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 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.     

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.     

腹腔镜广泛子宫切除和盆腔淋巴结切除术治疗子宫颈癌237例临床分析

目的探讨腹腔镜广泛子宫切除术治疗子宫颈癌的可行性、安全性、临床疗效、并发症和远期生存率。方法收集第三军医大学西南医院2000年9月至2006年7月期间,施行腹腔镜下广泛子宫切除术加盆腔淋巴结切除术治疗Ⅰa～Ⅱb期的子宫颈癌患者237例,并对其临床资料和随访情况进行回顾性分析。结果腹腔镜平均手术时间（209．7±53．8）min,术中平均出血量（316．5±174．4）ml,术后肠道功能恢复时间为（2．5±0．6）d。术后近期并发症：输尿管阴道瘘5例,膀胱阴道瘘3例,输尿管狭窄2例,深静脉栓塞9例,淋巴囊肿4例,1例腹壁切口处转移;远期并发症：膀胱功能障碍47例,直肠功能障碍56例。复发率8．4％,转移率7．6％,死亡率13．5％。患者总体1年、3年和5年生存率分别是95．6％、86．90和80．4％,中位生存期为76个月。结论腹腔镜广泛子宫切除加盆腔淋巴结切除术治疗宫颈癌是安全、可行的,远期疗效良好,可以作为子宫颈癌手术治疗的选择方式之一。     

子宫颈癌放射治疗的规范化

子宫颈癌是影响中国女性健康的重大疾病.随着对该疾病认识的加深,以手术、放疗、化疗相结合的综合治疗模式日趋成熟.文章根据子宫颈癌发展的不同阶段,系统阐述了放射治疗在子宫颈癌治疗中的应用和价值,以期为临床决策提供参考.     

Sexual dysfunction in Thai women with early-stage cervical cancer after radical hysterectomy

We determined the prevalence of sexual dysfunction in women with early-stage cervical cancer who had undergone radical hysterectomy in three institutions of Thailand. An interview was conducted according to the structured questionnaire composing of seven domains of sexual function: frequency, desire, arousal, lubrication, orgasm, satisfaction, and dyspareunia. From 105 women included in the study, mean age was 45.3 +/- 7.8 years. Seventy-five (71.4%) were in premenopausal period. Eight out of 105 women (7.6%) never resumed their sexual intercourse after radical hysterectomy, 97 women resumed their sexual intercourse during 1-36 months postoperation (median, 4 months). Dyspareunia was increased in approximately 37% of women, while the other six domains of sexual function were decreased, ranging from approximately 40-60%. Of interest, only 10.5% of these cervical cancer women had some information of sexual function from medical or paramedical personnel, 17.1% obtained it from other laymen or public media, and 61.9% had never had it from any resources. Our conclusion is-sexual dysfunction is a common problem after cervical cancer treatment, but it has not been well aware of. These findings may necessitate health care providers to be more considerate on this problem.     

同步放化疗与放疗对早期子宫颈癌手术患者生存率的影响

目的评价同步放化疗与放疗对早期宫颈癌手术患者生存率的影响。方法检索公开发表的比较早期宫颈癌患者同步放化疗与放疗对生存率影响的临床研究文献,对其按meta分析的要求进行质量评估,并采用Stata 9.0软件进行统计学分析。结果共8篇文献符合纳入标准,总样本量1535例,其中同步放化疗组812例,死亡146例;放疗组723例,死亡222例。采用固定效应模型合并效应量,相对危险度(RR)=0.64(95%CI:0.53～0.78)。亚组分析显示,术前或术后同步放化疗对生存率影响比较,差异无统计学意义(P>0.05)。敏感性分析显示,本研究结果真实可靠。结论与放疗相比,同步放化疗能够显著改善早期宫颈癌手术患者的生存率。     

Neoadjuvant chemotherapy followed by radical hysterectomy for invasive cervical cancer diagnosed during pregnancy: report of a case and review of the literature

Although cervical carcinoma is among the most frequently encountered malignancies during pregnancy, only four cases of neoadjuvant chemotherapy during pregnancy have been reported. A 28-year-old A0P1G2M0 was diagnosed at 15 weeks with stage Ib1 invasive squamous cervical cancer. Because she strongly desired the continuation of this pregnancy, after extensive counseling she was treated with 75 mg/m(2) cisplatin every 10 days starting at 17 weeks. After six cycles, clinically and radiologically stable disease with normalization of the squamous cell carcinoma tumor marker was obtained. An elective cesarean delivery followed by radical hysterectomy and lymphadenectomy was performed at 32 weeks gestation. The pathology report revealed a moderately differentiated squamous cell carcinoma of 3.5 cm, and all 33 lymph nodes were free of disease. Neonatal examination of the baby could not reveal any abnormalities, and this was confirmed at 6 months. The use of neoadjuvant chemotherapy enabled us to continue this pregnancy until the fetus was viable. Cisplatin did not influence the short-term outcome, but only a long-term follow-up will inform us on its safety during pregnancy.     

A randomized trial comparing platinum-based chemotherapy followed by radiotherapy vs. radiotherapy alone in patients with locally advanced cervical cancer

Seventy-one patients with stage IIb-IVa cervical cancer were entered on a randomized trial comparing standard pelvic radiotherapy vs. 3 cycles of combination chemotherapy with cisplatin, vinblastine and bleomycin followed by pelvic radiotherapy. Four out of 34 patients randomized to PVB followed by radiotherapy received no PVB and a further 3 patients had only one or 2 cycles of chemotherapy prior to radiotherapy due to drug-related toxicity or progressive disease. After a median follow-up of 3.1 years, no significant difference in survival has emerged between the two randomized groups. However, a difference in the pattern of relapse is emerging with a relatively reduced frequency of systemic relapse in patients receiving chemotherapy prior to local radiotherapy compared to radiotherapy alone. Tumor response was seen following PVB treatment and prior to radiotherapy in 47% of patients. Overall the tumor response rate following completion of radiotherapy was 89% in those treated by radiotherapy and 94% after PVB+radiotherapy. Thirty-three percent of patients randomized to radiotherapy alone relapsed first at a distant (extra pelvic site), and only 18% of patients randomized to initial PVB followed by radiotherapy relapsed systemically initially. When results are presented according to treatment actually given, these trends in patterns of treatment failure are magnified. No treatment-related deaths were reported, and there was no excess of complications with pelvic radiotherapy in the group who had received prior PVB chemotherapy.     

Neoadjuvant chemotherapy followed by robotic radical hysterectomy in locally advanced cervical cancer: A multi-institution study

Objective

Minimally invasive surgery has been performed in locally advanced cervical cancer (LACC) without adverse effect in patient's overall prognosis and survival. The aim of this report is to evaluate the feasibility and morbidity of total robotic radical hysterectomy (TRRH) with pelvic lymphadenectomy in patients with LACC after neo-adjuvant chemotherapy (NACT).

Methods

From February 2008 to April 2013 a retrospective data collection of women undergoing TRRH for cervical cancer stage FIGO IB2 to IIB, after neo-adjuvant chemotherapy, was conducted at “Regina Elena” National Cancer Institute of Rome and European Institute of Oncology of Milan. All patients deemed operable underwent TRRH with pelvic lymphadenectomy within 4 weeks from the last chemotherapy cycle.

Results

Median operative time was 225 min (range, 105–387 min). The median blood loss was 150 mL (range, 30–700 mL). The median number of removed pelvic lymph nodes was 23 (range, 8–69). Sixteen patients had an optimal response (12 PCR, 4 pPR1) to chemotherapy, 33 patients had a pPR2 and 11 patient showed stable disease. Adjuvant therapy was administrated in 36 patients (60%). We experienced one intra-operative complication and 19 post-operative complications, but no conversions to laparotomy were necessary to manage these complications. Six patients received a blood transfusion. At the time of this report, with a median follow-up of 28.9 months, 50 patients (83%) are free from recurrence.

Conclusion

This experience demonstrates the feasibility of TRRH pelvic lymphadenectomy after NACT in LACC with good accuracy and safety.     

Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy in locally advanced cervical cancer

Objectives

To evaluate the efficacy, in terms of safety, overall survival and progression free survival of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemotherapy in patients affected by locally advanced cervical cancer (stage IB2-IIB) with or without node metastases.

Methods

Between June 2000 and February 2007, all patients with diagnosis of locally advanced cervical cancer referred to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome were eligible for this protocol. All enrolled patients received 3 cycles of platinum-based chemotherapy every 3 weeks according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq. After neoadjuvant chemotherapy all patients with stable or progressive disease were excluded from the protocol, the others were submitted to classical radical hysterectomy, bilateral salpingo-oophorectomy and bilateral systematic pelvic lymphadenectomy and 4 cycles of adjuvant treatment with platinum based chemotherapy were executed.

Results

Concerning intention to treat basis analysis, 5 year overall survival (OS) and disease-free survival (DFS) are 77% and 61%, respectively. The 5-year OS of patients with positive pelvic nodes and those with negative nodes metastases was respectively 60% and 87%. Concerning the according to protocol analysis, the 5-year OS and DFS are 81% and 70% respectively. The 5-year OS in patient with positive and negative lymph nodes is 75% and 88% respectively.

Conclusions

The adjuvant chemotherapy regimen after neoadjuvant chemotherapy and radical surgery represents a valid treatment for patients with locally advanced cervical cancer.     

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.     

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.