A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: preliminary results

OBJECTIVE: Concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. This study was a preliminary result of a randomized two arms, prospective, open-label phase III trial comparing the activity and safety of the concurrent chemoradiation of Tegafur-Uracil and carboplatin or carboplatin alone in locally advanced cervical cancer. MATERIALS AND METHODS: The stage IIB-IIIB cervical cancer patients were randomized to have Tegafur-Uracil 225 mg/m(2)/day orally, 5 days a week and carboplatin 100 mg/m(2) IV over 30-60 min, weekly on day 1 concurrent with standard radiotherapy (Group A) or carboplatin alone concurrent with standard radiotherapy (Group B). RESULTS: Four hundred and sixty-nine patients were randomized to Group A (n=234) or Group B (n=235). The tumor response at 3-month follow-up time showed no significant difference. The only prognostic factor to improve the complete response rate was the hemoglobin level. The patients in Group A, who had Hb <10 gm/dL had the relatively better change to complete response of 1.48 compared to that in Group B (P 0.025, 95% CI 1.07, 2.04). No severe toxicity or adverse event had been reported. The median follow-up time for Group A and Group B was 12.6 and 11.8 months, respectively. There was no statistical difference in PFS and OS. CONCLUSION: Concurrent chemoradiation by Tegafur-Uracil and carboplatin showed no difference in tumor response rate or treatment toxicity compared to carboplatin alone. The combination drugs might have benefit in poor prognostic patients such as the baseline Hb <10 gm/dL.     

Neoadjuvant intra-arterial infusion chemotherapy induces apoptotic cell death in locally advanced uterine cervical carcinomas. A preliminary report

Ueda M, Ueki K, Kumagai K, Terai Y, Kanemura M, Ueki M. Neoadjuvant intra-arterial infusion chemotherapy induces apoptotic cell death in locally advanced uterine cervical carcinomas. A preliminary report. Int J Gynecol Cancer 1998; 8 :144–149.
The purpose of this study was to evaluate the mechanism which leads to cell death in locally advanced uterine cervical carcinoma treated by neoadjuvant intra-arterial infusion chemotherapy (IAC). Cancer tissues surgically obtained from 11 patients (stages Ib-IIIb) receiving preoperative IAC of two courses of mitomycin-C (10 mg/m²), therarubicin (10 mg/m²) and cisplatin (100 mg/body), were examined. Biopsy specimens from the 11 patients before IAC were also used. Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end-labeling (TUNEL) and immunohistochemical staining with anti-P53 and bcl-2 antibodies were performed for cancer tissues from these 11 patients before and after IAC. The evaluation of the clinical response to IAC revealed complete response (CR) in two patients, partial response (PR) in five, and stable disease (SD) in four. Careful observation of routine H. & E. sections showed some tumor cells with apoptosis, especially in patients with CR and PR. Intense TUNEL signals were observed both in ordinary, nonpyknotic nuclei of tumor cells and in nuclear fragments corresponding to apoptotic bodies. Apoptotic indices (AI) of the seven patients with CR or PR after IAC were significantly higher than those before IAC. There was no obvious correlation between apoptosis and P53 expression, but bcl-2 immunoreactivity was markedly decreased after IAC. These results suggest that the antitumor effects of neoadjuvant IAC are closely associated with apoptotic cell death in locally advanced cervical carcinomas.     

Locally advanced adenocarcinoma and adenosquamous carcinomas of the cervix compared to squamous cell carcinomas of the cervix in Gynecologic Oncology Group trials of cisplatin-based chemoradiation

Objective

Conflicting results have been reported for adeno- and adenosquamous carcinomas of the cervix with respect to their response to therapy and prognosis. The current study sought to evaluate impact of adeno- and adenosquamous histology in the randomized trials of primary cisplatin-based chemoradiation for locally advanced cervical cancer.

Methods

Patients with adeno- and adenosquamous cervical carcinomas were retrospectively studied and compared to squamous cell carcinomas in GOG trials of chemoradiation.

Results

Among 1671 enrolled in clinical trials of chemoradiation, 182 adeno- and adenosquamous carcinomas were identified (10.9%). A higher percentage of adeno- and adenosquamous carcinomas were stage IB₂ (27.5% versus 20.0%) and fewer had stage IIIB (21.4% versus 28.6%). The mean tumor size was larger for squamous than adeno- and adenosquamous. Adeno- and adenosquamous carcinomas were more often poorly differentiated (46.2% versus 26.8%). When treated with radiation therapy alone, the 70 patients with adeno- and adenosquamous carcinoma of the cervix showed a statistically poorer overall survival (p = 0.0499) compared to the 647 patients with squamous cell carcinoma of the cervix. However, when treated with radiation therapy with concurrent cisplatin-based chemotherapy, the 112 patients with adeno- and adenosquamous carcinomas had a similar overall survival (p = 0.459) compared the 842 patients with squamous cell carcinoma. Adverse effects to treatment were similar across histologies.

Conclusion

Adeno- and adenosquamous carcinomas of the cervix are associated with worse overall survival when treated with radiation alone but with similar progression-free and overall survival compared to squamous cell carcinomas of the cervix when treated with cisplatin based chemoradiation.     

Neoadjuvant chemotherapy in cervical cancer: a 67 patients experience

The purpose of this study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy in patients with locally advanced cervical cancer. Between 1992 and 2003, all consecutive women with locally advanced cervical cancer receiving neoadjuvant chemotherapy were identified. Sixty-seven patients received neoadjuvant chemotherapy: 34 had stage I disease, 28 had stage II disease, and 5 had stage III disease. Clinical response to neoadjuvant chemotherapy occurred in 61 patients, including six with complete and 55 with partial response; five women showed stable disease and one progressed. After neoadjuvant chemotherapy, 58 women underwent surgery, whereas the remaining nine received radiation. Hematologic toxicity was seen in 14 patients, with most of them consisting in severe anemia. The 5-year survival rate and median survival were 63% and 93 months. In univariate analysis, response to neoadjuvant chemotherapy, treatment after neoadjuvant chemotherapy, cervical stromal invasion >50%, and lymph node involvement were important prognostic factor responsible for survival. Neoadjuvant chemotherapy followed by surgery seems to be tolerated and active in the treatment of locally advanced cervical cancer and might be an alternative choice of therapy to chemoradiation. A prospective randomized trial with a larger number of cases is needed.     

Neoadjuvant intraarterial infusion chemotherapy with a combination of mitomycin-C, vincristine, and cisplatin for locally advanced cervical cancer: a preliminary report.

Combination chemotherapy including cisplatin was administered intraarterially from the internal iliac artery as neoadjuvant chemotherapy to six patients with locally advanced uterine cervical cancer (stage higher than IIIB of FIGO). The drugs and doses were mitomycin-C 10 mg/m2, vincristine 1 mg/m2, and cisplatin 50 mg/m2. Two or three courses were repeated at intervals of 3 weeks. In three patients, dose reductions were undertaken for decreased renal function and thrombocytopenia. Partial response was, however, observed in all patients (response rate 100%), and five of six patients were able to undergo a radical hysterectomy. The major toxic effects were leukocytopenia, nausea, and vomiting. Our preliminary experience suggests that pelvic intraarterial infusion of combination chemotherapy is effective against primary and advanced uterine cervical cancer, and this preoperative treatment can lead to easier radical hysterectomy. However, further studies are warranted.     

Pilot study of concurrent cisplatin, 5-fluorouracil, and external beam radiotherapy prior to radical surgery +/- intraoperative electron beam radiotherapy in locally advanced cervical cancer.

PURPOSE: The purpose of this study was to describe the feasibility of a combined preoperative chemoradiation program followed by radical surgery in advanced cervical cancer. MATERIALS AND METHODS: From February 1988 to April 1997, 40 patients with carcinoma of the cervix were treated with preoperative external beam radiotherapy to 45 Gy in 5 weeks. Patients received concurrent continuous infusion cisplatin (20 mg/m2) and 5-fluorouracil (1500 mg) chemotherapy during the first (days 1-4) and fifth (days 22-25) weeks of the radiation course. Radical surgery was performed 4-6 weeks after the completion of the preoperative treatment. Intraoperative radiotherapy was given to 20 patients, based on intraoperative assessment. RESULTS: Toxicity associated with chemoradiation was usually mild except in two patients who presented WHO grade 4 bone marrow aplasia. Three patients developed postoperative ureterovaginal fistula, and five patients developed long-term hydronephrosis that needed ureteral stenting. Clinical response was observed in 95% of the patients (55% complete response). The analysis of the surgical specimens revealed complete pathological response in 67.5% of the cases and partial pathological response in 32.5%. As expected, the degree of pathological response was predicted by the degree of clinical response (P = 0.001). Nine-year local control, distant metastases-free survival, disease-free survival, and overall survival were 86, 84, 81, and 85%, respectively. Patients displaying a complete pathological response had statistically significant improved local control (P = 0.004), distant metastases-free survival (P = 0.009), disease-free survival (P = 0.002), and overall survival (P = 0.038). CONCLUSIONS: Cisplatin plus 5-fluorouracil preoperative chemoradiation is active and usually well tolerated in locally advanced carcinoma of cervix, inducing a high rate of clinical and pathological complete responses. When this therapy is followed by radical surgery, the local control rates are excellent, even in patients with advanced stages or poor response. These improved local control rates may be achievable only through extensive surgical resection, with a parallel increase in the complication rates.     

局部晚期宫颈癌新辅助化疗和放疗联合治疗

铂类为基础的同步放化疗在美国国立综合癌症网络（NCCN）指南中被认为是局部晚期宫颈癌的标准治疗方案,而在欧洲、日本、韩国以及拉丁美洲,局部晚期宫颈癌的其他治疗方式被认为具有同样的治疗效果。目前我国医疗机构水平参差不齐,放疗设备不一,新辅助化疗（NACT）联合放疗或同步放化疗不失为一种可选择的方法。不可忽视手术在局部晚期宫颈癌中的作用,新辅助化疗仅是局部晚期宫颈癌综合治疗措施中的一部分,临床应用需谨慎,不可滥用,不能将NACT作为单一的、主要的治疗手段。     

Radiochemotherapy for patients with locally advanced cervical cancer: early results

PURPOSE: Radiotherapy is the standard treatment for locally advanced cervical cancer. Recent results of the prospective randomized trials have shown an overall survival and local control advantage for cisplatin-based therapy given concurrently with radiation therapy. Thirty-nine patients who received concurrent chemoradiation between October 1999 and December 2000 were evaluated for treatment response, local control and toxicity. MATERIALS AND METHODS: Thirty-nine patients with Stage IB through IVA cervical carcinoma received weekly cisplatin (40 mg/m2) concurrent with radiotherapy. Thirty-two patients received both external and intracavitary radiotherapy and seven patients received only external radiotherapy because of insufficient tumor response for intracavitary application. Total external radiotherapy dose was 64.8 Gy with 1.8 Gy daily fractions in patients who received only external radiotherapy. Midline shielding was performed at 50.4 Gy in patients who were going to receive brachytherapy and the total external radiotherapy dose was 54-59.4 Gy. Brachytherapy was performed with a Rotterdam applicator via the microSelectron HDR machine. A total dose of 8.5-18 Gy was applied to point A. RESULTS: Median age was 55. Distribution by stages were as follows: Stage IB 5.1%, IIA 28.2%, IIB 43.6%, IIIA 7.7%, IIIB 12.8% and IVA 2.6%. Histologically 33 (84.6%) were epidermoid carcinoma, one was adenocarcinoma, two were undifferentiated carcinoma, one was malignant epithelial tumor. In two patients histological type could not be specified. The median duration of follow-up was 20 months. Four patients had local recurrence and three developed distant metastases. Thirty patients (76.9%) had complete response, eight had (20.5%) partial response and one had (2.6%) stable disease. During or after radiochemotherapy 46.2% of the patients developed toxicity due to chemotherapy. Early and late radiation morbidity rates were 66.7% and 71.8%, respectively. No grade III-IV toxicity was observed. CONCLUSION: Concurrent chemoradiation for locally advanced cervical cancer is the treatment of choice in suitable patients providing high response rates with acceptable toxicity.     

Residual pelvic lymph node involvement after concomitant chemoradiation for locally advanced cervical cancer

OBJECTIVE: Concomitant chemoradiation (and brachytherapy) has become the standard treatment for locally advanced cervical cancers (FIGO stage IB2 to IVA). Adjuvant surgery is optional. The aim of this study was to evaluate the rate of residual positive pelvic lymph nodes after chemoradiation. METHODS: From February 1988 to August 2004, 113 patients with locally advanced cervical cancer have been treated by chemoradiation followed by an adjuvant surgery with a pelvic lymphadenectomy performed (study group). A para-aortic lymphadenectomy had also been performed in 85 of them. RESULTS: The mean age of the patients was 48.4 years (27-74). FIGO stage was: IB2 in 17.7% (20/113), II in 44.2% (50/113), III in 21.2% (24/113) and IVA in 16.8% of the patients (19/113). The mean number of removed nodes was 11.5 (median 11) in pelvic, and 7.5 (median 7) in para-aortic basins. A pelvic lymph node involvement was present in 15.9% (18/113) of the patients after chemoradiation. In 11 patients, only one node was positive. 11.7% (10/85) of the patients had a para-aortic lymph node involvement. A residual pelvic lymph node disease has been observed in 6.3% (4/63) of the cases with no residual cervical disease (or microscopic) versus 26.5% (13/49) of the cases with macroscopic residual cervical tumor (P = 0.003). CONCLUSIONS: Our experience shows that a pelvic lymph node involvement persists in about 16% of the patients after chemoradiation. We can make the assumption that performing a pelvic lymphadenectomy along with the removal of the primary tumor after chemoradiation could reduce the rate of latero-pelvic recurrences, whatever the para-aortic lymph node status.     

Neoadjuvant chemotherapy using low-dose consecutive intraarterial infusions of cisplatin combined with 5-fluorouracil for locally advanced cervical adenocarcinoma

OBJECTIVE: The goal of this work was to evaluate response rate, toxicity, and survival in treatment with intraarterial 5-fluorouracil (5-FU) and cisplatin in a neoadjuvant setting; this combination was administered to patients with locally advanced cervical adenocarcinoma. METHODS: Eleven patients were treated with preoperative neoadjuvant chemotherapy. Those eligible included patients with previously untreated stage IB, II, or III adenocarcinoma with good performance status. Treatment consisted of bilateral internal iliac artery infusion of cisplatin (a total of 10 mg/day) for 30 min, followed by 5-FU (a total of 250 mg/day) given by 24-hour continuous infusion for 10 days. Treatment was repeated every 3 weeks for a total of two or three cycles. All except one patient with progressive disease underwent radical hysterectomy following neoadjuvant chemotherapy. Postoperative radiotherapy was given to the whole pelvis to 6 patients; 3 of the 6 patients with involved common iliac nodes received radiotherapy to a paraaortic field in addition to the whole pelvis. RESULTS: Among 11 eligible patients, 7 had a partial response (64%). Stable disease was observed in 3 cases (27%) and progressive disease in 1 (9%). Histopathological changes related to chemotherapy, however, revealed only mild effects. Of the 24 treatment cycles administered, no Grade 3 or 4 toxicity was observed and there were no therapy-related deaths. The median follow-up period was 30 months (range, 1-65 months). The mean survival period was 34.7 months and the 5-year survival rate was 21.2%. CONCLUSIONS: Intraarterial neoadjuvant chemotherapy effectively reduced tumor size in patients with locally advanced cervical adenocarcinoma; however, a survival advantage was not clear.     

External beam radiotherapy and high-dose brachytherapy combined with cisplatin and paclitaxel in patients with advanced cervical carcinoma

OBJECTIVE: The aim of the present study was to evaluate toxicity and efficacy of concurrent chemoradiation with cisplatin and paclitaxel and high-dose rate (HDR) brachytherapy in patients with locally advanced cervical cancer. PATIENTS AND METHODS: 19 patients with locally advanced cervical carcinoma were treated with external beam radiotherapy (EBRT) to the pelvis +/- paraaortic nodes, HDR brachytherapy, cisplatin at doses of 50 mg/m2 in weeks 1 and 4, and weekly paclitaxel at 50 mg/m2 in weeks 1-5 during years 2000-2002. Chemotherapy was administered until leukopenia < or = 2500/mm3, thrombocytopenia <100,000/mm3, and/or hemoglobin level <100 g/l occurred. The median follow up was 36 months (range 25-47). RESULTS: Only four patients were able to tolerate the complete intended course of radiochemotherapy. Chemotherapy was stopped in two patients because of allergic reaction and in one patient because of deep thrombosis. In 12 other cases, chemotherapy was discontinued for hematological toxicity. The 3-year disease free survival was 66%, the 3-year overall survival was 74%. CONCLUSION: The hematological toxicity was the main factor limiting administration of cisplatin at 50 mg/m2 in weeks 1 and 4 and weekly paclitaxel at 50 mg/m2 in weeks 1-5 concomitantly with extended field radiotherapy of locally advanced cervical carcinoma.     

Neuroendrocrine tumors of the uterine cervix: A therapeutic challenge for gynecologic oncologists

Neuroendocrine tumors (NETs) are aggressive diseases developing from neuroendocrine cells that most frequently involve the gastro-entero-pancreatic tract and the lung, but more rarely are found in almost all body tissues. Limited biological and clinical data are currently available for NETs in uncommon sites, such as female genital tract. NETs represent 0.9% to 1.5% of the tumors of the uterine cervix. They are more likely to have lymph-vascular space invasion and lymph node involvement, and to develop local and distant relapses when compared with the mostly common cervical squamous cell carcinomas or adenocarcinomas. Positive immunostaining for synaptophysin, chromogranin, CD56, and neuron-specific enolase is often detected in cervical NETs .The most recent editions of the World Health Organization Classification of Gynecologic Tract tumors grouped cervical carcinoid tumor and atypical carcinoid tumor into low-grade NETs and cervical small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma into high-grade NETs. High-risk HPV DNA is detected in almost all cervical high-grade NETs. No treatment guidelines, based on prospective, well-designed clinical trials, are currently available due to the rarity of these tumors. Many authors have reported different multimodality approaches, mainly derived from NETs of the lung. These usually consist in radical hysterectomy followed by adjuvant chemotherapy or concurrent chemoradiation for early stage disease, definitive concurrent chemoradiation sometimes preceded by neoadjuvant chemotherapy and followed by adjuvant chemotherapy for locally advanced disease, and palliative chemotherapy for metastatic disease. In this systematic review, we address the histologic classification of cervical NETs, analyze their pathogenesis and overall prognosis, and evaluate the different treatment modalities described in the literature, in order to offer a possible algorithm that may help the clinicians in diagnosing and treating patients with these uncommon and aggressive malignancies.     

Tumor Response to Neoadjuvant Chemotherapy Correlates with the Expression of P-Glycoprotein and PCNA but Not GST-π in the Tumor Cells of Cervical Carcinoma

Objective.To identify the clinicopathological and chemoresistant factors predicting the response to neoadjuvant chemotherapy and the patient prognosis in high-risk cervical carcinomas.Methods.We retrospectively reviewed 47 patients with locally advanced or bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil (5-FU), followed by radical hysterectomy at our hospital between 1988 and 1995. Expressions of the chemoresistance-related proteins, such as P-glycoprotein, glutathioneS-transferase π (GST-π), and proliferating cell nuclear antigen (PCNA) in the tumor cells, were examined by immunohistochemistry using pretreatment biopsy specimens. These results were compared with the chemotherapeutic response, which was evaluated by magnetic resonance imaging (MRI) and histopathology. Outcome of the patients was also studied.Results.Chemotherapeutic effect of either complete (CR) or partial (PR) response on MRI was obtained in 36 of the 47 (86%) patients. Poor response to chemotherapy was significantly correlated with P-glycoprotein expression (P< 0.005) and low PCNA labeling (P< 0.05), but not GST-π expression in the tumor cells. Independent prognostic factors for patient survival were parametrial involvement and lymph node metastasis. Neither the expression of GST-π nor PCNA was correlated with the patient survival.Conclusion.Assessment of the expression of P-glycoprotein and PCNA is potentially useful for the prediction of tumor response to neoadjuvant chemotherapy for cervical carcinomas.     

根治性同步放化疗前淋巴结清扫在局部晚期宫颈癌诊疗中的意义

宫颈癌是威胁女性健康的第四大肿瘤,分期主要基于临床检查。2018年10月国际妇产科联盟(FIGO对宫颈癌分期进行了修改,强调了盆腔及腹主动脉旁淋巴结的转移情况。对于根治性同步放化疗的患者,淋巴结转移与放疗肿瘤控制率密切相关。由于腹主动脉旁淋巴结转移的情况决定了是否扩大放疗照射野,放疗对于较大的淋巴结控制效果不理想,因此在根治性放化疗前手术评估淋巴结情况、切除增大的淋巴结,有助于分期及减瘤,进行个体化的治疗。但手术分期为有创操作,存在相关风险,可能推迟放疗起始时间,缺乏前瞻性的随机对照研究,此治疗方式并未被广泛认可。综述根治性放化疗前手术清扫淋巴结分期的相关文献。     

Pretreatment laparoscopic surgical staging in locally advanced cervical cancer: preliminary results in Korea

OBJECTIVES: The purpose of this study was to evaluate the feasibility and efficacy of pretreatment laparoscopic surgical staging in the treatment of locally advanced cervical cancer. METHODS: Forty-four patients with locally advanced cervical cancer who underwent pretreatment laparoscopic surgical staging between October 2001 and April 2004 were reviewed. The pathological diagnosis after laparoscopic surgical staging was compared with results from preoperative magnetic resonance imaging (MRI), and surgical results with follow-up data were evaluated. RESULTS: The mean duration of surgery was 202.0 (range: 120-300) min and the mean number of harvested lymph nodes (LNs) was 38.7 (range: 20-75). Twenty (45.5%) patients had pelvic LN metastasis and 5 (11.4%) patients had pelvic and para-aortic LN metastasis. Region-specific findings of MRI resulted in sensitivity and positive predictive values of 55.9% and 48.7%, respectively, on a three-region analysis. When compared with MRI, laparoscopic surgical staging was superior in detecting microscopic LN metastasis. The time to commencing concurrent chemoradiotherapy after laparoscopic surgical staging was 8.6 +/- 3.3 (mean +/- SD) days. All the patients received concurrent chemoradiotherapy as scheduled. There were three (6.8%) cases of minor postoperative complications, and no mortality occurred during the follow-up period. The 2-year disease-free survival rate of the current study was 89.7%, and three (6.8%) patients experienced recurrence after treatment. CONCLUSIONS: Laparoscopic surgical staging in locally advanced cervical cancer is a feasible and safe pretreatment method, and can be used as a best guideline for individualized concurrent chemoradiotherapy.     

局部晚期宫颈癌100例淋巴结转移特点及临床分析

目的：探索局部晚期（ⅠB2/ⅡA2期）宫颈癌的淋巴结转移特点及新辅助化疗对预后及并发症发生率的影响。方法：回顾性分析2008年1月-2016年12月南京医科大学第一附属医院收治的424例ⅠA2～ⅡA2期宫颈鳞癌或腺癌患者的临床资料,随访每位患者的生存情况,比较局部晚期宫颈癌患者淋巴结转移情况及新辅助化疗和直接手术患者在手术并发症及预后方面的差异。结果：共424例宫颈癌患者纳入研究,100例局部晚期宫颈癌患者中有68例直接行根治性手术治疗,32例先行1～2次介入或静脉新辅助化疗后行宫颈癌根治术,术后病理提示盆腔淋巴结转移者20例,没有发现腹主动脉旁淋巴结转移。单因素分析提示深肌层浸润、淋巴脉管间隙浸润（lymph vascular space invasion,LVSI）与淋巴结转移相关（P＜0.05）;组织学类型、分化程度、是否行新辅助化疗与淋巴结转移无关（P＞0.05）。将有统计学意义的单因素进行Logistic回归分析显示,LVSI为淋巴结转移的独立危险因素（P＜0.05）。新辅助化疗组淋巴结转移率为22.2％,手术组则为17.2％,2组比较差异无统计学意义（P＞0.05）。总生存期及无瘤生存期方面,局部晚期宫颈癌明显低于早期者。新辅助化疗组的术后感染发生率较低,手术时间和腹腔引流管留置时间较短,但2组差异无统计学意义（P＞0.05）,而术中输尿管支架置入率、输血率、其他相邻脏器损伤的发生率2组相似。结论：局部晚期宫颈癌预后较早期差,淋巴结转移率明显高于早期,盆腔淋巴结转移主要与LVSI及深肌层浸润有关。新辅助化疗对局部晚期宫颈癌的影响尚不明确,也没有证据证明新辅助化疗影响盆腔淋巴结转移的检出率,在手术相关并发症的发生率方面还需更大样本或多中心的研究。     

Feasibility and safety of type C2 total extraperitoneal abdominal radical hysterectomy (TEARH) for locally advanced cervical cancer

Introduction

Radical hysterectomy represents the gold standard treatment in patients with early-stage cervical cancer and a valid choice of treatment, after neoadjuvant chemotherapy (NACT), in locally advanced tumors. Laparotomy is still considered the standard approach for radical hysterectomy; however, the extraperitoneal route has been described as a valid alternative for pelvic lymphadenectomy, with shorter operative time, shorter ileus and reduced postoperative pain and hospitalization. We designed the first prospective study to evaluate the technique of total extraperitoneal radical hysterectomy for surgical treatment of locally advanced cervical cancer after platinum-based NACT, in terms of feasibility and safety.

Methods

Consecutive patients affected by locally advanced cervical carcinoma were considered for eligibility in this observational study. After a primary complete evaluation, all patients were submitted to platinum-based NACT. Inclusion criteria were: stage IB2-IIIB cervical carcinoma already submitted to neoadjuvant chemotherapy with a complete or partial response after three cycles of chemotherapy, WHO performance status ≤ 1, adequate renal, hepatic and cardiac function, BMI < 40, age ≤ 75 years, no concurrent or previous malignant disease, no previous radiation therapy, and signed informed consent. Patients included in the study were submitted to type C2 extraperitoneal radical hysterectomy.

Results

From January 2006 to October 2008, 46 patients were enrolled and compared with a control group selected from the historical database. The mean operative time in the extraperitoneal radical hysterectomy group was 195 min (range: 120-240) versus 235 min (range: 215-310) in the intraperitoneal radical hysterectomy group (P < 0.05). Median postoperative ileus was 32 h (range: 24-36) versus 67 h (range: 42-78) (P < 0.05). VAS (Visual Analogue Scale) score at 24 and 48 h was 8 (range: 6-8) versus 8 (range: 6-9) (P = NS) and 3.5 (range: 2-7) versus six (range: 5-9) (P < 0.05) respectively. No differences in terms of intraoperative and postoperative complications were recorded.

Conclusions

Total extraperitoneal radical hysterectomy in locally advanced cervical cancer is feasible and safe. If compared with intraperitoneal abdominal radical hysterectomy, no significant differences in terms of surgical data or complications were found. Extraperitoneal radical hysterectomy seems to compare favorably to the intraperitoneal approach in terms of operative time, postoperative ileus, and VAS score at 48 h.     

Ten-year survival of patients with locally advanced, stage ib-iib cervical cancer after neoadjuvant chemotherapy and radical hysterectomy.

OBJECTIVE(S). The aim of this study was to evaluate the effects of neoadjuvant chemotherapy and radical hysterectomy on long-term survival in stage IB-IIB locally advanced cervical cancer by conducting a 10-year follow-up. METHODS: Between August 1983 and May 1990, 80 locally advanced, stage IB-IIB cervical cancer patients with tumor diameter greater than or equal to 4 cm were treated with neoadjuvant VBP chemotherapy (cisplatin, vinblastine, and bleomycin) followed by radical hysterectomy with pelvic lymphadenectomy. After this therapeutic modality, patients were followed for more than 10 years. Ten-year survival rates and factors affecting recurrence after this therapy were evaluated. RESULTS: Of 80 patients, 75 (93.7%) showed a reduction in tumor size after neoadjuvant chemotherapy. At pathologic examination, stage reduction was noted in 53 (66.2%) patients and 20 patients (25%) showed no residual or microinvasive cervical tumor. Pelvic lymph node metastases were found in 17 patients (21.3%). During the 10-year follow up, 2 patients were lost and 16 patients recurred. Overall 5-year and 10-year disease-free actual survival rates were 82.0 (64/78) and 79.4% (62/78), respectively. Clinical stage, initial tumor size, clinical response, and residual tumor size were not risk factors for recurrence after this therapy. However, pelvic lymph node metastasis was a significant risk factor for recurrence. CONCLUSION(S). Neoadjuvant VBP chemotherapy followed by radical hysterectomy in locally advanced, stage IB-IIB cervical cancer patients seemed to improve the long-term survival rate for these patients compared to that of conventional therapy. However, randomized controlled trials are needed to confirm this result.     

子宫颈癌术前辅助治疗的规范化

新辅助化疗(neoadjuvant chemotherapy,NACT)是子宫颈.癌术前或放疗前辅助治疗的主要方式,原则上适用于局部晚期(Ⅰ B3～ⅣA期)和部分特殊类型的子宫颈癌患者.顺铂为首选药物,推荐化疗2～3个疗程.肿瘤直径大于4cm的Ⅰ B3～ⅡA2期的子宫颈鳞癌和腺癌的部分患者可以采用新辅助化疗+根治性手术...     

Concurrent chemoradiation in advanced cervical cancer

The pelvis is the predominant site of failure following radical radiotherapy (RT) for locally advanced cervical cancer. We report the results of phase I-II studies on 200 patients with bulky (greater than or equal to 5 cm) carcinoma of the cervix. Patients were treated between 1981 and 1988 on sequential protocols of concurrent chemoradiation to establish an acceptable treatment regimen. RT with daily or partially hyperfractionated pelvic (n = 154) or pelvic plus paraaortic (n = 46) fields was given by continuous (n = 154) or split course (n = 46) regimens. Infusional fluorouracil (5-FU) in a dose of 1 g/m2/day was given on the first and last 4 days of a 5-week course of continuous RT, or with both halves of split course RT. Seventy-eight patients received bolus mitomycin C (Mit-C), 6 mg/m2, once or twice with the start of the 5-FU infusion. The median external RT dose was 46 Gy (range 40 to 65 Gy) followed in 90% (n = 181) by a single intracavitary application of 40 Gy using a linear source of cesium-137. Median follow up is 2.5 years (range 0.6 to 6.9 years) and is sufficient to reliably estimate late toxicities. Acute toxicities were transient oral mucositis (13), RT interruption for enteritis (7), febrile neutropenia (3), and thrombocytopenic tumor bleed (1). Serious late toxicities resulted in death in 3 patients and occurred in bladder in 6 and in bowel in 25, including 8 patients with tumor recurrence. The incidence of late bowel toxicity correlated with the specific therapy given and decreased with each successive protocol. On logistic regression the only treatment variable showing a statistically significant effect on complications was the use of Mit-C (P = 0.0053). Pelvic RT and 5-FU alone produced fewer complications, only 4/105, than historically seen with standard pelvic RT alone. Three-year pelvic control and survival rates were 85 and 71% respectively in stage Ib/II (n = 100) and 50 and 42% in stage III/IV (n = 100). Encouraged by these results and decreased toxicity, we have begun a phase III study to determine whether the addition of concurrent 5-FU to continuous partially hyperfractionated pelvic RT improves local control and survival.