Prognostic factors of secondary cytoreductive surgery for patients with recurrent epithelial ovarian cancer

Objective

The objective of this study was to identify the prognostic factors of secondary cytoreductive surgery on survival in patients with recurrent epithelial ovarian cancer.

Methods

The medical records of all patients who underwent secondary cytoreductive surgery between May 2001 and October 2007 at the National Cancer Center, Korea were reviewed. Univariate and multivariate analyses were executed to evaluate the potential variables for overall survival.

Results

In total, 54 patients met the inclusion criteria. Optimal cytoreduction to <0.5 cm residual disease was achieved in 87% of patients who had received secondary cytoreductive surgery. Univariate analysis revealed that site of recurrence (median survival, 53 months for the largest tumors in the pelvis vs. 24 months for the largest tumors except for the pelvis; p=0.007), progression free survival (PFS) (median survival, 43 months for PFS≥12 months vs. 24 months for PFS<12 months; p=0.036), and number of recurrence sites (median survival, 49 months for single recurred tumor vs 29 months for multiple recurred tumors; p=0.036) were significantly associated with overall survival. On multivariate analysis, prognostic factors that correlated with improved survival were site of recurrence (p=0.013), and PFS (p=0.043).

Conclusion

In the author''s analysis, a significant survival benefit was identified for the recurred largest tumors within the pelvis and PFS≥12 months. Secondary cytoreductive surgery should be offered in selected patients and large prospective studies are needed to define the selection criteria for secondary cytoreductive surgery.     

Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma

BACKGROUND: The benefit of cytoreductive surgery for patients with recurrent epithelial ovarian cancer has not been defined clearly. The objective of this study was to identify prognostic factors for survival in patients who underwent secondary cytoreduction for recurrent, platinum-sensitive epithelial ovarian cancer and to establish generally applicable guidelines and selection criteria. METHODS: The authors reviewed all patients who underwent secondary cytoreduction for recurrent epithelial ovarian cancer from 1987 to 2001. Potential prognostic factors were evaluated in univariate and multivariate analyses. RESULTS: In total, 157 patients underwent secondary cytoreduction, and 153 of those patients were evaluable. After secondary cytoreduction, the median follow-up was 36.9 months (range, 0.2-125.6 months), and the median survival was 41.7 months (95% confidence interval, 36.0-47.2 months). For patients who had a disease-free interval prior to recurrence of between 6 months and 12 months, the median survival was 30 months compared with 39 months for patients who had a disease-free interval between 13 months and 30 months and 51 months for patients who had a disease-free interval >30 months (P = .005). For patients who had a single site of recurrence, the median survival was 60 months compared with 42 months for patients who had multiple sites of recurrence and 28 months for patients who had carcinomatosis (P <.001). The median survival for patients who had residual disease that measured < or =0.5 cm was 56 months compared with 27 months for patients who had residual disease that measured >0.5 cm (P <.001). On multivariate analysis, disease-free interval (P = .004), the number of recurrence sites (P = .01), and residual disease (P <.001) were significant prognostic factors. CONCLUSIONS: In the authors' analysis of secondary cytoreduction for recurrent epithelial ovarian cancer, a significant survival benefit was demonstrated for residual disease that measured < or = 0.5 cm. The disease-free interval and the number of recurrence sites should be used as selection criteria for offering secondary cytoreduction.     

复发性卵巢上皮癌二次肿瘤细胞减灭术研究进展

对于复发性卵巢上皮癌患者采用二次肿瘤细胞减灭术（STRS）及后续药物治疗能延长生存期,提高生活质量,手术范围以最大限度切除复发灶为原则,STRS后残存肿瘤的大小足影响预后的主要因素。现综述复发性卵巢上皮癌STRS的类型和适应证、手术方式及临床价值。     

复发性卵巢上皮癌二次肿瘤细胞减灭术研究进展

对于复发性卵巢上皮癌患者采用二次肿瘤细胞减灭术(STRS)及后续药物治疗能延长生存期,提高生活质量,手术范围以最大限度切除复发灶为原则,STRS后残存肿瘤的大小是影响预后的主要因素。现综述复发性卵巢上皮癌STRS的类型和适应证、手术方式及临床价值。     

The role of secondary cytoreductive surgery for recurrent mucinous epithelial ovarian cancer (mEOC)

Background

Mucinous epithelial ovarian cancer (mEOC) may exhibit a distinct biological behavior in epithelial ovarian cancer (EOC). The role of secondary cytoreductive surgery was evaluated in patients with recurrent mEOC, and the prognosis was assessed.

Methods

Twenty-one patients with stages IIc to IV mEOC who experienced disease recurrence and received secondary cytoreductive surgery at Fudan University Cancer Hospital between Jan. 1997 and Dec. 2005 were retrospectively reviewed. Survival curves were generated using the Kaplan–Meier method and the significant comparison of survival rate was estimated by the log-rank test.

Results

The median progression-free interval (PFI) was 14 months (range, 5–46 months) after the first cytoreduction. Seven patients (33%) who received secondary cytoreductive surgery were optimally cytoreduced with residual disease less than or equal 1 cm, and the other 14 patients (67%) underwent suboptimal surgical cytoreduction. The overall median survival time was 27 months (range, 8–64 months). The median survival time after recurrence was 10 months (range, 3–32 months). There was no significant statistical difference in median survival between patients with optimal and suboptimal secondary surgical cytoreduction, with an estimated survival of 10 months and 9.8 months, respectively (P > 0.05).

Conclusion

Optimal primary cytoreductive surgery for advanced mEOC was very important. Once it recurs, the prognosis is very poor. Patients with recurrent mEOC should be carefully assessed before performing secondary cytoreductive surgery, as this may have limited impact on the overall survival rates.     

Secondary cytoreductive surgery for recurrent epithelial ovarian carcinoma: proposal for patients selection

The value of secondary cytoreductive surgery (SCS) for recurrent ovarian cancer is still controversial. The aim of this study was to clarify candidates for SCS. Between January 1987 and September 2000, we performed SCS in 44 patients with recurrent ovarian cancer, according to our selection criteria, disease-free interval (DFI) >6 months, performance status <3, no apparent multiple diseases, age <75 years and no progressive disease during preoperative chemotherapy, if undertaken. The variables were investigated by univariate and multivariate analyses. Of 44 patients, 26 (59.1%) achieved complete removal of all visible tumours at SCS. Secondary cytoreductive surgery outcome, complete or incomplete resection, was significantly related to overall survival (P=0.0019). As for variables determined before SCS, DFI >12 months, no liver metastasis, solitary tumour and tumour size <6 cm were independently associated with favourable overall survival after recurrence in the multivariate analysis. Patients with three or all four variables (n=31) had significantly better survival compared with the other patients (n=13) (47 vs 20 months in median survival, P<0.0001). In these patients, fairly good median survival (40 months) was obtained even in patients with incomplete resection. Secondary cytoreductive surgery had a large impact on survival of patients with recurrent ovarian cancer when they had three or all of the above-mentioned four factors at recurrence. These patients should be considered as ideal candidates for SCS.     

The role of secondary cytoreductive surgery in patients with recurrent epithelial ovarian, tubal, and peritoneal cancers: a comparative effectiveness analysis

Background. All published reports concerning secondary cytoreductive surgery for relapsed ovarian cancer have essentially been observational studies. However, the validity of observational studies is usually threatened from confounding by indication. We sought to address this issue by using comparative effectiveness methods to adjust for confounding. Methods. Using a prospectively collected administrative health care database in a single institution, we identified 1,124 patients diagnosed with recurrent epithelial, tubal, and peritoneal cancers between 1990 and 2009. Effectiveness of secondary cytoreductive surgery using the conventional Cox proportional hazard model, propensity score, and instrumental variable were compared. Sensitivity analyses for residual confounding were explored using an array approach. Results. Secondary cytoreductive surgery prolonged overall survival with a hazard ratio (95% confidence interval) of 0.76 (range 0.66-0.87), using the Cox proportional hazard model. Propensity score methods produced comparable results: 0.75 (range 0.64-0.86) by nearest matching, 0.73 (0.65-0.82) by quintile stratification, 0.71 (0.65-0.77) by weighting, and 0.72 (0.63-0.83) by covariate adjustment. The instrumental variable method also produced a comparable estimate: 0.75 (range 0.65-0.86). Sensitivity analyses revealed that the true treatment effects may approach the null hypothesis if the association between unmeasured confounders and disease outcome is high. Conclusions. This comparative effectiveness study provides supportive evidence for previous reports that secondary cytoreductive surgery may increase overall survival for patients with recurrent epithelial, tubal, and peritoneal cancers.     

Effect of cytoreductive surgery on survival of patients with recurrent epithelial ovarian cancer

BACKGROUND AND OBJECTIVES: The value of secondary cytoreductive surgery is still controversial, especially in patients with recurrent epithelial ovarian cancer. In this retrospective study, we investigated the effect on survival of secondary cytoreduction for recurrent disease and variables influencing redebulking surgical outcome. METHODS: Between 1986 and 1997, 60 patients who received primary cytoreductive surgery and platinum-based chemotherapy for stage III and IV epithelial ovarian cancer experienced disease recurrence at least 6 months after completion of primary therapy, and secondary surgical cytoreduction was performed. The optimal residual disease cutoff was 1.0 cm. The Cox proportional regression model and Logistic stepwise regression were used in statistical processing of the data. RESULTS: The median progression-free interval between the two operations was 13 months (range, 6-56 months). Optimal secondary cytoreduction was achieved in 23 patients (38.33%). There was a significant difference in survival between patients who were optimally cytoreduced compared to those suboptimally cytoreduced, with an estimated median survival in the optimal group of 19 months vs. 8 months in the suboptimal group (chi(2) = 22.04, P = 0.0000). Prognosis of survival for individuals with progression-free interval >12 months was better than that of those with the interval 1.0 cm after primary operation should be considered prudently.     

提高复发性卵巢上皮癌手术切除率的探讨

背景与目的:复发性卵巢上皮癌能否手术切除对预后影响较大,提高复发性卵巢上皮癌的手术切除率有助于改善其预后。本研究旨在探讨如何提高复发性卵巢上皮癌的手术切除率。方法:回顾性分析1997年3月1日至2003年3月31日期间因复发性卵巢上皮癌在我院行第二次细胞减灭术的54例病例的临床资料。其中病灶部位局限于盆腔19例,超出盆腔35例。病灶数目为1个者16例,≥2个者38例。无腹水38例,有腹水16例。接受术前化疗20例,有效12例,无效8例。以 Logistic多因素回归,分析年龄、复发间隔时间、复发病灶部位、数目、有无腹水及复发术前化疗对复发术后残留灶的影响。结果:肿瘤的满意切除率为81.5％(44/54),其中无残留灶者占53.7％(29/54),残留灶≤2 cm者占27.8％(15/54)。Logistic分析显示,病灶部位及有无腹水是影响复发术后残留灶的显著性因素(P<0.05);复发术前化疗有效和无效患者的满意切除率分别为100％(12/12)和37.5％(3/8),卡方检验显示两者有非常显著性差异(P<0.01)。本组40.7％(22/54)的患者手术较复杂,涉及胃肠道、泌尿道或肝脾。术后并发症发生率为16.6％(9/54),手术死亡率1.9％(1/54)。结论:根据患者瘤灶的边界、部位、有无腹水及术前化疗的疗效,对复发患者进行适当的选择,并作好充分的术前准备有助于提高复     

二次肿瘤细胞减灭术治疗复发性卵巢癌的研究进展

二次肿瘤细胞减灭术（secondary cytoreductive surgery,SCS）作为复发性卵巢癌的治疗方法之一,以完全切除肿瘤,使残留病灶达到最小为目标,主要适用于铂敏感性复发性上皮性卵巢癌(epithelial ovarian cancer,EOC)的治疗。这种再次手术切除肿瘤病灶的方式与传统治疗方式相比,能否改善复发性卵巢癌患者生存和预后,给患者带来新的希望,目前没有确切结论。术前准确预测SCS的效果,选择更适合进行SCS的复发性卵巢癌患者,分析影响SCS预后的因素,可以使SCS更好地应用于复发性卵巢癌的治疗。本文对SCS治疗复发性卵巢癌的适应证、手术方法以及预后影响因素进行综述。     

卵巢癌二次细胞减灭术和二线化疗疗效分析

目的 :对铂类化疗效果不佳或缓解后复发的卵巢癌再次治疗的疗效和生存的因素分析。方法 :50例平均停用铂类药物化疗时间 (PFI)为 6 .6(0 .5～ 36)月的卵巢癌患者接受二次肿瘤细胞减灭术及术后二线化疗。结果 :二次减灭术有 33例达到满意减瘤状态 (术后残瘤≤ 1cm) ,PFI≤ 6月 1 9例。患者术后平均接受 4次 (1～ 1 1次 )的二线静脉化疗 ,其中用Taxol化疗 1 5例 ,用铂类联合化疗 35例。CR 1 8例 ,PR 2例。Logistic回归分析结果提示腹水 (P =0 .0 2 2 3)、残瘤大小 (P =0 .0 2 4 7)和化疗次数 (P =0 .0 4 97)是决定卵巢癌二线化疗效果的重要因素。行满意的再次减灭术者中位生存期达 42 .3月 ,明显高于残瘤较大患者的 1 4 .2月 (χ2 =1 3 .62 ,P =0 .0 0 0 2 )。有腹水者存活期短于无腹水者 ,两者的中位生存期分别为 1 4 .2月和 2 8.9月 (χ2 =5 .38,P =0 .0 2 0 3)。二线化疗次数大于 5次以上则生存期延长 ,中位生存期 31 .0月 ,不超过 5次的为 1 6 .5月 (χ2 =1 3 .0 5 ,P =0 .0 0 0 3)。PFI >6月者生存期达 42 .3月 ,比PFI≤ 6月者 1 7.5月长 ,但无统计学意义 (P =0 .1 4 1 8)。多因素分析结果提示PFI和化疗次数是影响卵巢癌再次治疗的独立的预后因素。对PFI≤ 6月者 ,二次手术后残余肿瘤≤ 1cm者二次手     

Impact of secondary cytoreductive surgery on survival of patients with advanced epithelial ovarian cancer

Aims To investigate the impact on survival of secondary cytoreduction for advanced epithelial ovarian cancer and variables influencing redebulking surgical outcome. Methods Between 1986 and 1997, 106 patients who received secondary cytoreductive surgery and consequent second-line chemotherapy for stages III and IV epithelial ovarian cancer were retrospectively reviewed. The optimal residual disease cut-off was 1.0 cm. The Cox proportional regression model and logistic stepwise regression were used in statistical processing of the data. Results The median age of the patients was 50 years (range, 26–77 years). Optimal secondary cytoreduction was achieved in 46 of 106 patients (43.4%). There was a significant difference in survival between patients who were optimally cytoreduced compared to those suboptimaly cytoreduced, with an estimated median survival in the optimal group of 20 months vs 8 months in the suboptimal group (²=42.03, P=0.0000). When factorized, patients had significant survival benefit from optimal secondary cytoreduction for recurrent disease and interval cytoreduction. Survival was adversely influenced by progression-free interval ≤12 months (P=0.0078), residual disease >1 cm (P=0.0001) and presence of refractory ascites (P=0.0001). The probability of successful redebulking surgery was affected by presence of refractory ascites (P=0.0023) in all 106 patients and by the ascites (P=0.0072) and residual disease at initial operation in recurrent disease (P=0.0096). Conclusion Secondary surgical cytoreduction surgery significantly lengthened survival for patients with recurrent epithelial ovarian cancer or those receiving interval cytoreduction. Patients with refractory ascites, however, were not suitable for aggressive secondary surgery, and redebulking surgery for those with residual disease of >1.0 cm after primary operation should be considered prudently in recurrent disease.     

Primary cytoreductive surgery with rectosigmoid colon resection for patients with advanced epithelial ovarian carcinoma

BACKGROUND: The impact of radical bowel resection with multiple organ resection on the survival if patients with advanced ovarian carcinoma has not been well defined. The authors investigated whether primary cytoreductive surgery including rectosigmoid colon resection would affect the recurrence free interval and survival of these patients. METHODS: Between April 1990 and April 1997, 66 previously untreated Stage IIIC-IV ovarian carcinoma patients with macroscopic involvement of the rectosigmoid colon were enrolled. All patients underwent cytoreductive surgery with rectosigmoid colon resection to remove residual tumor less than 2 cm in greatest dimension and received 6 cycles of cisplatin-based postoperative chemotherapy. RESULTS: The median follow-up was 26 months (range, 7-104 months). In multivariate analysis, residual disease and depth of tumor infiltration of the bowel wall were independently associated with overall survival and recurrence free interval. Disease stage was independently associated only with overall survival. Residual tumor was the most strongly predictive factor for recurrence or death. The 2-year estimated survival rates according to the amount of residual tumor were 100% for 24 patients with no macroscopic residual disease and 77.3% for 28 patients with residual disease less than 1 cm. None of the 14 patients with residual disease larger than 1 cm were alive 2-years after operation. Overall, 48 patients (72.7%) developed disease recurrence: 43 (65.1%) in the abdomen, 19 (29.8%) in the liver, and 3 (4.5%) in the pelvis. CONCLUSIONS: The current findings suggest that cytoreductive surgery with rectosigmoid colon resection should be considered for ovarian carcinoma patients with bulky pelvic disease to help ensure that they are left with no residual disease after debulking surgery.     

Timing of surgery and the role of cytoreductive chemotherapy in patients with advanced ovarian carcinoma

We retrospectively selected 27 consecutive patients with advanced ovarian carcinoma (15 stage III, 11 stage IV and 1 relapse) who had an unresectable intraabdominal tumor at presentation and prospectively evaluated the overall treatment outcome. Patients were initially treated with chemotherapy consisting of cisplatin-containing regimens in 20 cases, adriamycin and cyclophosphamide in 5, and melphalan in 2. Treatment was continued until maximal tumor response or progression. Following a median of 6 cycles of chemotherapy, all patients underwent debulking surgery. Six women were without evidence of disease and 13 had minimal residual disease after surgery, for an overall 70% rate of optimal debulking. Patients with evidence of disease at laparotomy were treated with 5 additional cycles of chemotherapy, and response was then assessed at laparotomy except for patients with progressive disease. Nine (33%) patients were pathologic complete responders at the end of the entire treatment program. Overall median survival time was 26 months, with a median relapse-free survival of 33 months. Tumor responses were not associated with any particular chemotherapy regimen. The results achieved in this series of patients together with the data from the literature suggests that use of a cytoreductive chemotherapy of short duration has the potential of increasing the rate of optimal debulking surgery. Furthermore, it may contribute to a better disease control in women with bulky ovarian carcinoma compared to the present strategy, which consists of surgery followed by chemotherapy.     

复发性卵巢上皮癌二次细胞减灭术的临床意义

目的 探讨复发性卵巢上皮癌二次细胞减灭术（SCR）的作用及其影响因素。方法 60例晚期卵巢上皮癌因肿瘤复发行SCR治疗。采用Cox逐步回归分析预后的影响因素;采用Logistic回归分析影响SCR的危险因素。结果 SCR术后残癌≤1cm组与＞1cm组的中位生存期分别为19个月和8个月,差异有显著性（P＝0.0000)。缓解期＞12个月与≤12个月者,再手术后中位生存期分别为12个月和8个月,差异有显著性（P＝0.0224)。肿瘤复发伴有腹水是预后的影响因素,同时也是影响SCR的主要危险因素。复发伴腹水者,SCR切净的可能减少了20．36倍。第1次手术后残癌＞1cm是影响SCR的危险因素（RR＝5．16）。本组手术死亡率1．7％,术后并发症发生率8．3％。结论 在有效二线化疗的配合下,SCR对首次行满意细胞减灭术、缓解期达12个月以上、无腹水的复发性卵巢上皮癌患者有肯定的临床疗效。     

Proposal for selection criteria of secondary cytoreductive surgery in recurrent epithelial ovarian,tubal, and peritoneal cancers

Background

The selection criteria for secondary cytoreductive surgery (SCS) in recurrent ovarian cancer are yet to be defined. The aim of this study was to propose the selection criteria through identifying predictive factors for successful SCS.

Methods

All patients who underwent SCS for recurrent epithelial ovarian, tubal, and peritoneal cancers between 1982 and 2012 at our institution were identified through our database. Potential prognostic factors were evaluated in univariate and multivariate analyses. Survival after SCS was examined by the grouping model based on the number of prognostic factors.

Results

We performed SCS in 80 consecutive patients, 48 (60 %) of whom achieved complete resection. Complete/incomplete resection significantly influenced survival (median 65 vs. 26 months; p = 0.0005). Among favorable prognostic factors determined before SCS, treatment-free interval >12 months, absent distant metastasis, solitary disease, and performance status 0 were independently associated with better survival (p = 0.0009, 0.00003, 0.0004, and 0.015, respectively). Patients with 3–4 of those factors had better survival than those with 2 or 0–1 factors (median 79, 26, and 19 months; p < 0.00001 and <0.0000000001, respectively). Complete resection of visible tumors was achieved in 79 % of patients with 3–4 factors, in 40 % of those with 2 factors, and in 33 % of those with 0–1 factor. Importantly, even when tumor removal was incomplete at SCS, median survival of patients with 3–4 factors was still quite favorable (83 vs. 67.5 months for complete/incomplete resection, respectively), while those of patients with 2 factors (41 vs. 25 months) and 0–1 factor (19 vs. 19 months) were not.

Conclusion

We strongly recommend SCS for patients with 3–4 of the above favorable factors at recurrence. As for patients with 2 factors, SCS may be considered if complete resection is expected to be achieved. Prospective studies are warranted to validate our proposal.

     

Role of cytoreductive surgery in recurrent ovarian cancer

Cytoreductive surgery is well established in patients with primary ovarian cancer. The benefit of surgery in patients with recurrent ovarian cancer remains a controversial matter. There is a large heterogeneity in surgical results published in the literature, possibly caused by infrastructure, surgeons’ philosophy and belief in adding various surgical skills. This might also be a result of different preoperative selection procedures. Further questions to be addressed are the definition of surgical end points and whether there are predictive factors for a successful surgery. The surgical end point in recurrent ovarian cancer should be complete resection. Predictive factors could help identify patients in whom complete resection is possible.