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

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

Ⅱb~Ⅲ期宫颈癌264例疗效及预后因素分析

目的探讨Ⅱb~Ⅲ期宫颈癌患者的疗效及预后相关因素。方法分析2007年3月至2008年10月辽宁省肿瘤医院收治的264例宫颈癌患者的临床资料。结果 264例患者的中位随访时间75个月,2、5年总生存率(overall survival,OS)分别为77.7%、65.5%。2、5年肿瘤特异性生存率(disease-specific survival,DSS)分别为78.1%、66.5%。2、5年无病生存率(disease-free survival,DFS)分别为72.7%、64.2%。单因素分析显示,影响OS、DSS、DFS的因素有临床分期(Ⅱb期与Ⅲ期,P0.01),肿瘤大小(4 cm、4~6 cm、6 cm,P0.01)、病理类型(鳞癌与腺癌,P0.01)、阴道受侵范围(无、上1/3、中1/3、下1/3,P0.01)、淋巴结情况(盆腔腹主阴性、仅盆腔阳性、盆腔腹主阳性、未做CT,P0.01)、最低血红蛋白(110 g/L、95~110 g/L、75~95 g/L、52~75 g/L,P0.01)。入院血红蛋白是DFS的影响因素。多因素分析显示,临床分期、病理类型、淋巴结情况、治疗方式、最低血红蛋白为宫颈癌OS、DSS和DFS的独立预后因素。结论Ⅲ期、腺癌、淋巴结阳性、单纯放疗以及最低血红蛋白75 g/L的宫颈癌患者预后不良。     

Uterine papillary serous carcinoma: Patterns of failure and survival

Objective: To evaluate the outcome in patients with uterine papillary serous carcinoma (UPSC).
Methods: A retrospective review of women treated for UPSC between 1995 and 2006 in Westmead Hospital, Sydney. The patients were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy and surgical staging. The majority of the patients had platinum-based adjuvant chemotherapy and radiotherapy. Sites of initial recurrence were documented. Overall survival (OS) and progression free survival (PFS) were estimated using Kaplan–Meier method. Univariate and multivariate analysis was performed using Cox regression analysis to test the effects of multiple prognostic factors on survival.
Results: Two-year and five-year OS was 65% and 43%. The median OS was 39 months. Two-year and five-year PFS was 60% and 35%. Macroscopic residual disease at the completion of surgery was the only significant prognostic factor associated with worse OS on both univariate and multivariate analysis ( P  < 0.001). The median OS was only 11 months if patients had macroscopic residual disease, and all patients died within 18 months despite adjuvant therapies. Twenty-one patients relapsed. The site(s) of initial recurrence were: vagina (five patients), pelvic lymph nodes (four patients), abdomen (11 patients), para-aortic lymph nodes (six patients), inguinal lymph nodes (two patients) and distant metastases in seven patients. Only one of 16 patients who received vaginal brachytherapy failed in the vagina, but three of seven patients who received external beam pelvic radiotherapy failed in the vagina.
Conclusion: We recommend optimal cytoreduction surgery with the aim of leaving no macroscopic disease at the end of the operation. Vaginal brachytherapy should be considered as a component of adjuvant radiotherapy. Abdominal failure was the commonest mode of failure in our cohort of patients.     

Radical hysterectomy alone or combined with neoadjuvant chemotherapy in the treatment of early stage bulky cervical carcinoma.

BACKGROUND AND PURPOSE: Early-stage bulky cervical carcinoma treated with conventional surgery or radiotherapy has a higher rate of recurrence compared to smaller tumors at the same stage. Whether neoadjuvant chemotherapy prior to radical hysterectomy can improve survival in early-stage bulky cervical carcinoma remains unclear. This study was designed to answer this question. METHODS: Fifty-eight women with early-stage bulky cervical cancer were included in this retrospective study. Thirty-one had received neoadjuvant chemotherapy before radical hysterectomy, and the other 27 patients underwent surgery alone. The chemotherapeutic regimen was a combination of cisplatin, vincristine, and bleomycin with a 10-day interval for two to three courses. RESULTS: The age, parity, and tumor diameter before treatment in the two groups were similar. The mean tumor diameter was significantly decreased after neoadjuvant chemotherapy (4.6 +/- 0.8 vs 3.4 +/- 1.5 cm, P = 0.003). Patients without neoadjuvant chemotherapy had a significantly higher incidence of parametrial invasion (14/27 vs 7/31, P = 0.022). More involved lymph nodes were found during surgery in patients without neoadjuvant chemotherapy (23.1 +/- 10.5 vs 17.4 +/- 7.1, P = 0.024), but the incidence of lymph node metastasis was not different between the two groups (18/31 vs 17/27, P = 0.71). The response rate of primary tumor to chemotherapy was 48.4% (15/31). No significant differences in clinical and pathologic parameters were found between responders and non-responders. Deep stromal invasion (> or = 3/4 thickness of cervical stroma) was the only independent prognostic factor for disease-free survival (DFS) and overall survival (OS) in the 58 patients and in the 31 patients who received neoadjuvant chemotherapy. Neither neoadjuvant chemotherapy nor the response to it was an independent prognostic factor for DFS or OS. CONCLUSIONS: Neoadjuvant chemotherapy could reduce the incidence of local invasion for bulky early-stage cervical carcinoma but did not improve the DFS or OS in our patients. Without further randomized study of the effects of neoadjuvant chemotherapy, this treatment should be chosen carefully.     

Long-term outcome and prognostic factors in patients with cervical carcinoma: a retrospective study

This study evaluates treatment outcomes and possible prognostic factors of inoperable cervical cancer patients treated with external beam radiotherapy (EBRT) and high-dose rate brachytherapy (HDR BRT). Between 1993 and 2000, 183 patients with cervical cancer were treated at our institute. Radiotherapy was the sole treatment modality until January 1997; after the announcement of National Cancer Institute in 1999, 40 mg/m(2) of cisplatin (49%) was routinely applied every week. Median age was 54 years (32-92 years). Most patients (88%) had advanced-stage disease (IIB-IIIB). With a median follow-up time of 45 months (6-121 months), the 5-year overall survival (OS), local recurrence-free survival, disease-free survival (DFS), and distant metastasis-free survival (DMFS) rates were 55%, 71%, 51%, and 77%, respectively. Univariate analysis revealed that age, tumor size, lymph node status, and concomitant cisplatin were prognostic factors for OS. The DFS rates were lower in young age group. Patients with tumor greater than 4 cm and age greater than 40 were at greater risk for local recurrence. Distant metastases were more frequent in patients with adenocarcinoma. Concurrent cisplatin use increases DMFS rates (91% vs 78%; P= 0.05). In multivariate analysis, extensive stage, parametrial infiltration, young age, adenocarcinoma histopathology, and lymph node metastasis were negative prognostic factors for OS while concomitant cisplatin increases OS. Likewise, patients with extensive stage, adenocarcinoma, and without concurrent cisplatin administration had more risk for distant metastasis. There was no treatment-related mortality. Grade 3-4 morbidity rates were seen only in eight patients (4%). The combination of EBRT and HDR BRT together with concomitant chemotherapy in the treatment of locally advanced carcinoma of cervix is safe and well tolerated with acceptable morbidity.     

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.     

Radiotherapy in the adjuvant setting of cervical carcinoma: treatment, results, and prognostic factors

To evaluate the efficacy of postoperative radiotherapy and to investigate prognostic factors for early-stage cervical cancer patients. From December 1993 to December 2001, 141 patients with stage I-II cervical cancer without para-aortic lymph node (LN) metastases and treated by surgery and postoperative radiotherapy (RT) were included in this study. Indications for postoperative external RT were based on pathologic findings, including LN metastasis, positive surgical margins, parametrial involvement, pT2 tumor, and presence of any two minor risk factors like lymphvascular space involvement, deep stromal invasion, and tumor diameter between 2-4 cm. Sixty-six (47%) patients received RT alone, whereas 59 (42%) were treated with RT and concomitant chemotherapy (CT), and 16 received neoadjuvant CT. Patients with positive vaginal margins also received 27.5 Gy high-dose rate vaginal cuff brachytherapy in five fractions. Median follow-up time was 55 months. The actuarial 5-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRFS), and distant metastases-free (DMFS) survival rates are 70%, 68%, 77%, and 88%, respectively. Univariate and multivariate analyses revealed that level and number of metastatic LNs and concomitant CT were unique significant prognostic factors for OS, DFS, and LRFS. Endometrial involvement, on the other hand, was proven to be significant for DFS and DMFS. Patients with less than three LN metastases or having only obturator LN involvement showed similar prognosis with their counterparts having no LN metastases. On the other hand, patients with either common iliac LN or more than three LN metastases had significantly worse outcome. Our results indicate that level and number of metastatic LNs are the most important prognostic factors determining the survival rates, and patients with upper lymphatic involvement or more than three metastatic LNs seem to need more effective treatment approaches.     

同步放化疗治疗Ib2和IIa2期宫颈癌疗效及预后相关因素分析

目的:探讨同步放化疗治疗Ib2期和IIa2期宫颈癌的疗效和不良反应,并分析预后影响因素。方法:回顾分析2000年1月至2010年12月首都医科大学附属北京妇产医院妇瘤科收治的73例接受同步放化疗的Ib2和IIa2期宫颈癌患者的临床病理资料。统计有效率和疾病控制率评价近期疗效,统计3年、5年无瘤生存率(DFS)及总生存率(OS)评价远期疗效,记录患者的不良反应,并分析可能影响患者预后的相关因素。结果:同步放化疗治疗Ib2期和IIa2期宫颈癌的有效率(CR+PR)为91.78%,疾病控制率(CR+PR+SD)为97.26%;3年DFS为84.93%,0S为86.30%;5年DFS为79.45%,0S为82.19%。所有不良反应患者均可耐受,对症治疗后均可缓解。单因素分析显示,患者的生存率与肿瘤的病理类型、分化程度、大小、有无淋巴结转移以及治疗前后血鳞状细胞癌抗原(SCC-Ag)值有关(P0.05)。多因素分析表明,肿瘤病理类型、大小、有无淋巴结转移及治疗后1个月血SCC-Ag值为远期疗效的独立影响因素。结论:同步放化疗治疗Ib2期和IIa2期宫颈癌的近、远期疗效肯定,不良反应可耐受,是一种可供选择的方法。病理类型为腺癌、肿瘤直径﹥5cm、有淋巴结转移、治疗后1个月血SCC-Ag值≥1.5ng/ml者预后较差,需进一步加强研究。     

Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy

BACKGROUND: The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy. METHODS: A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors. RESULTS: Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined to the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI was the most important prognostic factor, and histologic type, depth of cervical stromal invasion, and tumor size were not related to survival. The survival of patients with a tumor extending to parametrium or pelvic lymph node(s) was adversely affected by histology of pure adenocarcinoma. When the tumor extended to common iliac or paraaortic nodes, patients' survival became quite poor irrespective of LVSI or histologic type of pure adenocarcinoma. Patients' prognosis could be stratified into low risk (patients with a tumor confined to the uterus not associated with LVSI: n = 80), intermediate risk (patients with a tumor confined to the uterus associated with positive LVSI, and patients with squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma associated with pelvic lymph node metastasis or parametrial invasion, and patients with common iliac/paraaortic node metastasis: n = 21) with an estimated 5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/- 9.7%, respectively. CONCLUSIONS: LN status, parametrial invasion, LVSI, and histology of pure adenocarcinoma are important histopathologic prognostic factors of cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma may be stratified by combined analysis of these histopathologic prognostic factors. Postoperative therapy needs to be individualized according to these prognostic factors and validated for its efficacy using randomized clinical trials.     

Prognostic factors in surgically treated stage ib-iib cervical carcinomas with special emphasis on the importance of tumor volume.

OBJECTIVE: The aim of the study was to analyze the importance of tumor volume as a prognostic factor for overall survival (OS) in surgically treated stage Ib-IIb cervical carcinoma. METHODS: One hundred thirteen of one hundred sixty-five patients with histopathological stage Ib-IIb cervical carcinoma (44 Ib1, 24 Ib2, 10 IIa, 35 IIb) treated by radical abdominal hysterectomy between 1989 and 1999, for whom tumor volume could be assessed, were included in this study. Of the 113 patients, 90 (79.6%) received postoperative radiotherapy. Measurement of tumor volume was performed on giant histological sections using a semiautomatic image analyzer. The prognostic significance of tumor volume was analyzed and compared with that of various clinicopathological parameters using uni- and multivariate statistics. RESULTS: The 5-year disease-free survival was 71.4%. Increasing tumor volume was associated with more frequent lymph node metastases and a significant decrease in OS (P = 0.0112). The Median tumor volume was smaller in stage IIa tumors than in stage Ib2 tumors, and histopathological stage did not correlate linearly with lymph node metastases as well as OS. Stage Ib2 tumors were associated with worse overall survival than stage IIa tumors. In univariate analysis, lymph node metastases, histopathological stage, lymph vascular space involvement, tumor volume, parametrial spread, and tumor involvement of resection margins were significant parameters for OS. In multivariate statistical analysis, only lymph node metastases and histopathological staging remained independent prognostic factors for OS. CONCLUSIONS: Tumor volume does not seem to confer additional prognostic information if histopathological stage and lymph node status are known. However, it may provide important prognostic information if lymph node status is not known or histopathological stage cannot be assessed.     

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

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

Prognostic factors affecting disease-free survival in early-stage cervical cancer patients undergoing radical hysterectomy and pelvic-paraaortic lymphadenectomy

OBJECTIVE: This study was performed to identfy surgical and histopathologic prognostic factors that could predict 5-year disease-free survival (DFS) after patients underwent radical hysterectomy and pelvic-paraaortic lymphadenectomy for FIGO Stage I-II cervical carcinoma. METHODS: A retrospective review was performed for all patients undergoing primary radical hysterectomy and pelvic-paraaortic lymphadenectomy for Stage I-II cervical cancer at Ankara Oncology Hospital from 1995 to 2000. Clinical and pathologic variables including age, tumor size (TS), clinical stage, depth of invasion (DI), lymphovascular space involvement (LVSI), cell type, tumor grade, lymph node metastases (LNM), parametrial involvement, surgical margin involvement and pattern of adjuvant therapy were analyzed using univariate analyses. DFS was performed by the Kaplan-Meier method and the log-rank test. Independent prognostic and predictive factors affecting DFS were assessed by the Cox proportional hazard method. RESULTS: Ninety-three patients underwent primary type III radical hysterectomy and pelvic-paraaortic lymphadenectomy. Five-year DFS was 87.1%. LVSI, parametrial involvement and grade were the prognostic factors that independently affected survival. DFS was not significantly different for age, disease status of the surgical margins, tumor size, depth of invasion, cell type, pelvic lymph node metastases and adjuvant radiotherapy. CONCLUSIONS: LVSI, parametrial invasion and histologic grade 2-3 were independent prognostic factors in early-stage cervical cancer patients. Adjuvant radiotherapy in these patients provides no survival advantage.     

淋巴结转移的Ⅰb 1～Ⅱb期子宫颈癌患者手术后的综合治疗及预后分析

目的研究淋巴结转移的Ⅰb1～Ⅱb期宫颈癌患者广泛性子宫切除加盆腔淋巴结切除术后综合治疗的方式和预后。方法选取1990年1月至2003年6月复旦大学附属肿瘤医院接受手术治疗的Ⅰb1～Ⅱb期淋巴结转移的宫颈癌患者215例。所有患者均接受了广泛性子宫切除加盆腔淋巴结切除术。根据术后治疗情况将患者分为4组：放疗加化疗组（107例）、放疗组（45例）、化疗组（22例）和无辅助治疗组（41例）。通过比较4组患者的临床病理资料,对患者预后及可能影响预后的有关因素进行分析。结果放疗加化疗组、化疗组、放疗组和无辅助治疗组患者的3年无瘤生存率分别为60．7％、53．5％、47．4％和36．0％,放疗加化疗组患者的3年无瘤生存率显著高于无辅助治疗组,两组比较,差异有统计学意义（P=0．001）,而化疗组、放疗组的3年无瘤生存率分别与无辅助治疗组比较,差异无统计学意义（P值分别为0．060和0．159）。放疗加化疗组、化疗组、放疗组和无辅助治疗组患者的盆腔复发率分别为7．5％、22．7％、26．7％和34．1％,远处转移率分别为16．8％、18．2％、15．6％和22．0％,复发合并转移率分别为4．7％、0、4．4％和7．3％。放疗加化疗组盆腔复发率显著低于其余3组,与其余3组比较,差异有统计学意义（P〈0．01）,而远处转移率、复发合并转移率与其余3组比较,差异无统计学意义（P〉0．05）。多因素分析显示,肿瘤直径、病理类型、淋巴结转移数目和术后辅助治疗是影响淋巴结转移的宫颈癌患者预后的重要因素（P〈0．05）。结论淋巴结转移的宫颈癌患者根治性手术后辅助放、化疗能提高3年无瘤生存率,降低盆腔复发率。     

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.     

Post-hysterectomy radiotherapy in FIGO stage IB-IIB uterine cervical carcinoma

OBJECTIVE: This study is a retrospective analysis of stage IB-IIB cervical carcinoma patients who had received postoperative radiotherapy (PORT). METHODS: Eight hundred patients with stage IB-IIB cervical carcinomas who received PORT after radical hysterectomy and bilateral pelvic lymph node dissection (PLND) between February 1979 and March 2000 were analyzed. RESULTS: The median follow-up duration was 100 months. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 88% and 81%, respectively. One hundred forty-six patients (18%) failed, and 103 of these had distant metastases. Multivariate analysis revealed that pelvic lymph node (LN) metastasis significantly compromised OS, DFS, pelvic failure-free survival (PFFS), and distant failure-free survival (DFFS) (P < 0.05). Patients with age <50 years, deep stromal invasion (DSI), and lymphovascular space invasion (LVSI) were significantly associated with a higher risk of distant metastasis after PORT. The incidences of late rectal, urinary, and small bowel complications of grade 3 or higher were 1.6%, 1.4%, and 1.0%, respectively. CONCLUSIONS: PORT achieved good OS and DFS in the patients with risk factors after radical hysterectomy for stage IB-IIB cervical carcinomas. Distant metastasis was the major pattern of treatment failure after PORT. Effective systemic chemotherapy might be a breakthrough in improving the outcome of PORT in patients with cervical carcinomas.     

Significance of tumor volume and corpus uteri invasion in cervical cancer patients treated by radiotherapy

The purpose of this study was to show that in advanced cervical cancer patients treated with curative intent, tumor volume and uterine involvement have independent prognostic value. Eligible patients were those seen at the Peter MacCallum Cancer Centre between December 1995 and June 2001, newly diagnosed with a histologic diagnosis of squamous cell carcinoma or adenocarcinoma of the cervix, FIGO-staged IB-IVA, and having undergone magnetic resonance imaging (MRI) and treated with curative intent. Potential prognostic factors considered were FIGO stage, clinical tumor diameter, histology, age, tumor volume, and corpus invasion status. MRI was used to determine the tumor volume and whether there was invasion of tumor into the corpus uteri. One hundred and seventy-nine patients were eligible for this study. The cut-off date for follow-up was October 2003, one patient was lost to follow-up, and the mean potential follow-up time was 4.5 years (range 0.2-7.7 years). There were 60 (34%), 78 (44%), 34 (19%), and 7 (4%) patients in FIGO stages IB, II, III, and IVA, respectively. The tumors of 107 (60%) patients exhibited corpus invasion. The median tumor volume was 33 mL (range 0.1-200 mL). The four factors, FIGO stage, clinical tumor diameter, corpus invasion, and tumor volume, were all strongly positively correlated (P < 0.001 in each case). The 5-year overall survival (OS) rate for all patients was 55% (standard error = 4%). Of the six factors examined, FIGO stage (P= 0.006), clinical tumor diameter (P= 0.013), corpus invasion (P < 0.001), and tumor volume (P < 0.001) were statistically significantly related to OS duration in unifactor analyses. However, only corpus invasion (P= 0.013) and tumor volume (P= 0.004) were significantly and independently associated with OS in multifactor analyses. In particular, after adjusting for corpus involvement and tumor volume, there was no evidence for any relationship between OS and either FIGO stage (P= 0.49) or clinical tumor diameter (P= 0.58). The results from the analysis of failure-free survival were very similar. We conclude that in patients with advanced cervical cancer, tumor volume and corpus invasion provide important prognostic information over and above that provided by FIGO stage, clinical tumor diameter, histology, and age.     

子宫颈鳞癌Ⅰb～Ⅱa期患者预后预测系统的建立及其临床意义

目的分析子宫颈鳞癌Ⅰb~Ⅱa期患者的预后影响因素并建立预后预测系统,以探讨其在指导术后辅助治疗中的作用。方法回顾性分析接受手术治疗的306例Ⅰb~Ⅱa期宫颈鳞癌患者的临床病理资料,对影响其预后的因素进行单因素和多因素分析。结果306例患者的5年生存率为78 1%。单因素分析结果显示,与其预后有关的因素为淋巴结转移、病理分化程度、肿瘤直径、宫旁组织浸润、深肌层浸润和脉管内瘤栓(P<0 05);多因素分析结果显示,淋巴结转移、深肌层浸润、宫旁组织浸润是影响其预后的独立危险因素(P<0 05)。根据危险因素的不同建立预后预测系统,即将患者分为低危组、中危组和高危组3组,其5年生存率分别为90 3%、83 9%和43 1%。低危组(无危险因素或仅宫旁组织浸润)局部复发的发生率仅为2 2%;中危组(深肌层浸润或合并有宫旁组织浸润)局部复发的发生率为13 5%,远处转移的发生率为1 3%, 局部复发合并远处转移的发生率为0 6%;高危组(淋巴结转移或合并其他危险因素)局部复发和远处转移的发生率分别为25 9%和48 3%,局部复发合并远处转移的发生率为10 3%。结论淋巴结转移、深肌层浸润、宫旁组织浸润是影响Ⅰb~Ⅱa期宫颈鳞癌患者预后的独立因素;根据预后影响因素建立的预后预测系统有助于指导术后辅助治疗。     

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.     

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

PURPOSE OF INVESTIGATION: To identify surgical pathologic factors that best correlate with administration of adjuvant radiotherapy and best predict survival in early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection (RHND). METHODS: Data from the files of 126 patients with cervical carcinoma treated by RHND at the Soroka Medical Center from 1962 through 2005 were analyzed. RESULTS: Fifty-four percent of the patients received postoperative adjuvant radiotherapy. In a univariate analysis, each of the following factors: positive pelvic lymph nodes, lower uterine segment involvement, lymph vascular space involvement, penetration > or = 50% of the cervical wall, grade 2+3, parametrial and/or paracervical involvement, vaginal margin involvement, non-squamous histologic type, tumor size > or = 3 cm and Stage IB2 + IIA was significantly associated with administration of radiotherapy. In a multivariate analysis, positiviy of pelvic lymph nodes was persistently the most significant factor associated with administration of radiotherapy. The 5-year survival rate was 82.6% overall. In a univariate analysis, a significant worsening in survival was demonstrated with positivity of pelvic lymph nodes and positivity of lymph vascular space involvement. In a "better fit" model of multivariate analysis, pelvic lymph node status was the strongest and the only significant predictor of survival. CONCLUSIONS: In patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection, pelvic lymph node status is the strongest factor affecting administration of adjuvant radiotherapy and the most significant predictor of survival.     

The significance of thrombocytosis in patients with locally advanced cervical carcinoma: a Gynecologic Oncology Group study

OBJECTIVE: The aim of this study was to determine the incidence of thrombocytosis and its possible impact on survival probability among women with locally advanced cervical carcinoma. METHODS. The database of 294 patients with Stages IIB-IVA cervical carcinoma without periaortic node metastasis who were treated with standardized radiation therapy and concurrent hydroxyurea or misonidazole was analyzed. Pretreatment platelet counts were available for 291 patients who are the subject of this study. RESULTS. Thrombocytosis (platelet count >400 x 10(9)/liter) was present in 86 (29.6%) of the 291 patients. A multivariate Cox proportional hazards model showed that patients without extrapelvic disease and with thrombocytosis had a 55% greater chance of dying than those without thrombocytosis (relative risk = 1.55, 95% confidence interval 1.08-2.21). Patients with thrombocytosis had larger tumors and more frequently had bilateral parametrial involvement, tumor fixation to the sidewall, and positive pelvic lymph nodes than patients without thrombocytosis. Thrombocytosis was not found to be a prognostic factor in patients with positive pelvic nodes. However, in patients with negative pelvic nodes, the presence or absence of thrombocytosis was related to survival. CONCLUSION: Thrombocytosis is a frequent finding among patients with advanced cervical carcinoma and seems to be related to tumor burden. Among patients with locally advanced cervical carcinoma who had negative pelvic nodes, those with thrombocytosis had a poorer survival.