Sentinel lymph Node mapping versus systematic pelvic lymphadenectomy on the prognosis for patients with intermediate-high-risk Endometrial Cancer confined to the uterus before surgery: trial protocol for a non-inferiority randomized controlled trial (SNEC trial).

BACKGROUND: Sentinel lymph node (SLN) mapping has been recommended as an alternative staging approach to lymphadenectomy for apparent uterine-confined endometrial cancer (EC). However, the prognostic value of SLN mapping alone instead of systematic lymphadenectomy on EC patients remains unclear. METHODS: A multi-center, open label, non-inferiority randomized controlled trial has been designed to identify if SLN mapping alone is not inferior to pelvic lymphadenectomy on prognosis of patients with intermediate-high-risk EC clinically confined to uterus. Eligible patients will be 1:1 randomly assigned to accept SLN mapping or pelvic lymphadenectomy. The primary endpoint is the 2-year progression-free survival (PFS). The second points are the 5-year PFS, 5-year overall survival, surgery-related adverse events and life quality. A total of 780 patients will be enrolled from 6 hospitals in China within 3-year period and followed up for 5 years. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04276532.

Surgical and oncological outcomes of an improved nerve-sparing radical hysterectomy technique: 6 years of experience at two centres.

OBJECTIVE: An improved nerve-sparing radical hysterectomy (NSRH), which is based on the paravesico-vaginal space, has been recently introduced in a phase II, prospective clinical trial by our team. This study aims to report the surgical and oncological outcomes of this improved NSRH. METHODS: One hundred seventy-seven consecutive patients were enrolled in our study and underwent the improved NSRH. The proportion of successful catheter removal and postvoid residual urine volume (PVR) of 50 mL or less at postoperative day 7 or day 4 was used to assess surgical outcomes. The local control rate (LCR), disease free survival (DFS), and overall survival (OS) were used to assess oncological outcomes. RESULTS: Postoperative 30-day complications occurred in 27/177 (15.3%) patients. The rate of successful catheter removal and PVR of 50 mL or less were 85.2% (23/27) and 66.7% (18/27) at postoperative day 7, and 73.3% (110/150) and 35.3% (53/150) at postoperative day 4. A total of 13 (7.9%) patients showed recurrence after a median follow-up time of 39.2 months (range 3.2-68.1 months). The estimated 2-year and 5-year DFS rates were 92.2% and 91.1%, respectively. Seven (4.2%) patients presented local recurrence, and five (3.0%) patients were dead at the end of the follow-up period. The estimated 5-year LCR and OS were 95.1% and 96.2%, respectively. In univariate analysis, International Federation of Gynecology and Obstetrics (FIGO) stage, lymphovascular space invasion (LVSI), and lymph node metastasis were found to be the prognostic risk factors of DFS. Patients with LVSI were associated with a worse DFS according to the multivariate analysis. CONCLUSIONS: The improved NSRH in our study may provide better surgical outcomes without compromising the survival in patients with early cervical cancer.

A prospective study of fertility-sparing treatment with megestrol acetate following hysteroscopic curettage for well-differentiated endometrioid carcinoma and atypical hyperplasia in young women.

PURPOSE: To investigate the feasibility and efficacy of curettage with hysteroscopy followed by megestrol acetate (MA) for well-differentiated endometrioid carcinoma (EC) confined to the endometrium and for atypical hyperplasia (AH) in young women. PATIENTS AND METHODS: Fourteen patients with EC and 12 patients with AH were prospectively enrolled in this study. All of the patients received at least 12 weeks of oral MA (160 mg/day) following thorough curettage with hysteroscopy. The response was assessed histologically every 12 weeks. The primary endpoint was the complete response rate. Adverse events, pregnancy rates and recurrence rates were secondary end points. RESULTS: Twenty-one (80.8 %) patients responded to treatment. The median time to response was 12 weeks. After a median follow-up of 32 months, 6 patients had recurrences. Significantly, more patients with infertility or PCOS experienced recurrence (P = 0.040, P = 0.015). Eight patients attempted to conceive after complete response; two spontaneous conceptions and one normal delivery were achieved. No disease-related or treatment-related deaths were observed. CONCLUSIONS: Fertility-sparing treatment with MA following entirely hysteroscopic curettage is effective, demonstrating the least toxicity for rigorously selected young women with well-differentiated EC confined to the endometrium or with AH; however, close follow-up is required for the potential consequences of improper patient selection and a substantial rate of recurrence.

Association between XPF polymorphisms and cancer risk: a meta-analysis.

BACKGROUND: Xeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: In this meta-analysis of 47,639 cancer cases and 51,915 controls, by searching three electronic databases (i.e., MEDLINE, EMBASE and CNKI), we summarized 43 case-control studies from 29 publications on four commonly studied polymorphisms of XPF (i.e., rs1800067, rs1799801, rs2020955 and rs744154), and we did not find statistical evidence of any significant association with overall cancer risk. However, in stratification analyses, we found a significant association of XPF-rs1799801 with a reduced cancer risk in Caucasian populations (4,845 cases and 5,556 controls; recessive model: OR=0.87, 95% CI=0.76-1.00, P=0.049, P=0.723 for heterogeneity test, I(2) =0). Further genotype-phenotype correlation analysis showed that the homozygous variant CC genotype carriers had higher XPF expression levels than that of the TT genotype carriers (Student's t test for a recessive model: P=0.046). No publication bias was found by using the funnel plot and Egger's test. CONCLUSION: This meta-analysis suggests a lack of statistical evidence for the association between the four XPF SNPs and overall risk of cancers. However, XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies.

A risk model for secondary cytoreductive surgery in recurrent ovarian cancer: an evidence-based proposal for patient selection.

BACKGROUND: To develop a risk model for predicting complete secondary cytoreductive surgery (SCR) in patients with recurrent ovarian cancer. METHODS: Individual data of 1075 patients with recurrent ovarian cancer undergoing SCR from 7 worldwide centers were pooled and analyzed. The risk model was developed based on the factors impacting on SCR surgical outcome. Additional data on 117 patients who were not included in the development of the model were used for external validation and to assess the discrimination of the model. RESULTS: Of the 1075 patients, 434 (40.4%) underwent complete resection. Complete secondary cytoreduction was associated with six variables: FIGO stage (odds ratio [OR] = 1.32, 95% confidence interval [95% CI]: 0.97-1.80), residual disease after primary cytoreduction (OR = 1.69, 95% CI: 1.26-2.27), progression-free interval (OR = 2.27, 95% CI: 1.71-3.01), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 2.23, 95% CI: 1.45-3.44), CA125 (OR = 1.85, 95% CI: 1.41-2.44), and ascites at recurrence (OR = 2.79, 95% CI: 1.88-4.13). These variables were entered into the risk model and assigned scores ranging from 0 to 11.9. Patients with total scores of 0-4.7 were categorized as the low-risk group, in which the proportion of complete cytoreduction was 53.4% compared with 20.1% in the high-risk group (OR = 4.55, 95% CI: 3.43-6.04). In external validation, the sensitivity and specificity was 83.3% and 57.6%, respectively. Area under the curve of the receiver-operating characteristics for predicting complete SCR was 0.68 (95% CI: 0.60-0.79). CONCLUSIONS: This model and scoring system may well predict the outcome of SCR and could potentially be useful in future clinical trials to determine which patients with recurrent ovarian cancer should have SCR as part of their management.

Surgery in recurrent epithelial ovarian cancer: benefits on Survival for patients with residual disease of 0.1-1 cm after secondary cytoreduction.

AIMS: Recent retrospective trials stated that a benefit of surgery for recurrent ovarian cancer may be limited to patients in whom a complete cytoreduction (R0) could be achieved. Most of them pointed out there was no difference in survival between residual disease of 0.1-1 cm (R1) and >1 cm (R2). The aim of this study was to evaluate survival benefits from cytoreduction to R1. METHODS: Between 2002 and 2006, 123 patients with recurrent epithelial ovarian cancer undergoing secondary cytoreduction were identified from tumor registry databases. RESULTS: The median age at recurrence was 51 years (range: 28-84). Fifty-one (41.5%) patients had R0, 46 (37.4%) patients had R1, and 26 (21.1%) patients had R2 resection. The median survival of the entire cohort was 31.7 months, with an estimated 5-year survival of 31.1%. The median survival and estimated 5-year survival for patients with R1 were 31.1 months and 23.9%, and there were significant differences in survival when compared to 15.6 months and 6.4% in R2 (chi(2) = 7.45, P = 0.006), 63.2 months (mean survival) and 54.4% in complete cytoreduction (chi(2) = 8.93, P = 0.0028). CONCLUSIONS: Complete secondary cytoreduction is the strongest survival determinant in recurrent epithelial ovarian cancer, whereas patients with residual disease of 0.1-1 cm may also benefit from secondary cytoreduction.

[Multidisciplinary therapy after radical surgery in stage I b1-II b cervical cancer patients with positive lymph nodes].

OBJECTIVE: To study the modality of multidisciplinary therapy and prognosis of cervical cancer patients with positive lymph nodes after radical surgery. METHODS: From January 1990 to June 2003, 215 patients with clinical stage I b1-II b node-positive cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy and were histologically confirmed to have lymph node involvement were analyzed. These patients were divided into four groups as chemoradiotherapy group (107 cases), radiotherapy group (45 cases), chemotherapy group (22 cases) and no adjuvant therapy group (41 cases). The prognosis and potential prognostic variables of the four groups were studied by survival analysis. RESULTS: The 3-year disease-free survival (DFS) rate of the chemoradiotherapy group, chemotherapy group, radiotherapy group and no adjuvant therapy group were 60.7%, 53.5%, 47.4% and 36.0% respectively. The 3-year DFS rate of the chemoradiotherapy group was significantly higher than that of the no adjuvant therapy group (P = 0.001). However, the 3-year DFS rate of the chemotherapy group, radiotherapy group were not significantly higher than that of the no adjuvant therapy group (P = 0.060 and 0.159). Among the four groups, the pelvic recurrent rate of the chemoradiotherapy group (7.5%) was much lower than those of the other three groups (22.7%, 26.7%, 34.1%, respectively; P < 0.01). However, the distant metastases rate did not decrease significantly (16.8%, 18.2%, 15.6%, 22.0%, respectively; P > 0.05), neither did the distant metastasis with pelvic recurrent rate (P > 0.05). COX proportional hazard model analysis showed that tumor size, histological type, the number of positive lymph node and postoperative adjuvant therapy were independent survival predictors of the patients with positive lymph node (P < 0.05). CONCLUSION: Chemoradiotherapy after radical surgery significantly improves the 3-year DFS, and decreases the pelvic recurrence in the cervical cancer patients with positive lymph node.

Recurrent ovarian carcinoma of low malignant potential: the role of secondary surgical cytoreduction and the prognosis in Chinese patients.

BACKGROUND AND OBJECTIVES: The study of pathology and prognosis for patients with ovarian tumors of low malignant potential (LMP) has been well documented. The treatment, particularly the secondary surgery, for recurrent disease is less documented. This study was conducted to investigate the role of secondary surgical cytoreduction for recurrent ovarian carcinoma of LMP. METHODS: Patients with ovarian carcinoma of LMP at advanced stages experiencing disease recurrence and treated by secondary surgical cytoreduction at Fudan University Cancer Hospital were retrospectively reviewed. RESULTS: Sixteen patients with recurrent serous and mucinous ovarian LMP tumors who underwent secondary surgical cytoreduction were entered in this study. The median age was 46.5 years. The 5-year survival in those with residual disease < or =1 cm after secondary surgical cytoreduction was 83%, compared to 26% in those with residual disease >1 cm (P = 0.01). Multivariate analysis suggested that extent of recurrent disease (solitary vs. multiple, relative risk [RR] =2.69, P < 0.01), and residual disease after secondary surgical cytoreduction (< or =1 cm vs. >1 cm, RR = 2.56, P < 0.01) were determinants of survival. CONCLUSIONS: For recurrent ovarian carcinomas of low malignant potential, prolonged survival was observed in patients with solitary recurrent disease and optimal secondary surgical outcome.

[Multidisciplinary treatment of recurrent epithelial ovarian carcinoma and prognostic analysis].

OBJECTIVE: To investigate individualized and multi-phase management of recurrent epithelial ovarian carcinoma in order to improve survival of the patients. METHODS: From 1998 to 2002, 70 patients with recurrent epithelial ovarian carcinoma were enrolled in the present study. The treatments were divided into: (1) Induction of tumor remission: platinum sensitive patients were treated with paclitaxol + cisplatin (TP) or carboplatin + cyclophosphamide (CP) regimen; platinum resistant patients used Taxol + mitomycin (TM) or etoposide + mitomycin (VM) regimen. Resection of tumors was done in an attempt to reduce the residual tumor with a diameter less than 1 cm. Local radiotherapy was performed for those with residual tumor and who achieved clinical response after chemotherapy or surgery. (2) Consolidation therapy: chemotherapy with lower doses was administrated after disease remission. Interferon was used as immunotherapy during chemotherapy and radiotherapy. Survival analysis was done. RESULTS: (1) The 1, 2, 3, 4, 5-year survival rates were 67%, 51%, 45%, 38%, 32%. Median survival was 38.57 months. (3) The 1, 2, 3-year progression-free survival rates of the research arm were 41%, 37%, 24%. Median progression-free survival was 12.00 months. (4) Multivariate analysis revealed that platinum-free interval (P < 0.05), Karnofsky performance scale (P < 0.01), residual disease (P < 0.01) and courses of second-line chemotherapy (P < 0.05) were independent prognostic factors. Residual disease (P < 0.05) and courses of second-line chemotherapy (P < 0.01) contributed to progression-free survival. CONCLUSIONS: Individualized and multi-phase treatment of recurrent epithelial ovarian carcinoma is efficacious. Optimal second cytoreduction and second-line chemotherapy are beneficial to improve the survival.

Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: who benefits?

BACKGROUND: This study was performed to address patient selection criteria and the role of secondary cytoreductive surgery (SCR) in patients with epithelial ovarian carcinoma (EOC) who had relapsed tumors after a progression-free interval > or = 3 months. METHODS: One hundred seventeen patients with relapsed EOC after a clinical complete remission duration > or = 3 months who underwent SCR were entered on this prospective trial. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using log-rank tests, logistic stepwise regression analyses, and a Cox stepwise regression model. RESULTS: The median patient age at the time of relapse was 53 years (range, 20-78 years). The median survival was 22 months and the estimated 5-year survival rate for the entire cohort was 17.2%. Tumor was confined to a solitary site in 33 patients and to > or = 2 sites in 84 patients. After they underwent SCR, 11 patients were rendered macroscopically disease free, 61 patients had residual disease that measured < or = 1 cm in greatest dimension, and 45 patients had bulky intraabdominal residual disease. Survival was influenced by the extent of relapse disease (solitary site vs. multiple sites; P < 0.0001), the size of residual disease after SCR (0 cm vs. < or = 1 cm [P = 0.1211], < or = 1 cm vs. > 1 cm [P = 0.0002], and 0 cm vs. > 1 cm [P = 0.0011]), Eastern Cooperative Oncology Group performance status (0 vs. 1 [P = 0.134], 1 vs. 2 [P = 0.007], and 0 vs. 2 [P = 0.0012]), and the number of cycles of salvage chemotherapy (1-2 cycles vs. 3-5 cycles [P = 0.0144]; 1-2 cycles vs. > or = 6 cycles [P < 0.0001]; and 3-5 cycles vs. > or = 6 cycles [P = 0.0009]). The outcome of SCR was influenced by the extent of relapse disease (multiple sites [51.2%] vs. solitary sites [87.9%]; relative risk [RR] = 9.1237; P = 0.0002) and by the use of bowel resection (yes [60.9%] vs. no [37.5%]; RR = 0.3828; P = 0.0106). CONCLUSIONS: SCR was found to be safe for patients with relapsed EOC who achieved a clinical complete remission that lasted > or = 3 months, with resectability similar to that of primary debulking surgery. Optimal surgical outcomes were achieved easily in patients who apparently had solitary tumor sites, with bowel resection making it possible to remove bulky tumors that involved the intestine. A survival benefit was provided by optimal SCR, particularly when surgery was supported by multiple courses of salvage chemotherapy.

[Prognosis of patients with stage Ib-IIb node-positive cervical carcinoma].

BACKGROUND & OBJECTIVE: Pelvic lymph node metastasis was the important prognostic factor for the patients with cervical carcinoma. However, the relationship among the number of positive nodes, site of metastatic nodes, adjuvant therapy, and the prognosis were unknown. The purpose of this study was to investigate the variables that could predict the prognosis of the patients with stage Ib-IIb node-positive cervical carcinoma. METHODS: Sixty-six patients with stage Ib-IIb cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy were analyzed retrospectively. Potential prognostic variables were studied by Cox proportional hazard model. RESULTS: The 5-year survival rate of the patients with pelvic lymph node metastasis was 40.7%. Cox proportional hazard model analysis showed cellular differentiation, number of positive nodes, and adjuvant therapy were the important prognostic factors (P< 0.05). The 5-year survival rate of patients with one positive node (56.5%) was higher than that (36.4%) of those with two or more positive nodes (P< 0.05). The former's distant metastatic rate (5.9%) was lower than the latter's (32.7%) (P=0.05). However, there was no difference of pelvic recurrence between them (P >0.05). The 5-year survival rate of the patients who had no adjuvant therapy (12.6%) was much lower than that (53.7%) of those with adjuvant therapy (P< 0.05). However, the differences of the effects among adjuvant radiotherapy, chemotherapy, and chemoradiotherapy were not obvious (P >0.05). CONCLUSION: The prognosis of patients with stage Ib-IIb node-positive cervical carcinoma who underwent radical surgery was poor. Adjuvant therapy can improve the survival rate, decrease the pelvic recurrence and distant metastasis.

[Significance of systematic retroperitoneal lymphadenectomy at second-look laparotomy for ovarian cancer].

OBJECTIVE: To investigate the timing and role of systemic retroperitoneal lymphadenectomy in patients with ovarian cancer. METHODS: From Jan. 1987 to Feb. 1994, 50 patients with ovarian cancer, who underwent retroperitoneal lymphadenectomy on second-look laparotomy (SLL), were retrospectively studied. RESULTS: The median age was 49 years. Overall survival at 3 and 5 years were 72% and 62%, respectively. Twenty of 50 (40%) women were found SLL(+), and the rates of positive SLL were related to International Federation of Gynecology Obstetrics (FIGO) stage, with 16% in stage I and II, 64% in stage III and IV (P < 0.01). Sixteen (32%) women were found to have retroperitoneal lymph nodes metastases at SLL, with 0% (0/15), 20% (2/10), 54% (13/24), 1/1 in stage I, II, III, IV respectively. In patients with SLL(+), 4 patients with sole disease in the pelvis, and 6 (12%) women only with micro-metastases of retroperitoneal lymph nodes. Fifteen patients with stage I ovarian cancer were all SLL(-), and SLL(-) were in 6 (60%) patients with stage II disease and 11 (38%) in stage III. There is no disease recurrence in patients with negative SLL till the data censored. CONCLUSION: Timing of systemic retroperitoneal lymphadenectomy at SLL is rational, and may aid in reducing disease recurrence of negative SLL and improving five-year survival rate in patients with ovarian cancer, especially in those with advanced epithelial ovarian cancer.