factors in patients with cervical cancer. In order to select patients with high risk for recurrence, a relationship between status of lymph node and other histopathological parameters was investigated in the patients treated with radical hysterectomy with pelvic lymph adnectomy. METHODS: Of 483 patients undergoing radical hysterectomy with pelvic lymph adnectomy, 309 had stage Ib disease, 62 stage IIa, and 112 stage IIb. RESULTS: Pelvic lymph node metastasis(PLNM) was positive in 98 patients (20%). Of those positive patients, 51(56%) had metastasis in one site, 25 (26%) in two sites, and 22 (22%) in three or more sites. There was a significant difference in survival between patients with metastasis in one or no sites and those in two or more sites (p<0.0001). There was a relationship between PLNM in more than two sites and histological parameters such as histologic subtype, longitudinal diameter of cervical lesion, degree of stromal invasion, depth of stromal invasion, lymph-vascular space invasion, parametrial invasion, and corpus invasion. All of these parameters except for histologic subtype were significantly correlated with the number of positive lymph node sites. Multivariate analysis revealed that among these parameters, longitudinal diameter of the cervical lesion, parametrial invasion, and lymph-vascular space invasion were independently significantly correlated with PLNM in two or more sites. CONCLUSIONS: From these results, patients having these three histopathological parameters could be considered as those with extensive disease distribution.     

Identifying local tumor variables for operable node-negative, margin-free patients with bulky cervical carcinoma of FIGO stage IB, IIA and IIB without adjuvant therapies

PURPOSE: To identify local risk factors for FIGO IB, IIA and IIB bulky cervical squamous cell carcinoma (tumor size > or = 4 cm) patients with node-negative, margin-free tumors treated by radical hysterectomy, pelvic lymph node and para-aortic lymph node dissections without adjuvant therapies. MATERIALS AND METHODS: Thirty-four patients were recruited between 1976 and 1989 because they all declined any postoperative adjuvant therapy. The pathology reports showed that all the specimen margins were free from cancer cells with no para-aortic or pelvic lymph node metastases. The survival interval was calculated starting from the time of surgical intervention to the time of death or the end of this study in the year 2000. RESULT: Tumor variables including cell differentiation, depth of stromal invasion, parametrial invasion, vaginal invasion, uterine body invasion, age, and FIGO stage were analyzed. Only vaginal invasion showed statistical significance for decreasing patient disease-free survival in both univariate and multivariate analyses with p values of 0.003 and 0.002, respectively. CONCLUSION: For node-negative and margin-free patients with bulky cervical squamous cell carcinoma with operable stage IB and IIB, surgical intervention alone could suffice when no vaginal invasion is noted plus an 85% survival rate could be achieved. A prospective pilot study should be initiated although this study showed an excellent survival rate which is perhaps due to the limited number of cases.     

Surgically-treated early cervical cancer: Prognostic factors and the significance of depth of tumor invasion

Hellebrekers BWJ, Zwinderman AH, Kenter GG, Peters AAW, Snijders-Keilholz A, Graziosi GCM, Fleuren GJ, Trimbos JB. Surgically-treated early cervical cancer: Prognostic factors and the significance of depth of tumor invasion. Int J Gynecol Cancer 1999; 9: 212–219.
The objectives of this study were to scrutinize surgical features and analyze local tumor parameters of early cervical cancer to identify patients at-risk for recurrent disease. Three hundred eight patients who underwent radical hysterectomy and pelvic lymphadenectomy between 1984 and 1997 were studied retrospectively. All radical hysterectomies were performed in a referral oncology center, and treatment policies and operating staff were the same during the study period. Operating time gradually decreased significantly during the study period from an average of 270 min to an average of 187 min ( P < 0.0001), and blood loss during surgery also decreased continually from 1515 ml to 1071 ml ( P < 0.0001). Postoperative radiation treatment was given to 119 patients (40%). The overall five-year survival rate was 83%, 91% for those with negative, and 53% for those with positive pelvic nodes. Univariate analysis showed that lymph node status, parametrial involvement, status of the surgical margins, capillary lymphatic space involvement, tumor size and depth of invasion were all significantly related to the occurrence of recurrent disease. Multivariate analysis revealed that lymph node involvement (hazard ratio 4.4), parametrial involvement, tumor size and depth of invasion were independent factors of prognostic significance for disease-free survival. It was concluded that the local control of cervical tumors infiltrating > 10 mm (hazard ratio 5.1) might be improved by adjuvant radiotherapy, even in the absence of lymph node metastasis, parametrial involvement or affected surgical margins.