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.     

Early invasive cervical cancer with pelvic lymph node involvement: to complete or not to complete radical hysterectomy?

The completion of radical hysterectomy in the face of pelvic lymph node involvement presents a dilemma for the surgeon. Some believe it is appropriate to abort the hysterectomy to avoid the excessive morbidity of combined treatment; others believe that completion of the hysterectomy enhances survival. This study was undertaken to define the impact of completing radical hysterectomy followed by adjuvant radiation therapy upon patient survival or pelvic control. Fifteen patients with stage IB and IIA invasive cervical cancer whose radical hysterectomies were aborted solely for reasons of pelvic lymph node involvement were compared to a control group of 15 patients matched for tumor size and number of lymph nodes involved whose radical hysterectomies were completed. Both groups were treated with radiation therapy postoperatively. Survival was not different between groups (P = 0.81). Unexpectedly, local control was slightly improved in the group treated by radiation only (P = 0.127). If radiation therapy is anticipated, completion of radical hysterectomy followed by radiation therapy appears to offer no advantage over radiation therapy with the uterus in place in patients with early-stage invasive cervical cancer and pelvic lymph node involvement.     

Chemotherapy versus radiotherapy versus observation for high-risk cervical carcinoma after radical hysterectomy: A randomized, prospective, multicenter trial.

BACKGROUND: Adjuvant treatment modalities after radical hysterectomy have long been used in an attempt to eradicate microscopic tumor residuals in patients at high risk for recurrence. However, it has not been clearly demonstrated that adjuvant radiation, adjuvant chemotherapy, or both improve the outcome. To evaluate the effect of adjuvant treatment in patients with high-risk cervical cancer after radical hysterectomy, the Austrian Gynecologic Oncology Group conducted a prospective, randomized, multicenter clinical trial between 1989 and 1995. MATERIAL AND METHODS: Seventy-six patients with stage IB-IIB cervical cancer treated with radical hysterectomy with pelvic lymph node metastases and/or vascular invasion randomly received adjuvant chemotherapy (400 mg/m2 carboplatin, and 30 mg bleomycin), standardized external pelvic radiation therapy, or no further treatment. RESULTS: After a median follow-up of 4.1 years (range, 2-7) there were no statistically significant differences (P = 0.9530) in disease-free survival among the three treatment arms. CONCLUSION: The data suggest that adjuvant chemotherapy or radiation do not improve survival or recurrence rates in high-risk cervical cancer patients after radical hysterectomy. The most important treatment for these patients seems to be radical abdominal hysterectomy with systematic pelvic lymphadenectomy.     

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.     

Radiation injury to intestine following hysterectomy and adjuvant radiotherapy for cervical cancer

OBJECTIVE: To evaluate the risk factors for nonrectal radiation-induced intestinal injury (NRRIII) following adjuvant radiotherapy (RT) for cervical cancer using a retrospective review of medical records. METHODS: From September 1992 to December 1998, 164 patients with uterine cervical cancer that had completed their allocated adjuvant radiotherapy at the Chinese Medical University Hospital were enrolled for NRRIII analysis. The patients were classified into two groups according to the extent of surgery. Group A consisted of 110 patients (International Federation of Gynecology and Obstetrics [FIGO] stage: IB, n = 87; IIA, n = 21; IIB, n = 2) undergoing radical hysterectomy and bilateral pelvic lymph node dissection, while Group B was composed of 54 analogs receiving adjuvant radiotherapy following incident extrafascial hysterectomy. Treatment consisted of external beam radiotherapy (EBRT) and high-dose-rate intravaginal brachytherapy (HDRIVB). Initially, the whole pelvis was treated with 10 MV X-rays. After irradiation (44 Gy in 22 fractions over 4-5 weeks), the field was limited to the true pelvis and a further 10-20 Gy delivered in 5-10 fractions. For 21 patients in group A without pelvic lymph node metastasis or lymphovascular invasion, the radiation field was confined to the lower pelvis, with a prescribed dose of 50-58 Gy delivered over 5-6 weeks. HDRIVB was performed using an Ir-192 remote after-loading technique at 1-week intervals. A total of 159 patients (97%) received two insertions, while 5 had only one. The standard prescribed HDRIVB dose was 7.5 Gy to the vaginal surface. Logistic regression analysis was performed for assessment of the factors associated with NRRIII. RESULTS: After 38-119 months of follow-up (median, 60), 22 patients (13.4%) developed Radiation Therapy Oncology Group (RTOG) grade 2 or greater NRRIII at a median latency of 18 months (range, 5-48). Four patients were diagnosed as grade 3 complications requiring surgery and three had expired. The independent factors for NRRIII were radical hysterectomy (P = 0.04, relative risk 2.45), lower-pelvic dose >54 Gy (P = 0.0001, relative risk 10.27), and age over 60 years (P = 0.001, relative risk 5.45). The incidence of NRRIII for patients receiving whole and lower-pelvic irradiation was 14.5% and 10.6%, respectively (P = 0.45). Although there was no statistical significance comparing the two external beam irradiation strategies in terms of NRRIII, all four patients with grade 3 NRRIII underwent whole pelvic irradiation. CONCLUSION: This study identifies three predictive factors for the development of NRRIII following adjuvant radiotherapy for cervical cancer. Limiting the EBRT dose to less than 54 Gy, meticulous patient selection in the elderly, careful planning of the irradiated field, and the constraint of vaginal brachytherapy are four approaches to optimization of postoperative adjuvant radiotherapy.     

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.     

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.     

Surgical pathologic factors in patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection: association with administration of adjuvant radiotherapy and effect on survival

PURPOSE OF INVESTIGATION: To identify surgical pathologic factors that best correlate with administration of adjuvant radiotherapy and best predict survival in 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: Fifty-four percent of the patients received postoperative adjuvant radiotherapy. In a univariate analysis, each of the following factors: positive pelvic lymph nodes, lower uterine segment involvement, lymph vascular space involvement, penetration > or = 50% of the cervical wall, grade 2+3, parametrial and/or paracervical involvement, vaginal margin involvement, non-squamous histologic type, tumor size > or = 3 cm and Stage IB2 + IIA was significantly associated with administration of radiotherapy. In a multivariate analysis, positiviy of pelvic lymph nodes was persistently the most significant factor associated with administration of radiotherapy. The 5-year survival rate was 82.6% overall. In a univariate analysis, a significant worsening in survival was demonstrated with positivity of pelvic lymph nodes and positivity of lymph vascular space involvement. In a "better fit" model of multivariate analysis, pelvic lymph node status was the strongest and the only significant predictor of survival. CONCLUSIONS: In patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection, pelvic lymph node status is the strongest factor affecting administration of adjuvant radiotherapy and the most significant predictor 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。     

Overall 5-year survival rate and prognostic factors in patients with stage IB and IIA cervical cancer treated by radical hysterectomy and pelvic lymph node dissection

Abstract. Kim SM, Choi HS, Byun JS. Overall 5-year survival rate and prognostic factors in patients with stage IB and IIA cervical cancer treated by radical hysterectomy and pelvic lymph node dissection.
The objective of this paper was to analyze the 5-year survival rate and prognostic factors for stage Ib and IIa cervical cancer treated by radical hysterectomy. A total of 366 patients with invasive cervical cancer treated by radical hysterectomy from June 1985 to June 1994 at Chonnam National University Hospital, Kwangju, Korea were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier estimator. Multivariate analysis was performed using the Cox proportional hazards regression model. The overall 5-year survival rate was 92% in stage Ib and 87% in stage IIa. Factors assessed for prognostic value included age, FIGO stage, cell type, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and pelvic lymph node metastases (LNM). In the multivariate analysis, age, cell type, and lymph node metastases were independent predictors of survival. Lower survival was associated with age greater than 50 years, adenocarcinoma, and presence of lymph node metastases. The higher survival rates in patients with single lymph node involvement or lymph node metastases below the level of the common iliac nodes (85 and 84.6%, respectively) versus multiple or extrapelvic lymph node metastases (50 and 20%, respectively) were statistically significant ( P < 0.01). In conclusion, patients who had lymph node metastases, adenocarcinoma, and were older than 50 years had a poorer survival rate. Such patients require more intense postoperative treatment and closer surveillance. Low-risk patients with a single lymph node metastasis below the level of the common iliac nodes may benefit from thorough lymphadenectomy without adjuvant therapy to prevent unpleasant complications.     

Isolated full-thickness cervical stromal invasion warrants post-hysterectomy pelvic radiotherapy in FIGO stages IB-IIA uterine cervical carcinoma

OBJECTIVE: To evaluate the potential benefit of postoperative radiotherapy (PORT) in women with isolated full-thickness cervical stromal invasion (FTSI) as an unfavorable pathological finding after radical hysterectomy and pelvic lymph node dissection (PLND) in FIGO stages IB-IIA cervical carcinoma. METHODS: A total of 1868 patients with stages IB-IIA cervical carcinoma underwent radical hysterectomy and PLND between January 1982 and December 2002. Seventy-four of these patients had isolated FTSI without any other unfavorable pathological finding, such as lymph node metastasis, microscopic parametrial involvement, involved resection margin, lympho-vascular space invasion, or large clinical tumor diameter (>4 cm). Forty-one of these patients had no adjuvant treatment (S group) and 33 received PORT (PORT group). Patients with isolated FTSI who received chemotherapy were excluded. Treatment outcomes in the PORT and S groups were compared. RESULTS: Ten-year disease-free survival (DFS) and pelvic-failure-free survival (PFFS) of S group vs. PORT group were 73.2% vs. 92.4% (P=0.038) and 79.8% vs. 97.0% (P=0.044), respectively. According to a Cox proportional hazards model developed by forward, stepwise regression incorporating all prognostic variables, only PORT was marginally significant for DFS (RR 0.234; 95% CI 0.051-1.067; P=0.061) and significant for PFFS (RR 0.055; 95% CI 0.005-0.620; P=0.019). A grade 4 late complication developed in two patients (6%) in PORT group. CONCLUSION: PORT administered to patients with isolated FTSI after radical hysterectomy and PLND improves pelvic control in FIGO stages IB-IIA cervical carcinoma with acceptable morbidity.     

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。     

Adjuvant radiotherapy following radical hysterectomy for patients with stage IB and IIA cervical cancer

From 1971 through 1984, 320 women underwent radical hysterectomy as primary therapy of stage IB and IIA cervical cancer. Two hundred forty-eight patients (78%) were treated with surgery alone and 72 patients (22%) received adjuvant postoperative external-beam radiotherapy. Presence of lymph node metastasis, large lesion (greater than 4 cm in diameter), histologic grade, race (noncaucasian), and age (greater than 40 years) were significant poor prognostic factors for the entire group of patients. Patients treated with surgery alone had a better disease-free survival than those who received combination therapy (P less than 0.001). However, patients receiving adjuvant radiation therapy had a higher incidence of lymphatic metastases, tumor involvement of the surgical margin, and large cervical lesions. Adjuvant pelvic radiation therapy did not improve the survival of patients with unilateral nodal metastases or those who had a large cervical lesion with free surgical margins and the absence of nodal involvement. Radiation therapy appears to reduce the incidence of pelvic recurrences. Unfortunately, 84% of patients who developed recurrent tumor after combination therapy had a component of distant failure. The incidence of severe gastrointestinal or genitourinary tract complications was not different in the two treatment groups. However, the incidence of lymphedema was increased in patients who received adjuvant radiation therapy. Although adjuvant radiation therapy appears to be tolerated without a significant increase in serious complications, the extent to which it may improve local control rates and survival in high-risk patients appears to be limited. In view of the high incidence of distant metastases in high-risk patients, consideration should be given to adjuvant systemic chemotherapy in addition to radiation therapy.     

Management of early-stage cervical carcinoma by modified (Type II) radical hysterectomy

OBJECTIVE:. Surgical management of cervical carcinoma by radical hysterectomy has been proven a highly effective method in treating early-stage disease. The purpose of this study was to evaluate the efficacy and safety of modified (Type II) radical hysterectomy for the treatment of early-stage (I-IIA) cervical carcinoma. METHODS: A retrospective analysis of data on 435 patients with cervical carcinoma who were managed by modified radical hysterectomy was performed. In 145 cases a multimodal approach was used due to the presence of one or more risk factors such as lymph node metastasis, CLS involvement, bulky tumor, and exocervical extension of disease. Preoperative irradiation was offered to 62 patients, whereas adjuvant irradiation was offered to 101 patients. RESULTS: The mean age of the patients was 42.5 years. The majority of the patients had squamous cell cancer (81.6%). The patients were clinically staged as IA (3.2%), IB (86.7%), and IIA (10.1%). Positive pelvic lymph nodes were noted in 65 patients (14.9%). Operative morbidity was minimal, whereas adjuvant radiation treatment had no impact on the disease but caused genitourinary morbidity in terms of ureteral stricture and postoperative bladder dysfunction (P < 0.001). The overall 5-year survival was 88.7%. The most significant predictors related to 5-year survival were nodal metastasis (P < 0.001), adenomatous histology (P < 0.001), lesion size (P < 0.001), and CLS involvement (P = 0.004). Adjuvant radiation resulted in better local pelvic control of the disease. CONCLUSION: The results of our study support the concept that less radical procedures could be effectively applied to early-stage cervical carcinoma 4 cm or smaller with optimal surgical margins.     

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.     

Primary malignant melanoma of the uterine cervix: case report and review of the literature.

This is a case report and review of the literature on primary melanoma of the cervix. There have been only 26 published cases of primary cervical melanoma and most are poorly documented and doubtful. The patients' ages ranged from 26 to 78 years old with a mean age of 55 +/- 13 years. The main presenting symptom was vaginal bleeding (83.0%). The majority of the patients, 88%, presented in stage I or II. Treatment varied from a simple excision of a cervical mass to a radical hysterectomy with lymph node dissection and adjuvant radiation or chemotherapy. Our patient presented with vaginal bleeding and was diagnosed as having stage IIa cervical melanoma. She underwent a radical hysterectomy, partial vaginectomy, and pelvic and paraaortic lymph node dissection. She received adjuvant radiation therapy and her survival was 29 months. The prognosis of primary cervical melanoma is usually poor and unpredictable. We recommend a radical hysterectomy and vaginectomy, if necessary, to obtain negative surgical margins of at least 2 cm. We advocate lymphadenectomy only for grossly positive nodes.     

Prognostic factors in stage IB-IIA cervical carcinomas treated with postoperative radiotherapy.

PURPOSE: This study investigated the prognostic significance of age, stage, tumor size, pelvic lymph node metastasis (PLM), surgical margin invasion, overall radiotherapy time (ORT), and interval between radiotherapy and surgery (IRS) in stage IB-IIA cervical carcinoma. METHOD AND MATERIALS: 100 patients treated with radical hysterectomy and postoperative radiotherapy were evaluated retrospectively. RESULTS: The 5-yr overall survival (OS), disease-free survival (DFS), and pelvic control rate (PC) were 83.6%, 82.8%, and 91.8%, respectively. PLM (p=0.008), IRS (p=0.01), ORT (p=0.007), and tumor size (p=0.028) were found to be significant on PC. PLM (p=0.04), ORT (p=0.04), and IRS (p=0.001) were significant on OS. PLM was significant (p=0.04) and IRS was marginally significant (p=0.06) on DFS. After multivariate analysis, PLM was significant on OS, DFS and PC. Recurrences were seen in 14 patients. CONCLUSION: According to this study PLM, IRS, and ORT are the most important prognostic factors. Recurrences outside the radiation volume leads to treatment failure.     

The case for completing the lymphadenectomy when positive lymph nodes are found during radical hysterectomy for cervical carcinoma

BACKGROUND: In the present study we report on the results of a retrospective study on the effect on survival of the pelvic lymphadenectomy in a group of 294 patients with stage Ia2-IIa cervical carcinoma treated by radical hysterectomy from 1984 through 1996 at the Leiden University Medical Center. METHODS: Lymphadenectomy was called 'complete' when lymph node bearing tissue had been removed from 5 or 6 lymph node stations and 'not-complete' when this was the case in 1-4 stations. RESULTS: A radical hysterectomy was carried out in 294 patients. In 63 patients positive lymph nodes were found. Patients with positive nodes showed poorer 5 year survival: 64.5% compared to 90% in patients with negative nodes. In the univariate analysis the following factors were found to affect the presence of node metastases in a statistically significant way: age, tumor size, depth of infiltration, vaso-invasion, surgical margins, parametrial infiltration, stage and place of referral. In 63 patients with positive nodes, a complete lymphadenectomy was carried out in 23 patients, and in 40 patients the procedure was incomplete. All 63 patients were treated by adjuvant radiation therapy; those with complete lymphadenectomy had significantly less recurrences (25%) compared to those with incomplete lymphadenectomy (56%): the relative risk (RR) was 2.9 (95% ci: 1.3-6.7), p=0.012. After adjustment for other prognostic factors including tumor size, depth of infiltration and parametrial involvement, the complete lymphadenectomy showed an independent effect on disease free survival: RR= 3.2 (95% ci: 1.3-7.7), p=0.011. Prognostic factors were not significantly different for patients with complete or incomplete lymphadenectomy. CONCLUSIONS: From the results of this study, although retrospective and non randomized, it can be concluded that to complete removal of lymph nodes in combination with radical hysterectomy seems to have a beneficial effect on prognosis in case of positive nodes. The policy of aborting the procedure when lymph node metastases are found in frozen section should be questioned.     

Radical hysterectomy followed by tailored postoperative therapy in the treatment of stage IB2 cervical cancer: feasibility and indications for adjuvant therapy

OBJECTIVE: To determine the outcome, complications and likelihood of requiring adjuvant therapy of patients with stage IB2 cervical cancer treated with primary radical hysterectomy and lymph node dissection. METHODS: Clinical and pathologic data between 1985 and 1999 were reviewed. Associations between clinical and pathologic variables were tested using the Fisher's exact test. Survival was estimated using the Kaplan-Meier method with significance being calculated using the Log Rank test. RESULTS: Six hundred radical hysterectomies were performed during the study period. Fifty-eight of these women (9.6% of all radical hysterectomies) were diagnosed with FIGO stage IB2 cancers. Sixteen patients (28%) had positive pelvic lymph nodes. Forty-six patients (79%) had invasion involving the outer 1/3 of the cervical stroma, six had positive vaginal margins while five had occult parametrial extension. After retrospective review of the histopathologic data from this case series, criteria from two recently published prospective multicenter Gynecologic Oncology Group (GOG) trials were applied to this data set. According to criteria established by GOG protocol 92, 30 (52%) patients should have theoretically received adjuvant pelvic radiation while 21 (36%) would have qualified for adjuvant chemotherapy and radiation according to the results of GOG protocol 109. In actual fact, only 35 patients (60%) received adjuvant radiotherapy and one received adjuvant chemo-radiation. Severe toxicity was unusual with two developing urinary fistulae and one having a pulmonary embolism. Despite the lack of adjuvant therapy in most cases, only 21 women (38%) recurred of whom 11 failed on the pelvic wall, with an estimated 5-year survival of 62.1%. CONCLUSIONS: Radical hysterectomy and tailored adjuvant radiation therapy in stage IB2 cervical cancer is feasible. Even without the liberal use of adjuvant therapy, survival in this high-risk group compares favorably to primary chemotherapy and radiation. According to recently published randomized clinical trials, most patients should receive adjuvant postoperative therapy. The benefits of this multimodality approach require randomized study.     

Invasive cervical cancer complicating intrauterine pregnancy: treatment with radical hysterectomy.

OBJECTIVE: Radical hysterectomy and bilateral pelvic lymph node dissection have become the mainstay of treatment for early-stage cervical cancer because of both a high success rate and acceptable morbidity. However, those cervical lesions that occur concomitant with an intrauterine pregnancy have historically been treated with irradiation. We report the morbidity and results of radical hysterectomy and bilateral pelvic lymph node dissection for the treatment of early-stage cervical cancer complicating intrauterine pregnancy. METHODS: Between 1955-1991, 13 patients were treated with radical hysterectomy and bilateral pelvic lymph node dissection with the fetus in situ, and eight others with cesarean delivery followed by radical hysterectomy and bilateral pelvic lymph node dissection. Charts were reviewed retrospectively. RESULTS: Mean operative time was 281 minutes. The mean blood loss was 777 mL with radical hysterectomy and bilateral pelvic lymph node dissection alone, and 1750 mL with cesarean delivery, radical hysterectomy, and bilateral pelvic lymph node dissection (P less than .01). Intraoperative morbidity included a single accidental cystotomy that was complicated in the postoperative period by a vesicovaginal fistula. Fever was the most common postoperative cause of morbidity (29%), while two patients (10%) had wound seromas and a single patient (5%) each had a pulmonary embolism, cystitis, and transfusion-related hepatitis. No perioperative deaths occurred. After documentation of maturity, seven healthy infants were delivered with no major morbidity. Twenty patients (95%) are alive and free of disease with a mean follow-up of 40 months. CONCLUSION: Radical surgery offers immediate treatment for early-stage cervical cancer during intrauterine pregnancy, with low associated morbidity, acceptable survival, and preservation of ovarian function.