When should Surgery be used for Recurrent Ovarian Carcinoma?

Cytoreductive surgery is an important column in the treatment of primary ovarian cancer. Surgical outcome is one of the most important prognostic factors and one of the few prognostic variables that can be influenced by therapists. Retrospective studies suggested that only complete cytoreduction was associated with a benefit. Therefore, definition of predictors of complete resection is of the utmost importance to avoid surgical burden in patients with both limited benefit of the procedure and limited overall life expectancy. Two prospective multicentre randomised surgical trials in platinum-sensitive recurrent ovarian cancer (DESKTOP III [NCT #01166737] and GOG 213 [NSC #704865]) comparing secondary cytoreductive surgery followed by platinum-based chemotherapy versus chemotherapy alone have been conducted. The results of the DESKTOP III were recently presented at the American Society of Clinical Oncology meeting in Chicago. It showed a benefit of secondary cytoreductive surgery exclusively in patients with complete resection with a progression-free survival of 5.6 months (P < 0.001). This overview aims to support this task and concentrates on the currently available data regarding surgery in recurrent ovarian cancer.     

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.     

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。     

Aggressive surgical strategies in advanced ovarian cancer: a monocentric study of 203 stage IIIC and IV patients

AIMS: The standard treatment for advanced ovarian cancer consists of cytoreductive surgery associated with a platinum/paclitaxel-based chemotherapy. Nevertheless, there is still the question as to the extent and timing of the surgical debulking. The aim of this study was to evaluate the place of surgery in the therapeutic sequence. PATIENTS AND METHODS: We reviewed data from all consecutive patients with stage IIIC and IV epithelial ovarian cancer, operated on at our institution between 1990 and 2005. Patients were divided into 2 groups, according to the position of surgery in the therapeutic sequence. Patients in group 1 received initial debulking surgery. Group 2 consisted of patients having received their first debulking after initial chemotherapy. RESULTS: Two hundred and three patients were identified and frequently underwent aggressive surgery, in particular, digestive surgery with bowel resections. Perioperative mortality and morbidity rates were low (2% and 14%, respectively) and there was no difference between the groups. Overall survival in group 1 for patients with complete cytoreduction (residual disease (RD)=0), optimal surgery (RD<1cm) or sub-optimal surgery (RD>1cm) was 50%, 30% and 14%, respectively. In group 2, overall survival following complete surgery was 30%, and no long-term survival was observed when surgery was not complete at the time of interval surgery. Survival was worse for patients who had received more than 4 cycles of neoadjuvant chemotherapy. CONCLUSION: This study confirms the importance of surgery in the prognosis of advanced ovarian cancer. Only the patient subgroup that underwent complete initial or interval surgery was associated with a prolonged remission. Optimal surgery with a controlled morbidity can be achieved in many cases, even if bowel resection is needed, at the time of primary debulking. In the interval cytoreductive surgery subgroup, the response to initial chemotherapy and surgery was found to be essential for prognosis.     

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。     

铂敏感复发性卵巢癌手术治疗的研究进展

复发性卵巢癌的高发率及致死率一直是临床上的难题。对部分铂类敏感的复发性卵巢癌患者,采用二次肿瘤细胞减灭术（SCS）及以铂类为基础的后续联合化疗可以延长生存时间,改善生活质量。因此,正确识别可以受益于手术治疗的患者是关键问题。目前已有研究提出一些预测模型来选择适合SCS的患者。本文就近年来对铂敏感复发性卵巢癌手术治疗的研究进展进行综述。     

Maximal cytoreductive effort in epithelial ovarian cancer surgery

The surgical management of advanced epithelial ovarian cancer involves cytoreduction, or removal of grossly-evident tumor. Residual disease after surgical cytoreduction of ovarian cancer has been shown to be strongly associated with survival. The goal of surgery is "optimal" surgical cytoreduction, which is generally defined as residual disease of 1 cm or less. However, the designation of "optimal" surgical cytoreduction has evolved to include maximal surgical effort and no gross residual disease. In order to achieve this, more aggressive surgical procedures such as rectosigmoidectomy, diaphragm peritonectomy, partial liver resection, and video-assisted thoracic surgery are reported and increasingly utilized in the surgical management of advanced ovarian cancer. The role of maximal surgical effort also extends to the recurrent setting where the goal of surgery should be complete cytoreduction. Patient selection is important in identifying appropriate candidates for surgical cytoreduction in the recurrent setting. The purpose of this article is to review the role of maximum surgical effort in primary and recurrent ovarian cancer.     

Maximal surgical effort increases the risk of postoperative complications in the treatment of advanced ovarian cancer

IntroductionSurgery is the cornerstone of the treatment for advanced ovarian cancer. Reaching complete cytoreduction resulting in no gross residual disease often requires complex surgery. The aim of this study was to assess the impact of increased surgical radicality on the risk of complications in the treatment of advanced ovarian cancer.Materials and methodsAll consecutive patients with advanced ovarian cancer (FIGO Stage IIIB-IVB) who had undergone primary or interval debulking surgery during a six-year study period were identified. In the midst of the study period, a surgical practice change towards maximal surgical effort occurred. Two groups were formed for the analysis: cohort A, that consisted of patients operated before the surgical paradigm shift and cohort B, that consisted of patients operated under the period of increased surgical radicality.Results252 patients were included in the analysis. Complete resection (R0) was achieved in 21.3% of surgeries in cohort A and in 51.2% in cohort B. The total postoperative complication rate was 76.2%. Most of the complications (86.5%) were minor (Clavien-Dindo I-IIIA). The patients in cohort B were at increased risk for complications, OR 2.94 (95%CI 1.58–5.47; p = 0.001). As for the approach to cytoreduction (primary vs. interval debulking), there was no statistically significant association with the occurrence of postoperative complications (p = 0.659).ConclusionIn the present study more extensive surgeries led to better surgical results but increased postoperative morbidity. Postoperative complication rates were similar in both primary and interval debulking surgeries.     

Cytoreductive surgery and intraoperative hyperthermic chemoperfusion for advanced ovarian carcinoma

BACKGROUND: Optimal cytoreductive surgery combined with intraoperative hyperthermic chemoperfusion (IHCP) is a therapy that potentially could improve survival in a select group of patients with advanced ovarian cancer. The purpose of this study was to review the results of cytoreductive surgery and IHCP for advanced ovarian cancer and to identify factors that may predict which patients maximally benefit from this aggressive treatment. METHODS: Patients treated with cytoreduction followed by IHCP for ovarian cancer were identified from an IHCP database from 1/2001 through 3/2004. Several factors including resection status, peritoneal cancer index (PCI), and prior surgery were evaluated for their ability to predict survival in our cohort of patients. RESULTS: Thirteen patients with ovarian cancer treated with cytoreductive surgery followed by IHCP were identified. The 3-year overall survival rate for all thirteen patients was 55%. The median disease-free survival was 15.4 months (3-year disease-free survival, 11%). Several factors including PCI score (<6), ability to resect all gross disease, and previous surgical exploration appeared to impart an overall survival advantage. CONCLUSIONS: The use of IHCP coupled with optimal cytoreduction is a safe and effective treatment for advanced ovarian carcinoma. However, the proper selection of patients who will benefit most from the therapy is essential for the success of the treatment.     

Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials

BACKGROUND:

Primary surgery followed by platinum‐taxane based chemotherapy has been the standard therapy in advanced ovarian cancer. However, the prognostic role of complete and so‐called optimal and suboptimal debulking and its interaction with biological factors has not been not fully defined.

METHODS:

Exploratory analysis was conducted of 3 prospective randomized trials (AGO‐OVAR 3, 5, and 7) investigating platinum‐taxane based chemotherapy regimens in advanced ovarian cancer conducted between 1995 and 2002.

RESULTS:

A total of 3126 patients were analyzed. Approximately one‐third each fulfilled criteria for complete resection (group A), small residual tumor burden of 1‐10 mm (group B), or macroscopic residual disease exceeding 1 cm in diameter (group C). Multivariate analysis showed improved progression‐free and overall survival for group A with complete resection compared with groups B or C (P < .0001). The impact of so‐called optimal debulking as in group B showed a smaller prognostic impact compared with group C. Further independent prognostic factors for overall survival were age, performance status, grade, FIGO stage, and histology, namely the mucinous subtype. An interaction between residual tumor and some biologic factors was demonstrated.

CONCLUSIONS:

The goal of primary surgery should be complete resection. The prognostic impact of tumor biology seemed to be partially overruled by residual tumor and further evaluation of biologic factors should stratify for residual tumor. Cancer 2009. © 2009 American Cancer Society.     

Surgical cytoreduction in recurrent ovarian carcinoma in patients with complete response to paclitaxel-platinum.

AIM: The objective was to analyse the impact of secondary cytoreductive surgery in patients with recurrent ovarian carcinoma. METHODS: Retrospective review of 572 consecutive patients with primary ovarian carcinoma. Thirty-eight patients with intraabdominal/pelvic recurrence consisted the study group. Clinical variables affecting tumour resectability and survival were evaluated. RESULTS: Complete tumour resection was obtained in 42% of patients. A solitary tumour recurrence was independently associated with complete tumour resection (p=0.009). Median survival for patients with complete and incomplete tumour resection was 51.8 and 19.9 months. The parameter, residual tumour, was found independently correlated with survival after the relapse surgical procedure (p=0.02). However, including also the parameter, number of relapse tumour sites, in the multivariate analysis, the parameter, residual tumour, was no longer significantly associated with survival. CONCLUSIONS: Complete tumour resection following secondary cytoreductive surgery is associated with improved survival in selected groups of patients with recurrent ovarian cancer. However, other clinical factors than surgical cytoreduction are of considerable significance in determining the outcome of the salvage treatment.     

The role of surgery in ovarian cancer with special emphasis on cytoreductive surgery for recurrence

PURPOSE OF REVIEW: The role of cytoreductive surgery for recurrent ovarian cancer has not clearly been defined, and randomized trials are lacking. Some series have reported favorable outcomes for selected patients. This review summarizes the available evidence for selecting patients and the results of cytoreductive surgery in recurrent ovarian cancer. RECENT FINDINGS: A Medline search identified 23 series including 1795 patients (21-285 patients per study). Patients who underwent cytoreductive surgery for recurrence were highly selected. Complete tumor resection was feasible in 9 to 82% of patients and was commonly associated with prolonged survival. A variety of predictive and prognostic factors for complete resection were reported. Good performance status, disease characteristics (e.g. peritoneal carcinosis), and outcome of prior surgery seemed to have an impact on surgical outcome. By contrast, disease-free survival played only a minor role, especially in patients with recurrence later than 6 months after primary treatment. SUMMARY: Prospective evaluation of predictive scores for successful cytoreductive surgery in recurrent ovarian cancer is urgently needed. In a second step, randomized trials evaluating the role of surgery in the treatment strategy of recurrent ovarian cancer should be initiated. Until then, experienced and trained surgeons might offer surgery for recurrent disease to individually selected patients after giving information about the potential benefit and about the limited available evidence regarding this strategy.     

Comprehensive approach to advanced primary and recurrent ovarian cancer: a personal experience

Despite improvements in chemotherapy agents and schedules and new drug combinations, epithelial ovarian cancer remains a leading cause of gynecologic cancer death in Western countries. It is usually diagnosed at late stages of the disease, which makes complete surgical resection technically more difficult. The targeted comprehensive approach described in this review includes cytoreductive surgery and perioperative intraperitoneal chemotherapy. The goal of this aggressive therapy is to remove all the macroscopic disease with the use of peritonectomy procedures and visceral resections, and also to eradicate microscopic disease using heated intraoperative intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. Patients that received a complete cytoreduction followed by perioperative intraperitoneal chemotherapy had an improved survival, with reasonable morbidity and mortality, as compared with those who received incomplete cytoreduction.     

Locoregional recurrence of ovarian cancer: the place of surgery

Standard therapy for advanced ovarian cancer includes cytoreductive surgery associated with platin based chemotherapy. Secondary surgery for recurrent ovarian cancer remains controversial. Actually there is not randomized trial based on this question. Furthermore literature shows that patients with recurrent disease may derive a significant survival benefit from optimal debulking. The datas availables indicate that prolonged disease free interval and feasibility of complete surgical resection are the main prognosis criteria. Proper selection of patients with recurrent ovarian cancer is essential to improve the therapeutic benefit of secondary surgery. There is a large place for trials and evaluation of innovatives techniques as hyperthermic intraperitoneal chemotherapy or intraperitoneal radio-immunotherapy.     

The surgical management of women with ovarian cancer in the south west of England.

The surgical management of epithelial ovarian cancer in the South West of England was studied in the two years 1997-1998 in order to determine the factors that influence the outcome of surgery and to provide a baseline from which to assess the effect of centralisation of cancer services. All hospitals in the South West region of England participating in the Regional Cancer Organisation's longitudinal study of outcomes in gynaecological malignancies are included. Six hundred and eighty-two patients with epithelial ovarian cancer were registered with the RCO in the two-year study period. Five hundred and ninety-five women were offered primary cytoreductive surgery of which 438 were said to be optimally cytoreduced. Applying multivariate models to analyse the outcome of surgery, older patients (OR = 0.82 per 5-year increase in age, P = 0.0003), patients treated in hospitals managing fewer than ten cases of ovarian cancer per year (OR = 1.92, P = 0.02) and patients with FIGO stage 3 (OR = 0.02, P < 0.0001) or 4 (OR = 0.002, P < 0.0001) disease were less likely to be optimally cytoreduced. Gynaecological oncologists were 2.06 times more likely to attain optimal cytoreduction when compared to general gynaecologists and this was statistically significant (P = 0.01). The results from this study support the argument that limiting surgery for ovarian malignancy to specialised surgeons improves the extent of cytoreductive surgery.     

Systematic lymphadenectomy in ovarian cancer at second-look surgery: a randomised clinical trial

Background:The role of systematic aortic and pelvic lymphadenectomy (SAPL) at second-look surgery in early stage or optimally debulked advanced ovarian cancer is unclear and never addressed by randomised studies.Methods:From January 1991 through May 2001, 308 patients with the International Federation of Gynaecology and Obstetrics stage IA-IV epithelial ovarian carcinoma were randomly assigned to undergo SAPL (n=158) or resection of bulky nodes only (n=150). Primary end point was overall survival (OS).Results:The median operating time, blood loss, percentage of patients requiring blood transfusions and hospital stay were higher in the SAPL than in the control arm (P<0.001). The median number of resected nodes and the percentage of women with nodal metastases were higher in the SAPL arm as well (44% vs 8%, P<0.001 and 24.2% vs 13.3%, P:0.02). After a median follow-up of 111 months, 171 events (i.e., recurrences or deaths) were observed, and 124 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for progression and death were not statistically different (hazard ratio (HR) for progression=1.18, 95% confidence interval (CI)=0.87-1.59; P=0.29; 5-year progression-free survival (PFS)=40.9% and 53.8%; HR for death=1.04, 95% CI=0.733-1.49; P=0.81; 5-year OS=63.5% and 67.4%, in the SAPL and in the control arm, respectively).Conclusion:SAPL in second-look surgery for advanced ovarian cancer did not improve PFS and OS.     

Splenectomy and surgical cytoreduction in epithelial ovarian cancer: a review

HANPRASERTPONG J. & FUJIWARA K. (2011) European Journal of Cancer Care 20 , 287–293
Splenectomy and surgical cytoreduction in epithelial ovarian cancer: a review Surgical cytoreduction and platinum/taxane combination chemotherapy are the mainstay for the treatment of epithelial ovarian cancer patients. In order to minimise the tumour mass before chemotherapy, cytoreductive surgery is usually performed first. Currently, a splenectomy is included as part of surgical cytoreduction in epithelial ovarian cancer, but it is rarely performed. A splenectomy is also performed as part of secondary cytoreduction surgery. Although there are many reports on surgical techniques, safety and associated clinical outcomes of a splenectomy as a standard adjunct of ovarian cytoreductive surgery, most evidence is from case(s) reports, with only a few studies. Thus, we conducted a review of the literature on this unusual procedure in the context of primary and secondary cytoreduction of epithelial ovarian cancer to assess the published evidence for its efficacy and safety.     

复发性卵巢癌治疗时机和策略的探讨

背景与目的:复发性卵巢癌的预后不良,对其处理仍未规范。本研究目的是探讨复发性卵巢癌治疗的意义和方法。方法:随机收集我院1990年2月至2000年12月收治的复发性卵巢癌54例。详细记录与肿瘤复发及治疗相关的临床数据,观察病例总的生存时间。对与生存有关的因素进行多因素分析,计算95％可信区间(95％ CI)。结果:多因素分析表明,肿瘤的无化疗缓解期>6个月,采用手术加化疗的治疗方法,可以明显延长患者的生存期(P<0.05)。与肿瘤的无化疗缓解期<6个月者相比,>6个月者的OR值为0.389。与采用手术加化疗方法比较,单一化疗的OR值为4.194。增加化疗的疗程数可能适当延长生存期(P=0.07)。与疗程数<6者比较,>10疗程的OR值为0.346。治疗开始的时间和化疗方案的选择对于生存期无明显影响(P<0.05)。结论:肿瘤的无化疗缓解期是复发性卵巢癌治疗的前提条件。对于肿瘤无化疗缓解期>6个月的病例,建议采取手术加化疗的治疗策略,以延长生存时间。对于铂类耐药者,治疗方法的选择以改善生活质量为目的。     

Total Colectomy as a Part of Ultra-Radical Surgery for Ovarian Cancer—Short- and Long-Term Outcomes

(1) Background: The aim of this study was to assess the outcomes for patients who underwent total colectomy (TC) as a part of surgery for ovarian cancer (OC). (2) Methods: We performed a retrospective analysis of 1636 OC patients. Residual disease (RD) was reported using Sugarbaker’s completeness of cytoreduction score. (3) Results: Forty-two patients underwent TC during primary debulking surgery (PDS), and four and ten patients underwent TC during the interval debulking surgery (IDS) and secondary cytoreduction, respectively. The median overall survival (mOS) in OC patients following the PDS was 45.1 months in those with CC-0 (21%) resection, 11.1 months in those with CC-1 (45%) resection and 20.0 months in those with CC-2 (33%) resection (p = 0.28). Severe adverse events were reported in 18 patients (43%). In the IDS group, two patients survived more than 2 years after IDS and one patient died after 28.6 months. In the recurrent OC group, the mOS was 6.9 months. Patient age above 65 years was associated with a shortened overall survival (OS) and the presence of adverse events. (4) Conclusions: TC as a part of ultra-radical surgery for advanced OC results in high rates of optimal debulking. However, survival benefits were observed only in patients with no macroscopic disease.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial and recurrent ovarian carcinoma: a single center experience

Background: With standard treatment of epithelial ovarian cancer (EOC), prognosis is very poor. The aim of this study is to show early and late results in patients who underwent cytoreductive surgery and intraperitoneal chemotherapy.

Patients and methods: This was a retrospective single centre study. All patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) or modified early postoperative intraperitoneal chemotherapy (EPIC) were included in the study.

Results: In the period 1995–2014, 116 patients were treated, 55 with primary EOC and 61 with recurrent EOC. The mean age was 59 years (26–74). Statistically, median survival time was significantly longer in the group with primary advanced cancer of the ovary (41.3 months) compared to relapsed ovarian cancer (27.3 months). Survival for the primary EOC was 65 and 24% at 3 and 5 years, respectively. Survival for recurrent EOC was 33 and 16% at 3 and 5 years, respectively. Mortality was 1/116 (0.8%). Morbidity was 11/116 (9.5%). Peritoneal cancer index (PCI) was ≤20 in 59 (51%) patients and statistically, their average survival was significantly longer than in the group of 57 (49%) patients with PCI?>20 (p?=?0.014).

Conclusions: In advanced or recurrent EOC, a curative therapeutic approach was pursued that combined optimal cytoreductive surgery and intraperitoneal chemotherapy. PCI and timing of the intervention (primary or recurrent) were the strongest independent prognostic factors.