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.     

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.     

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.     

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     

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.     

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.     

上皮性卵巢癌初次肿瘤细胞减灭术后复发情况及影响因素分析

目的:研究上皮性卵巢癌初次肿瘤细胞减灭术后复发情况以及影响因素分析,旨在为降低上皮性卵巢癌初次肿瘤细胞减灭术后复发提高患者术后生存质量提供有效的理论依据。方法:采用回顾性方法分析我院在2008年1月至2012年12月期间进行肿瘤细胞减灭术治疗的186例上皮性卵巢癌患者的临床资料,术后根据患者复发情况将患者分成复发组与未复发组。观察两组患者年龄、组织学类型、化疗方式、新辅助化疗、临床分期、组织分级、残余病灶、腹水、术前HE4、术后2月CA125、淋巴结切除之间的差异,同时分析影响上皮性卵巢癌初次肿瘤细胞减灭术后复发的独立危险因素。结果:随访5年,复发患者有78例,复发率为41.94%,未复发患者108例;复发组与未复发组患者在年龄、组织学类型、化疗方式、新辅助化疗等因素中比较无差异（P＞0.05）,在临床分期、组织分级、残余病灶、腹水、术前HE4、术后2月CA125、淋巴结切除中存在明显差异（P＜0.05）;经Logistic回顾分析证明,临床分期、残余病灶、腹水、术前HE4、淋巴结切除是临床上皮性卵巢癌患者初次肿瘤细胞减灭术后复发的独立危险因素［OR=9.786（3.484~27.493）、OR=8.199（4.431 ~15.172）、OR=9.143（3.975~21.031）、OR=9.337（4.593~18.983）、OR=11.917（6.440~22.053）］。结论:上皮性卵巢癌患者经初次肿瘤细胞减灭术治疗后,复发率为41.94%左右,而影响患者术后复发的独立危险因素为临床分期、残余病灶、腹水、术前HE4、淋巴结切除等,临床上可针对这些因素进行干预降低临床术后复发率,提高患者生活质量。     

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。     

Secondary cytoreductive surgery for isolated lymph node recurrence of epithelial ovarian cancer: A multicenter study

Introduction

Chemotherapy is the standard treatment of recurrent epithelial ovarian cancer (EOC), but its use in nodal relapses is still debated. On the other hand, the role of secondary cytoreductive surgery (SCS) remains controversial. Aim of this study is to evaluate feasibility and outcomes of SCS for the specific setting of recurrent ovarian cancer, exclusively relapsing in lymph nodes.

Patients and methods

We conducted a retrospective analysis in five Italian Institutions (University of Torino, INT of Milano, CRO of Aviano, University of Pisa and INT of Napoli) from 2000 to 2012. Patients with EOC who underwent secondary surgery for isolated lymph node recurrence (ILNR) were selected.

Results

Seventy-three patients were identified. At first diagnosis, patients received debulking surgery and platinum-based chemotherapy. The median disease free interval from completion of primary chemotherapy to nodal recurrence was 18 months. Nodal recurrence was para-aortic in 37 patients (50.7%), pelvic in 21 (28.8%), pelvic and para-aortic in 9 (12.3%), pelvic and inguinal in 3 (4.1%) and inguinal in 3 (4.1%). During SCS, in 1 patients nephrectomy was necessary for renal vein injury. No significant postoperative morbidity occurred. Median follow-up is 50 months. After secondary surgery, 32 (43.8%) are alive without disease, 18 (24.6%) are alive with disease and 23 patients (31.5%) are dead of disease. Five-year overall survival from the time of treatment of recurrent disease is 64%.

Conclusions

Secondary surgery for ILNR of ovarian cancer is feasible, safe, with low morbidity and it is associated with a favorable outcome.     

Secondary cytoreductive surgery for localized, recurrent epithelial ovarian cancer: analysis of prognostic factors and survival outcome

BACKGROUND: The objective of this study was to evaluate the role of secondary cytoreductive surgery in the outcome of patients who had recurrent epithelial ovarian carcinoma that was limited to or=12 months between initial diagnosis and recurrence, and or=18 months (median survival, 49 months vs 3 months; P < .01), the number of radiographic recurrence sites (median survival, 50 months for patients with 1 or 2 sites vs 12 months for patients with 3 to 5 sites; P < .03), and residual disease (median survival, 50 months for patients with no macroscopic residual disease vs 7.2 months for patients with macroscopic residual disease; P < .01). Age, tumor grade, histology, CA-125 level, ascites, and tumor size were not associated significantly with survival. CONCLUSIONS.: The current data supported the definition of localized recurrent ovarian cancer as patients with 1 or 2 radiographic recurrence sites. In this select population, a diagnosis-to-recurrence interval >or=18 months and complete secondary surgical cytoreduction, which was achievable in the majority of patients, were associated with a median postrecurrence survival of approximately 50 months.     

紫杉醇治疗复发卵巢上皮癌31例临床疗效观察

目的比较紫杉醇为主的联合化疗在治疗复发卵巢上皮癌时,紫杉醇周疗与月疗不同给药方法的近期疗效、复发后生存时间及毒副作用。方法回顾性分析1997年1月至2004年12月期间我科用紫杉醇联合化疗的31例复发性卵巢上皮癌患者。紫杉醇周疗组14例紫杉醇60mg/m2静脉滴注每周1次,连续3周为1周期。月疗17例,紫杉醇135mg/m2静脉滴注3周1次为1周期。铂类等药用法两组相同顺铂70mg/m2,或卡铂300mg/m2或AUC=4~5,或奥沙利铂100mg/m2静脉滴注d2,均3周重复1次。结果全组31例病人均可进行近期疗效评价,总有效率为38.71%。周疗组和月疗组的有效率分别为42.86%(6/14)和35.29%(6/17)。随访的26例病例中,中位生存时间22个月。周疗组和月疗组中位生存时间分别是26.5个月、20个月。紫杉醇的毒副作用以白细胞下降、恶心呕吐、肌肉关节痛、手足麻木、脱发等常见。两组间毒副作用的发生率无明显差异,但周疗组毒副作用发生程度较低。结论紫杉醇无论对铂类敏感或对铂类耐药的复发卵巢上皮癌病例,均有较高的疗效,是复发卵巢癌的首选药物。紫杉醇周疗与月疗治疗复发卵巢上皮癌的近期疗效相近,而紫杉醇周疗在降低药物毒副作用、改善患者生存质量、延长生存时间方面比紫杉醇月疗更好。     

Ⅲ期卵巢癌减灭术后腹腔残瘤对患者预后的影响

目的：分析Ⅲ期卵巢癌减灭术后腹腔残瘤对患者预后的影响因素。方法：1990年11月～1996年11月本院行初次肿瘤细胞减灭术的Ⅲ期卵巢癌57例，平均年龄51．9岁(23～74岁)。术后肉眼无残瘤9例，腹腔残瘤7例，盆腔残瘤4例，腹盆腔均有残瘤37例，残瘤≤1cm的20例。术前有30例接受化疗，术后腹腔化疗36例，平均3次，术后铂类为主静脉化疗46例，平均4次。治疗后临床完全缓解32例(56．1％)。结果：平均随访29．1月(0．3～109．1月)，Ⅲ期卵巢癌的一年、二年、三年、四年、五年生存率分别为79．82％，57．59％，49．06％，39．93％，23．41％。单因素分析发现分期(P=0．0283)、残瘤大小(P=0．0041)、腹腔残瘤(P=0．0362)、手术方式(P=0．0337)、术后腹腔化疗(P=0．0469)等因素均影响患者术后生存。多因素分析结果提示残瘤大小(P=0．0025)、术后腹腔化疗(P=0．0323)和静脉化疗(P=0．0297)是影响患者生存的独立的预后因素。术后腹腔内肉眼无残瘤者的存活率高于腹腔有残留者，中位生存期分别为58．0月和22．7月(P=0．0362)，三年、五年生存率分别为83．64％vs37．60％，29．57％vs21．05％。对于术后腹腔内肉眼有残瘤者，腹腔内残瘤小者生存期较长(P=0．0319)，盆腔内残瘤大小影响患者无瘤生存期(P=0．0104)。分期(P=0．041)、术前化疗(P=0．009)和病理类型(P=0．042)影响术后腹腔有无肿瘤残余。结论：术后腹腔残瘤和残余肿瘤大小影响Ⅲ期卵巢癌患者的生存。腹腔内有肿瘤残留者预后差，上腹部残余肿瘤影响患者生存，盆腔残余肿瘤则影响患者无瘤生存。     

First-line treatment for advanced ovarian cancer: paclitaxel,platinum and the evidence

Four large randomised trials of paclitaxel in combination with platinum against a platinum-based control treatment have now been published in full, representing around 88% (3588 out of 4057) of patients randomised into the eight known trials of this question. There is substantial heterogeneity in the results of these four trials. Four main explanations for this heterogeneity have been proposed: differences in the extent and timing of 'crossover' to taxanes in the control groups; differences in the types of patient included; differences in the effectiveness of the research regimens used; differences in the effectiveness of the control regimens used. In this study we examine whether any of these explanations is consistent with the pattern of results seen in these trials. Each explanation suggests that a particular characteristic of each trial was responsible for the results observed. For each explanation the trials were split into groups according to that characteristic, in order to partition the total heterogeneity into that seen 'within' and 'between' groups of trials. If a particular explanation was consistent with the pattern of results, we would expect to see relatively little heterogeneity within each group of trial results viewed in this way, with most of the heterogeneity being between groups which are dissimilar with respect to the key characteristic. Heterogeneity 'within' and 'between' groups was formally compared using the F-ratio. If any explanation appeared to be consistent with the results of the trials, it was considered whether the explanation was also consistent with other evidence available about these regimens. Only one explanation appeared to be consistent with the pattern of results seen in these trials, and that was differences in effectiveness of the control arms used in these trials. This suggests that the very positive results in favour of paclitaxel/cisplatin seen in two of the trials may have been due to the use of a suboptimal control arm. There is no direct evidence about the relative effectiveness of the control arms used in these trials, but indirect evidence is consistent with the conclusion that the cyclophosphamide/cisplatin regimen used in two of the trials may be less effective than the control regimens used in the other trials. Specific concerns about the choice of a cyclophosphamide/cisplatin control arm in the first of these trials to report were raised before the results of the other trials were known, i.e. before any heterogeneity had been observed. Further investigation of this question would be useful. In the meantime, given all of the randomised evidence on the efficacy and toxicity associated with the regimens used in these trials, we conclude that single agent carboplatin is a safe and effective first-line treatment for women with advanced ovarian cancer.     

白蛋白结合型紫杉醇治疗复发性上皮性卵巢癌及原发性腹膜癌的回顾性研究

目的 探讨白蛋白结合型紫杉醇（ABX）治疗复发性上皮性卵巢癌及原发性腹膜癌患者的疗效及耐受性。方法 对2010年1月至2012年11月在我院接受ABX为基础化疗方案的31例复发性卵巢癌及1例原发性腹膜癌患者进行回顾性分析。采用GCIG CA125反应评价标准或RECIST标准评估疗效;通过治疗方案的延后、减量及中断情况评估ABX方案的耐受性。结果32例卵巢癌及原发性腹膜癌患者中,铂类敏感者占15.6％（5／32）,铂类耐药／难治者占84.4％（27／32）。 ABX方案治疗前, CA125为（477.5±654.9）U／ml,CA125升高者26例（81.3％）。32例患者接受ABX为基础方案的总反应率为28.0％（9／32）,CA125完全缓解率为15.6％（5／32）。铂类敏感者的反应率为60.0％（3／5）,铂类耐药／难治者的反应率为22.2％（6／27）,两者差异无统计学意义（P＞0.05）。5例患者6个周期的化疗延后＞1周。治疗过程中未记录到剂量减少或治疗中断,亦未记录到ABX超敏反应的发生。结论 ABX为基础的方案在铂类敏感及铂类耐药／难治卵巢癌及原发性腹膜癌患者中均能产生临床疗效。在接受过多线化疗的卵巢癌及原发性腹膜癌患者中,ABX方案的总体耐受性较好。     

紫杉醇脂质体联合卡铂治疗晚期卵巢上皮癌的临床分析

目的研究紫杉醇脂质体联合卡铂方案化疗治疗晚期卵巢上皮癌的临床疗效和毒副作用。方法对经减瘤术后病理组织学确诊的Ⅲ一Ⅳ卵巢上皮癌患者26例,采用紫杉醇脂质体联合卡铂方案化疗,其中紫杉醇脂质体130～175mg／m^2第1天静脉滴注;卡铂300mg／m^2第2天静脉滴注,每21天为1个周期,每2个周期评价1次疗效。结果26例患者完全可以评价疗效,其中完全缓解7例,部分缓解11例,稳定6例,进展3例,总有效率为69．23％,其中Ⅲ期有效率为72．22％,Ⅳ期有效率为62．50％。中位疾病进展时间（MTYP）10个月（5～13个月）,无复发生存期5个月。毒副作用主要为骨髓抑制和胃肠道反应。结论紫杉醇脂质体联合卡铂方案治疗晚期卵巢上皮癌近期疗效好,毒副作用可以耐受,值得临床推广使用。     

External validation of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer

Background:

For various malignancies, prognostic models have shown to be superior to traditional staging systems in predicting overall survival. The purpose of this study was to validate and compare the performance of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer.

Methods:

A multi-institutional epithelial ovarian cancer database was used to identify patients and to evaluate the predictive performance of two nomograms, a prognostic index and FIGO (International Federation of Obstetrics and Gynecology) stage. All patients were treated for advanced-stage epithelial ovarian cancer between January 1996 and January 2009 in 11 hospitals in the eastern part of The Netherlands.

Results:

In total, 542 patients were found to be eligible. Overall performance did not differ between the three prognostic models and FIGO stage. The discriminative performance for Chi''s model was moderately good (c indices 0.65 and 0.68) and for the models of Gerestein and Teramukai reasonable (c indices between 0.60 and 0.62). The c indices of FIGO stage ranged between 0.54 and 0.62. After recalibration, the three models showed almost perfect calibration, whereas calibration of FIGO stage was reasonable.

Conclusion:

The three prediction models showed general applicability and a reasonably well-predictive performance, especially in comparison to FIGO stage. To date, there are no studies available that analyse the impact of these prognostic models on decision-making and patient outcome. Therefore, the usefulness of these models in daily clinical practice remains to be investigated.