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.     

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.     

Disease-free interval and recurrence pattern after the Okabayashi variant of Wertheim's radical hysterectomy for stage IB and IIA cervical carcinoma

From January 1982 to December 1991 271 patients underwent radical hysterectomy according to the Okabayashi modification for cervical carcinoma stage IB and IIA. Intraoperative complications occurred in 3.3%. The urinary fistula rate was only 2.2%. The 5-year Disease-free Interval (DFI) was 90%. In a univariate analysis tumor size 3 cm ( n = 99), positive pelvic nodes ( n = 53), adenocarcinoma ( n = 58) and parametrial involvement ( n = 36) were all associated with a significantly decreased DFI. Recurrence occurred in 27 patients (10%) of whom 22 died of disease. In adenocarcinoma, DFI was poor when positive pelvic nodes were present. In squamous cell carcinoma however, DFI was not influenced by pelvic node status. In patients with squamous cell carcinoma the locoregional recurrence rate was 3.4% when pelvic nodes were negative, whereas in those with positive nodes it was 5.8%. These data show that the Okabayashi modification of Wertheim's radical hysterectomy is a safe procedure resulting in very good locoregional tumor control, especially in patients with squamous cell cancer of the cervix.     

Criteria for elective irradiation of postoperative patients with stage 1b cervical cancer and radical hysterectomy without pelvic peritonealization

One hundred and sixty cases of cervical carcinoma have been treated surgically for the last 8 years. The numbers of cases of stage 0, 1a, 1b, 2a, 2b, 3 and 4 were 55, 14, 45, 15, 16, 10 and 1, respectively. Simple or extended hysterectomy without lymphadenectomy was performed for stage 0 and 1a cases, radical hysterectomy for stage 1b, 2a and 2b cases, and staging laparotomy for stage 3 and 4 cases. Before July, 1976, postoperative irradiation had been applied only for stage 1b, 2a, 2b cases with evidence of histological lymph node metastasis. Since two cases of vaginal stump recurrence were encountered during this period, irradiation was performed for all cases with a tumor size greater than 1cm in diameter, or with infiltration reaching half of the cervical wall thereafter. Three year comulative survival rates (3YCSR) for stage 0, 1a, 1b, 2a, 2b, 3a and 3b groups were 100%, 90%, 90.6%, 84.6%, 79.5%, 60% and 55.5%, respectively. In stage 1b group, there was a significant difference (p less than 0.05) in the 3YCSR between the cases with lymph node involvement (65.6%) and without it (96.2%). There was no significant difference in the factors indicating postoperative outcomes (the period for recovery of urinary functions, the incidence of ileus and the fever index) between the cases with and without pelvic peritonealization at the time of radical hysterectomy.     

Prognostic factors in node-positive patients with stage IB-IIB cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy.

OBJECTIVE: The purpose of the present study was to identify prognostic factors in surgically treated patients with stage IB-IIB cervical cancers, who also presented with positive pelvic nodes. METHOD: The patient population consisted of 68 individuals presenting with stage IB-IIB cervical cancers and with histologically proven pelvic lymph nodes. RESULT: We found no association between the type of adjuvant therapy and patient outcome. Multivariate analysis revealed that non-squamous histology was an independent prognostic factor for disease-free and overall survival rates. In squamous cell carcinomas, the bilateral nature of the positive nodes was found to be a significant factor for disease-free survival rates. In non-squamous cell carcinomas, positive nodes of more than 2 cm in size were found to be a significant factor for disease-free survival rates. CONCLUSION: Non-squamous histology was an independent prognostic factor and chemoradiotherapy did not improve the survival outcomes of the patients in this study population.     

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.     

Ovarian function after radical hysterectomy for stage IB carcinoma of cervix

Ovarian function was assessed in 20 patients after radical hysterectomy and lymph node dissection for Stage IB cervical carcinoma. All patients were under 45 years of age, and four were or had been on estrogen therapy for postmenopausal symptoms. The other 16 patients were free of symptoms and demonstrated premenopausal gonadotropin profiles. Fourteen of these 16 had luteal phase serum progesterone levels. Only one patient required reoperation for a pathologic condition of the adnexa. A surgical approach to Stage IB cervical carcinoma conserves ovarian function in 80% of patients.     

Selective radiation therapy in stage IB uterine cervical carcinoma following radical pelvic surgery

Thirty-five patients with squamous cell cancer of the cervix, Stage IB, treated by radical hysterectomy and bilateral pelvic lymph node dissection are analyzed for histopathologic factors including (1) depth of cervical stromal invasion, (2) degree of differentiation of the tumor, (3) vascular tumor invasion, and (4) lymph node involvement. The influence of these factors on the outcome is studied. A correlation is found in that the advanced depth of cervical stromal invasion appears to increase the risk of nodal involvement and also the subsequent recurrence in patients with negative nodes. The Grade 2 and Grade 3 disease is more often present in patients with outer one-third cervical stromal invasion, while the vascular tumorous invasion was only found in patients with middle and mostly with outer one-third cervical stromal invasion. A subgroup of patients is described, who are at high risk for recurrent disease following surgery and who may benefit from adjuvant radiation therapy.     

Oncologic outcome of fertility-sparing radical trachelectomy versus radical hysterectomy for stage IB1 cervical carcinoma

ObjectiveTo compare the oncologic outcomes of women who underwent a fertility-sparing radical trachelectomy (RT) to those who underwent a radical hysterectomy (RH) for stage IB1 cervical carcinoma.MethodsWe performed a case–control study of all patients with stage IB1 cervical carcinoma who underwent a vaginal or abdominal RT between 11/01 and 6/07. The control group consisted of patients with stage IB1 disease who underwent an RH between 11/91 and 6/07 and who would be considered candidates for fertility-sparing surgery. Information was extracted from a prospectively acquired database. Recurrence-free and disease-specific survival (RFS and DSS) were estimated using Kaplan–Meier estimates and compared with the log-rank test where indicated. Multivariate analysis was performed using the Cox regression method.ResultsForty stage IB1 patients underwent an RT and 110 patients underwent an RH. There were no statistical differences between the two groups for the following prognostic variables: histology, median number of lymph nodes removed, node positive rate, lymph-vascular space involvement (LVSI), or deep stromal invasion (DSI). The median follow-up for the entire group was 44 months. The 5-year RFS rate was 96% (for the RT group compared to 86% for the RH group (P = NS). On multivariate analysis in this group of stage IB1 lesions, tumor size < 2 cm was not an independent predictor of outcome, but both LVSI and DSI retained independent predictive value (P = 0.033 and 0.005, respectively).ConclusionFor selected patients with stage IB1 cervical cancer, fertility-sparing radical trachelectomy appears to have a similar oncologic outcome to radical hysterectomy. LVSI and DSI appear to be more valuable predictors of outcome than tumor diameter in this subgroup of patients.     

Postoperative extended-field irradiation in patients with pelvic and/or common iliac node metastases from cervical carcinoma stages IB to IIB

Radical hysterectomy with pelvic and common iliac lymphadenectomy was done for 207 Stage IB (148), IIA (19), and IIB (40) cervical carcinomas. Pelvic nodal involvement was limited in 30 (14.5%) cases, whereas common iliac nodes were involved in 16 (7.7%) cases. Common iliac node metastases were significantly increased, when the number of positive pelvic nodes increased from 2 to 3 or 4 or more (21.4% to 73.3%, P less than 0.05), when the tumor invaded deeper than 20 mm (3.7% to 22.2%, P less than 0.001), and when the tumor extended into parametrial tissues (4.8% to 14.8%, P less than 0.05). Postoperative extended-field irradiation was administered to 40 patients with nodal metastases. The 3-year disease-free rates were 85% in 24 patients with positive pelvic nodes, and 51% in 16 patients with common iliac node metastases; 70% in total. These results indicate that postoperative extended-field irradiation is essential for those patients with nodal metastases from locally resectable cervical carcinomas.     

Completed versus aborted radical hysterectomy for node-positive stage IB cervical cancer in the modern era of chemoradiation therapy

Objective

Debate continues about optimal management of patients with node-positive stage I cervical cancer. Our objective was to determine if patient outcomes are affected by radical hysterectomy in the modern era of adjuvant chemoradiation.

Methods

Cervical cancer patients diagnosed from 2000 to 2008 were identified. Demographics, therapy, clinicopathologic data, progression free survival (PFS), overall survival (OS), total radiation exposure, and grade 3-4 complications were analyzed by student t, Mann-Whitney, Fisher's exact, Kaplan-Meier, and log rank tests.

Results

This single-institution review evaluated forty-one of 334 (13.4%) patients scheduled to undergo radical hysterectomy that had gross nodal disease diagnosed intraoperatively. 15 underwent aborted radical hysterectomy following lymphadenectomy; the remaining 26 underwent radical hysterectomy and lymphadenectomy. Eleven patients undergoing radical hysterectomy underwent whole pelvic radiation therapy (WPRT) while 8 (30.7%) patients underwent WPRT and postoperative vaginal brachytherapy (BT) for local treatment secondary to close margins. All patients undergoing aborted radical hysterectomy underwent WPRT and BT. With mean follow-up of 42.3 months, there were no significant differences in urinary, gastrointestinal, or hematologic complications between groups. When comparing those undergoing radical hysterectomy to aborted radical hysterectomy, there were no significant differences in local recurrence (11.5% vs 26.7%, p = 0.39) or distant recurrence (19.2% vs. 33.3%, p = 0.45), PFS (74.9 months vs 46.8 months, p = 0.106), or OS (91.8 months vs 69.4 months, p = 0.886).

Conclusions

Treatment of patients with early stage cervical cancer and nodal metastasis may be tailored intraoperatively. Completion of radical hysterectomy and lymphadenectomy decreases radiation exposure without apparently compromising safety or outcome in the era of adjuvant chemoradiation.     

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.     

Treatment of stage IB2, IIA bulky cervical cancer: a single-institution experience of neoadjuvant chemotherapy followed by radical hysterectomy and primary radical hysterectomy

Introduction  

The aim of this study was to compare the efficacy and safety of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy (NAC group) with primary radical hysterectomy (RH group).     

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.     

Radical hysterectomy and pelvic lymphadenectomy for stage IB2 cervical cancer

OBJECTIVE: We wished to evaluate survival and adverse outcomes of patients with stage IB2 cervical cancer treated primarily with radical hysterectomy and lymphadenectomy. METHODS: A review was performed of all patients undergoing primary radical hysterectomy for stage IB2 cervical cancer at two institutions from 1987 to 2002. Patients were stratified into low, intermediate (Gynecologic Oncology Group protocol 92 criteria), and high-risk (positive nodes, margins, or parametria) groups. Survival and progression-free interval were analyzed using the Kaplan-Meier method and multivariate analysis. RESULTS: Seventy-two patients underwent primary type III radical hysterectomy and lymphadenectomy (72 pelvic, 58 pelvic and paraaortic). Patients were classified as low (n = 6), intermediate (n = 49), or high (n = 17) risk for recurrence. Adjuvant therapy was administered to 94%, 12%, and 0% of the high-, intermediate-, and low-risk groups, respectively. Five-year survival was 72%, while 5-year progression-free survival was 63%. Five-year overall and progression-free survival by risk group were 47% and 40% (high-risk), 80% and 66% (intermediate-risk), 100% and 100% (low-risk). Predictors of survival in multivariate analysis were Caucasian race (P = 0.001), older age (P = 0.017), inner 2/3 cervical wall invasion (P = 0.045), and absence of lymph-vascular invasion (P < 0.001). Major complications were experienced by 10/72 (13.9%) patients. Among 34 patients who received radiation therapy, two (5.9%) experienced complications attributable to radiation. CONCLUSIONS: Radical hysterectomy and lymphadenectomy followed by tailored adjuvant therapy is a reasonable alternative to primary radiotherapy for stage IB2 cervical cancer. Patients with low- and intermediate-risk factors have satisfactory results after primary surgical management. A prospective randomized trial will clarify the optimal mode of initial therapy for patients with stage IB2 disease.     

The prognostic significance of the minimum thickness of uninvolved cervix in patients with cervical carcinoma stages IB, IIA, and IIB

The minimum thicknesses of uninvolved cervical tissues at the sites of deepest tumor invasion were evaluated in 899 patients with Stage IB, IIA, and IIB cervical carcinoma. Minimum thicknesses were greater than or equal to 10 mm in 126 (14%), 5-10 mm in 247 (27%), and less than 5 mm in 335 (38%) patients. Parametrial extension was found in 191 (21%) patients. Nodal metastasis rates were 6, 10, 22, and 55%, respectively. Patients with greater than or equal to 10-mm thicknesses did not have two or more positive nodes (P less than 0.05). The proportion of patients with two or three positive nodes increased from 3 to 10% (P less than 0.005) as the minimum thickness decreased from 5-10 to less than 5mm. The proportion of patients with four or more positive nodes increased from 3 to 22% (P less than 0.001) in cases in which tumor invaded the parametrial tissues. Five-year disease-free rates were 99, 93, 88, and 65%, respectively. Each percentage decrease was significant (P less than 0.05, 0.05 less than P less than 0.01, and P less than 0.001). These results indicate that uninvolved cervical thickness is a good indicator of nodal metastases, number of positive nodes, and patient prognosis.