Radical hysterectomy with adjuvant radiotherapy versus definitive radiotherapy alone for FIGO stage IIB cervical cancer

Objectives

The aim of this study was to compare the treatment outcomes and adverse effects of radical hysterectomy followed by adjuvant radiotherapy with definitive radiotherapy alone in patients with FIGO stage IIB cervical cancer.

Methods

We retrospectively reviewed the medical records of FIGO stage IIB cervical cancer patients who were treated between April 1996 and December 2009. During the study period, 95 patients were treated with radical hysterectomy, all of which received adjuvant radiotherapy (surgery-based group). In addition, 94 patients received definitive radiotherapy alone (RT-based group). The recurrence rate, progression-free survival (PFS), overall survival (OS), and treatment-related complications were compared between the two groups.

Results

Radical hysterectomy followed by adjuvant radiotherapy resulted in comparable recurrence (44.2% versus 41.5%, p = 0.77), PFS (log-rank, p = 0.57), and OS rates (log-rank, p = 0.41) to definitive radiotherapy alone. The frequencies of acute grade 3–4 toxicities were similar between the two groups (24.2% versus 24.5%, p = 1.0), whereas the frequencies of grade 3–4 late toxicities were significantly higher in the surgery-based group than in the RT-based group (24.1% versus 10.6%, p = 0.048). Cox multivariate analyses demonstrated that treatment with surgery followed by adjuvant radiotherapy was associated with an increased risk of grade 3–4 late toxicities, although the statistical significance of the difference was marginal (odds ratio 2.41, 95%CI 0.97–5.99, p = 0.059).

Conclusions

Definitive radiotherapy was found to be a safer approach than radical hysterectomy followed by postoperative radiotherapy with less treatment-related complications and comparable survival outcomes in patients with FIGO stage IIB cervical cancer.     

Treatment of cervical cancer with adjuvant chemotherapy versus adjuvant radiotherapy after radical hysterectomy and systematic lymphadenectomy

Aim:  To compare the clinical efficacy focused on post-treatment morbidity between adjuvant chemotherapy (CT) and pelvic radiotherapy (RT) after radical hysterectomy for patients with cervical cancer.
Methods:  A total of 125 patients with cervical squamous cell carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy at Hokkaido University Hospital between 1991 and 2002 were enrolled in the study for retrospective analysis. Seventy patients with recurrent risk factors, including deep stromal invasion, lymph vascular space invasion, parametrial invasion, lymph node metastasis (LNM), and bulky tumor (≥4 cm), received adjuvant therapy; 42 were treated with RT, and 28 were treated with CT. Almost all patients with multiple LNM received RT. Analyses were also performed on a subgroup of 50 patients without multiple LNM (23 RT, 27 CT). Clinical efficacy of post-treatment morbidity and survival was evaluated.
Results:  Because there were more patients with multiple LNM in the RT group, we analyzed disease-free survival in 50 patients without multiple LNM. The 3-year disease-free survival rate was 82.6% with RT and 96.3% with CT ( P  = 0.16). Postoperative bowel obstruction was significantly more frequent in the RT group versus the CT ( P  = 0.007) and no-therapy ( P  = 0.0026) groups. Urinary disturbance was also more frequent in the RT group than in the CT ( P  = 0.0016) and no-therapy ( P  = 0.089) groups.
Conclusion:  CT has the equivalent therapeutic effect as RT with fewer postoperative complications for patients with intermediate risks. A prospective randomized trial is needed to compare CT combined with radical hysterectomy and pelvic lymphadenectomy to RT or chemoradiotherapy.     

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.     

Early stage cervical cancer with negative pelvic lymph nodes: pattern of failure and complication following radical hysterectomy and adjuvant radiotherapy

PURPOSE OF INVESTIGATION: The objective was to optimize the adjuvant treatment for patients with lymph node negative cervical cancer by analyzing patterns of failure and complications following radical hysterectomy and adjuvant radiotherapy. METHODS: From September 1992 to December 1998, 67 patients with lymph node negative uterine cervical cancer (FIGO stage distribution: 50 Ib. 17 IIa), who had undergone radical hysterectomy and postoperative adjuvant radiotherapy with a minimum of three years of follow-up were evaluated. All patients received 50-58 Gy of external radiation to the lower pelvis followed by two sessions of intravaginal brachytherapy with a prescribed dose of 7.5 Gy to the vaginal mucosa. For 21 patients with lymphovascular invasion, the initial irradiation field included the whole pelvis for 44 Gy. The data were analyzed for actuarial survival (AS), pelvic relapse-free survival (PRFS), distant metastasis-free survival (DMFS), and treatment-related complications. Multivariate analysis was performed to assess the prognostic factors. RESULTS: The respective five-year AS, PRFS, and DMFS for the 67 patients were 79%, 93% and 87%. Multivariate analysis identified two prognostic factors for AS: bulky tumor vs non-bulky tumor (p = 0.003), positive resection margin (p = 0.03). The independent prognostic factors for DMFS was bulky tumor (p = 0.003), while lymphatic permeation showed marginal impact to DMFS (p = 0.08). The incidence of RTOG grade 1-4 rectal and non-rectal gastrointestinal complication rates were 20.9% and 19.4%, respectively. The independent prognostic factor for gastrointestinal complication was age over 60 years (p = 0.047, relative risk 4.1, 95% CI 1.2 approximately 11.7). The incidence of non-rectal gastrointestinal injury for the patients receiving whole pelvic radiation and lower pelvic radiation was 28.5% and 15.2%, respectively (p = 0.25). CONCLUSION: For patients with lymph node negative cervical cancer following radical hysterectomy, adjuvant lower pelvic radiation appears to be effective for pelvic control. It is also imperative to intensify the strategies of adjuvant therapy for some subgroups of patients.     

Urodynamics following radical abdominal hysterectomy for cervical cancer

Summary We performed urologic evaluations and urodynamic studies on 40 patients before and 2 weeks, 6 months and 1 year after radical abdominal hysterectomy for cervical cancer. Preoperative findings were mostly within normal limits. Fourteen days after surgery, all patients had small, spastic bladders and 68% had residual urine. Bladder sensation was impaired in all patients at 2 weeks and in 63% after 1 year. The average bladder capacity was 400 ml before surgery, 180 ml at 2 weeks, 350 ml at 6 months, and 460 ml at 1 year. One year postoperatively, no patient had residual urine, but 17.5% had asymptomatic bacteriuria, 17.5% had bladder trabeculation, 62.5% had abnormal compliance, and 85% used abdominal straining to void. Three patients developed overflow incontinence and 8 women developed urodynamic stress incontinence. Most patients were tolerant of the observed dysfunction.     

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.     

Radical hysterectomy for recurrent cervical cancer following radiation therapy

In patients with small central recurrences following radiation therapy for cervical cancer the surgeon may have to make a judgment as to when radical hysterectomy is preferable to exenteration. During the years 1968-1984 there were 21 radical hysterectomies performed at Memorial Sloan-Kettering Cancer Center for recurrent cervical cancer. The original clinical stage distribution is as follows: IB-4, IIA-4, IIB-11, IIIB-1, IVA-1. The median interval from initial diagnosis to recurrence was 10 months. There were two operative deaths; both were from sepsis. Ten of the 21 patients developed postoperative fistulas, with 9 requiring surgical diversion of the urinary or both urinary and intestinal tracts. Thirteen of 21 patients (62%) have survived with a median follow-up of 73 months. Seven patients suffered recurrences following radical hysterectomy. All developed recurrence in the central pelvis. Four had sidewall disease as well, but none had distant disease at the time recurrence was diagnosed. Of 11 patients with cervical tumors of 2 cm or less in size at the time of radical hysterectomy, none experienced recurrence, while among 10 patients with tumor size of greater than 2 cm, 7 had recurrence. All patients whose initial clinical stage was IB or IIA have survived without recurrence. There was only 1 survivor among 5 patients with positive parametrial or vaginal margins. Six of the 13 survivors required urinary diversion, and 2 required colostomy as well. Radical hysterectomy for this indication is a morbid procedure which should be undertaken only by the most experienced of pelvic surgeons and limited to patients of early clinical stage with central recurrences of less than 2 cm in size.     

Self-assessment of morbidity following radical hysterectomy for cervical cancer.

The aim of this study was to assess the magnitude of the morbidity following radical surgery for early stage cervical cancer. We performed a retrospective survey of all women who had undergone a radical hysterectomy and lymphadenectomy between the months of July 1995 and December 1996 inclusive at either the Royal Marsden or St George's Hospital (n =38), using a detailed questionnaire on bladder, ano-rectal and sexual function, both before and after treatment. Sixteen women (44.4%) received adjuvant radiotherapy. The mean interval between surgery and inquiry was 16.4% months (range 8-25 months). The mean age at the time of surgery was 40.5 years. Thirty-six out of 38 women contacted responded (94.7%). Overall 33 women (91.7%) reported new bladder, ano-rectal or sexual symptoms. Complaints of urinary incontinence, particularly of urge incontinence, and of voiding difficulties increased significantly after surgery (P <0.05). However, only 5.3% of women had sought treatment. Tenesmus increased significantly (P <0.05), while increases in diarrhoea and faecal incontinence were not statistically significant (P =0.051). Although 12.9% of women stated an improvement in their sex lives, 54.8% thought that their sex life was worse after treatment, and 12.9% of women had ceased sexual activity altogether. Of women of childbearing age 53.8% felt adversely affected by their loss of fertility. Bladder, ano-rectal and sexual symptoms are very common following radical hysterectomy for cervical cancer, with adverse effect on quality of life, and persist into the second year after treatment.     

Urological complications after radical hysterectomy with or without radiotherapy for cervical cancer

Summary We reviewed urologic complications in 320 patients who underwent radical abdominal hysterectomy for stage Ib–IIb cervical cancer. 145 patients received adjuvant radiotherapy, and 116 were available for urodynamic testing 1–14 years later. The overall incidence of fistulas was 4.4%. Three of eight fistulas following surgery alone healed spontaneously; all fistulas following adjuvant radiotherapy required surgical correction. Nocturia and urgency were reported more often after adjuvant radiotherapy than after surgery alone. We conclude that urologic complications after radical hysterectomy can be made more intractable by adjuvant radiotherapy.     

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.     

Radical hysterectomy for recurrent or persistent cervical cancer following radiation therapy

Abstract. Maneo A, Landoni F, Cormio G, Colombo A, Mangioni C. Radical hysterectomy for recurrent or persistent cervical cancer following radiation therapy.
The objective of this paper was to determine the role of radical hysterectomy in persistent or recurrent cervical cancer after primary radiation therapy.
Between 1982 and 1995, 34 patients underwent radical hysterectomy for persistent ( n = 15) or recurrent ( n = 19) cervical cancer after primary radiotherapy. Univariate analysis using log-rank comparison of survival curves was conducted to identify clinical and pathologic factors predictive of survival. The median tumor size at the time of recurrence or persistence was 3.2 cm (range 1–6 cm). 24 patients (70%) had recurrence limited to the uterine cervix; four (12%) had vaginal involvement and six (18%) had early parametrial involvement. No treatment-related deaths were observed. Eighteen major complications (grade III-IV) occurred in 15 cases (44%); 5 patients experienced a fistula. Mean follow-up time was 81 months (range 33–192 months). Recurrent disease was documented in 20 patients (59%), and median time to recurrence was 37 months (range 4–56 months). Fifteen patients (44%) are alive without evidence of disease at a median survival of 81 months (range 33–192), and 18 patients (53%) died of disease with a median survival of 22 months (range 7–106). One patient died of intercurrent disease. Actuarial 5-year survival rate for the whole group is 49%. Patients with FIGO stage IB-IIA at primary diagnosis, no clinical parametrial involvement, and small (≤ 4 cm) tumor diameter at the time of recurrence show a good prognosis (11/17 alive NED) compared to patients who do not fit the above mentioned criteria (4/17 NED, P = 0.01). We conclude that radical hysterectomy can be offered as an alternative procedure to exenteration only in highly selected patients.     

Treatment results of adjuvant chemotherapy after radical hysterectomy for intermediate- and high-risk stage IB-IIA cervical cancer

OBJECTIVE: To determine the effectiveness of chemotherapy alone as postoperative adjuvant therapy for intermediate- and high-risk cervical cancer. METHODS: The study group comprised of 65 consecutive patients with stage IB or IIA squamous cell or adenosquamous cervical cancer who were initially treated with radical hysterectomy and pelvic lymphadenectomy between 1993 and 2002. Tumors were of intermediate-risk (stromal invasion > 50%, n = 30) or high-risk (positive surgical margin, parametrial invasion, and/or lymph node involvement, n = 35). In all cases, chemotherapy was administered adjuvantly: three courses of bleomycin, vincristine, mitomycin, and cisplatin for intermediate-risk cases and five courses for high-risk cases. Disease-free survival and complications of the combined therapy were investigated. RESULTS: Estimated 5-year disease-free survival was 93.3% for the 30 patients with intermediate-risk tumors (100% for those with squamous cell carcinoma and 71.4% for those with adenosquamous carcinoma) and 85.7% for the 35 patients with high-risk tumors (89.3% for those with squamous cell carcinoma and 71.4% for those with adenosquamous carcinoma). The incidence of locoregional recurrence was 3.3% in the intermediate-risk group and 8.6% in the high-risk group. Side effects of chemotherapy and complications of the combined therapy were within acceptable limits. No patient had severe bleomycin-related pulmonary toxicity. Only 1.5% of patients developed small bowel obstruction, which was cured by conservative therapy. CONCLUSIONS: The treatment results suggest the potential role of adjuvant chemotherapy alone for patients with cervical cancer.     

Chemoradiation with adjuvant hysterectomy for stage IB-2 cervical cancer: a 10-year experience

To review outcomes of patients with stage IB-2 cervical carcinoma treated with chemoradiation therapy (CRT) followed by total abdominal hysterectomy (TAH), common iliac and para-aortic lymphadenectomy (PAL). A retrospective review of patients with stage IB-2 cervical cancer treated with CRT followed by TAH/PAL from 1999 to 2009 was performed. Brachytherapy was limited to 1,500–1,800?cGy. Sixty-nine patients were identified. The mean age was 46.7?years, tumor diameter 5.4?cm, and all patients had complete clinical response to CRT. The mean follow-up was 61.7?months. There were no central pelvic relapses and two pelvic sidewall failures (97% pelvic control). The mean time to progression was 31.6?months, and 5-year disease-specific survival was 81%. Three (4.3%) patients developed symptomatic vaginal stenosis. CRT plus adjuvant hysterectomy for stage IB-2 cervical cancer resulted in excellent pelvic control and 5-year survival. Vaginal stenosis was rare.     

Small intestine injury in laparoscopic-assisted vaginal hysterectomy

STUDY OBJECTIVE: To review laparoscopic-assisted vaginal hysterectomy (LAVH) cases for instances of small intestine injury. DESIGN: Retrospective review (Canadian Task Force Classification II-2). SETTING: Tertiary care university hospital. PATIENTS: Two thousand six hundred eighty-two women. INTERVENTION: LAVH. MEASUREMENTS AND MAIN RESULTS: Indications for hysterectomy were myomata uteri, adenomyosis, intractable menorrhagia, endometriosis, severe pelvic adhesions, cervical intraepithelial neoplasia, endometrial polyps, and hyperplasia. Small bowel injuries occurred in five women (1.9/1000), one (20%) of which was recognized postoperatively. Thermal injuries occurred in two patients, trocar injuries in two, and a dissection wound in one. Two-layer closure was performed for three patients, and partial resection with reanastomosis for two. All patients were discharged without sequelae. CONCLUSION: Small bowel injury during LAVH is not common. It may have unusual characteristics and devastating consequences if not recognized and treated promptly.     

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.