Perioperative morbidity and outcome of secondary cytoreduction for recurrent epithelial ovarian cancer

doi:10.1016/j.ejso.2010.04.012

European Journal of Surgical Oncology (EJSO)

Volume 36, Issue 6, June 2010, Pages 583-588

https://doi.org/10.1016/j.ejso.2010.04.012 Get rights and content

Abstract

Background

Despite radical surgical and chemotherapeutic treatment of ovarian cancer, the majority of patients develop recurrent disease. Secondary cytoreductive surgery can result in favourable outcome in selected patients, but information regarding feasibility, safety and perioperative outcome of these often complex procedures is limited.

Methods

Surgical parameters in patients with recurrent epithelial ovarian cancer selected for secondary cytoreduction were analysed and compared to patients undergoing primary cytoreduction.

Results

In total, 222 patients undergoing radical cytoreduction were analysed (48 patients for relapsed disease and 174 patients at primary diagnosis of advanced ovarian cancer). The range of surgical procedures was similar in both groups. In 48% of secondary cytoreductions ‘optimal surgical results’ (residual tumour <1 cm) were obtained and 33% of the patients had no residual disease compared to 82% and 58% at primary cytoreduction. There was no significant difference in perioperative complication rates. The duration of surgery was shorter and the number of transfused blood products was smaller at secondary cytoreduction (p < 0.001 and p = 0.001).

Conclusion

Secondary cytoreduction in relapsed ovarian cancer is safe and feasible and perioperative outcome is not inferior compared to primary cytoreduction. Surgery-associated morbidity should represent a minor aspect in the selection and counselling of patients regarding treatment options for recurrent ovarian cancer.

Introduction

Ovarian cancer accounts for the highest tumour-related mortality of all gynaecologic malignancies and is a common cancer in women.¹ There are an estimated number of 14 600 deaths due to this disease each year in the US.² Despite radical surgery and adjuvant systemic chemotherapy, the majority of patients develop recurrent disease and eventually die of their disease.³ Although primary cytoreductive surgery is well accepted as the crucial step of initial therapy and residual tumour after primary surgery is considered the most important prognostic factor, the use of cytoreductive surgery in the setting of recurrent disease is defined less clearly. Several retrospective studies suggest a benefit of secondary cytoreduction but until today, no data from randomized phase 3 trials is available.4, 5 Most retrospective analyses report improved survival in patients with complete secondary debulking (no residual tumour), while the role of so-called ‘optimal debulking’ (residual tumour <1 cm) for recurrent disease remains controversial.4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 Despite these results, surgical therapy still plays only a minor role in the treatment of recurrent ovarian cancer in clinical routine. Besides the lack of conclusive evidence this might also be caused by the technical complexity of secondary surgery in patients with repetitive abdominal procedures. Information regarding the feasibility and perioperative outcome of these surgical procedures is very limited. In most of the published retrospective studies, surgical procedures, perioperative morbidity and mortality were not reported systematically.¹¹

We conducted the current study to determine the surgical procedures and complications of secondary cytoreduction and evaluate the accomplishment of optimal surgical results in recurrent ovarian cancer compared to primary surgery.

Section snippets

Patients

All patients with advanced primary (stage III and IV) or relapsed epithelial ovarian cancer who presented for surgery at the University Medical Center Hamburg-Eppendorf between 1996 and 2004 were retrospectively analysed. Patients with ovarian carcinoma of low malignant potential (borderline tumours) and patients who underwent surgery solely for the correction of bowel obstruction were excluded from the analysis.

Altogether 222 patients were analysed in this study, including 48 patients with

Patients

A total of 222 patients were analysed in the study, including 48 patients with relapsed ovarian cancer and 174 with primary disease. Detailed patient characteristics are listed in Table 1. Median relapse-free survival for patients with recurrent disease before secondary cytoreduction was 18 months (range 5–100 months). There were nine patients with initial FIGO stage I–IIc included in the analysis of secondary debulking. Median time to recurrence (initial surgery until recurrence and secondary

Discussion

The availability of clinical data regarding resection rates and perioperative morbidity is an important cornerstone of decision making and patient counselling. There is some evidence that selected patients with relapsed ovarian cancer will benefit from surgical efforts when optimal surgical results are achieved.4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 However, the lack of criteria for patient selection and the technical complexity of these procedures cause reluctance to perform secondary

Conclusion

Our study suggests that secondary cytoreductive surgery for recurrent epithelial ovarian cancer can be accomplished with a similar complication rate, morbidity and mortality as primary debulking for advanced ovarian cancer. The rate of patients with complete cytoreduction however was significantly lower in patients with relapsed disease. Thus, counselling of patients regarding the selection for surgery in recurrent ovarian cancer remains difficult and prospective randomized trials are urgently

Conflict of interest statement

There is no conflict of interest involved with the presented data for any of the authors. The study was funded by internal departmental sources.

Acknowledgments

We would like to thank Drs. Christian Utler and Tina Osterholz as well as Prof. Christoph Thomssen for their help with the design of the study protocol.

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Cited by (30)

Secondary cytoreductive surgery - viable treatment option in the management of platinum-sensitive recurrent ovarian cancer
2018, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
The adequate selection of women with ROC for secondary cytoreductive surgery (SCS) is crucial due to the primary goal of SCS aiming at achieving optimal cytoreduction [5–7]. The prognostic importance of zero macroscopic residuum thus justifies extensive cytoreductive surgery, which may be associated with serious complications [8]. Primary objective of the present study was to evaluate the impact of the SCS on disease-free survival (DFS) and overall survival (OS) in women with ROC undergoing secondary cytoreduction following chemotherapy (SCS + CT) compared to patients receiving chemotherapy (CT) alone.
This study aimed to evaluate the impact of the secondary cytoreductive surgery on survival parameters in women with platinum-sensitive recurrent ovarian cancer who undergone secondary cytoreduction following chemotherapy compared to women who recieved chemotherapy alone.
In a retrospective study, data were rewieved from women who were diagnosed and treated with ovarian cancer and its primary platinum-sensitive recurrence at the University Hospital Brno in the Czech Republic between November 2009 and March 2016. Out of the total number of 62 patients with recurrence, 30 women underwent cytoreductive surgery plus chemotherapy and 32 were treated with chemotherapy alone. The good performance status expressed by ECOG score 0–1, the single site of recurrence regardless of platinum-free interval or multiple sites of recurrence but no carcinomatosis and platinum-free interval >12 months, and no or small-volume ascites (<500 ml) were considered inclusion criteria for cytoreductive surgery. Women not meeting these criteria were treated by chemotherapy alone. Descriptive statistics, Kaplan-Meier survival curves and Log-Rank test were used for statistical estimations.
The analysis confirmed more favorable prognosis in patient group treated with a combination secondary cytoreduction and chemotherapy. Mean disease-free survival (DFS) was 49.8 months (95% CI; 33.2–66.3) and mean overall survival (OS) stood at 54.0 months (95% CI; 39.4–68.6) in this patient cohort, while in patient group treated with chemotherapy alone it was found that mean DFS was 16.6 months (95% CI; 7.4–25.8) and mean OS stood at 26.2 months (95% CI; 16.6–35.8). When testing the difference between survival curves, statistically significant differences were observed in both DFS (p = 0.010) and OS (p = 0.007) rates between two treatment groups. Age < 60 years at the time of recurrence and zero macroscopic residual disease after secondary cytoreduction were identified as favorable prognostic factors for both DFS and OS in a multivariate analysis.
Secondary cytoreductive surgery is acceptable as a viable treatment option for highly selected women with ovarian cancer recurrence. Complete resection is considered ultimate goal of secondary cytoreduction on condition that the balance between maximal survival gain and minimal operative morbidity will be kept.
Neoadjuvant chemotherapy in ovarian cancer revisited
2016, Annals of Oncology
Despite the recent publication of two randomized controlled phase III trials addressing neoadjuvant chemotherapy in advanced ovarian cancer, the optimal timing of multimodal management in primary therapy is still under debate. As both studies met their primary end point by demonstrating non-inferiority, neoadjuvant chemotherapy followed by interval debulking surgery has been proposed to be an alternative standard for primary ovarian cancer treatment. Nevertheless, significant questions remain unanswered in both trials. Especially, the radicality of surgical therapy was below expectation with the median operating times of <3 h and complete gross resection in <20% of the patients. Consecutively, survival rates of patients undergoing primary debulking surgery were low. Since the primarily surgical question of ‘primary versus interval-surgery’ can only be answered if the key criteria ‘complete gross resection’ are present in a considerable percentage of patients, additional studies are needed and neoadjuvant chemotherapy should not be used to reduce surgical radicality for ovarian cancer treatment.
External validation of two prediction models of complete secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer
2015, Gynecologic Oncology
Citation Excerpt :
This suggests that there is room for improvement in the current diagnostic work-up of patients that will undergo SCS. Especially when taking into account that SCS has no curative intention and can even cause postoperative morbidity and subsequent loss of quality of life [4]. Recently, two prediction models have been developed to provide a quantitative estimate of complete SCS for an individual patient with recurrent epithelial ovarian cancer [5,6].
The purpose of this study was to validate the performance of two prediction models, the AGO score and the Tian model, of complete secondary cytoreductive surgery (SCS) in patients with recurrent epithelial ovarian cancer. The predictive value of both models for survival controlled for the outcome of SCS was analyzed and known predictive factors for complete SCS were tested.
A population-based database with 408 patients, who underwent SCS between 2000 and 2013 in 38 Dutch hospitals, was used. The validation cohorts for the AGO score and the model of Tian contained 273 (66.9%) and 257 (63.0%) patients, respectively.
The AGO score and Tian model showed a positive predictive value for complete SCS of 82.0% and 80.3% respectively, and a false negative rate of 68.5% and 55.6% respectively. A positive AGO score had no significant association with overall survival (HR 0.73; 95% CI 0.51–1.06) whereas the low risk score of the Tian model did (HR 0.62; 95% CI 0.41–0.93). A good performance status (OR 0.60; 95% CI 0.33–1.10) and the absence of ascites (OR 0.18; 95% CI 0.08–0.41) were prognostic factors for complete SCS.
Both the AGO score and the model of Tian showed a high positive predictive value for complete SCS but also relatively high false negative rates. However, before the two prediction models can be applied in daily clinical practice the usefulness of SCS itself has to be proven first by the three ongoing randomized controlled trials: DESKTOP III trial, the GOG 213 trial and the Dutch SOCceR trial.
The role of surgery in the management of patients with platinum-sensitive recurrent ovarian cancer: Survey among Dutch gynecologists and medical oncologists
2013, Gynecologic Oncology
Citation Excerpt :
Bristow et al. reported a mean peri-operative morbidity of 19.2% [5]. This percentage is comparable to the morbidity of primary cytoreductive surgery in ovarian cancer which was considered acceptable for most gynecologists (59.2%) and medical oncologists (63.3%) [17]. Several studies demonstrate that the specialization level of hospitals and the surgical volume of gynecologists positively influence outcomes of surgery and survival in primary ovarian cancer [18,19].
Evidence of randomized comparative clinical trials on surgery in recurrent platinum-sensitive ovarian cancer is non-existing. Three randomized phase 3 trials are ongoing. The aim of this study is to evaluate the current opinion of Dutch gynecologists and medical oncologists awaiting the results of these three trials.
A 16-item questionnaire was sent to all gynecologists (N = 124) and medical oncologists (N = 195) with special interest in gynecologic oncology in the Netherlands. The data were collected and analyzed using descriptive statistics.
In total, 80 (65.0%) gynecologists and 67 (34.0%) medical oncologists responded. Among the respondents, 11.3% and 26.9% were not convinced of the benefit of secondary cytoreductive surgery, respectively. For most gynecologists and medical oncologists completeness of primary surgery (74.6% and 75.5%, respectively) and performance status (100% and 98%, respectively) were important factors when considering surgery. For only about 17.5% of all respondents diagnostic laparoscopy before surgery is a prerequisite. Most respondents (81.7% and 87.8%, respectively) would use platinum-based chemotherapy with paclitaxel as their agents of choice after surgery. In general medical oncologists settle for a smaller gain in both progression free as well as overall survival than gynecologists.
Although most gynecologists and medical oncologists are already convinced of the usefulness of secondary cytoreductive surgery in certain patients, a better understanding of the real advantages and disadvantages and patient's selection criteria for secondary cytoreductive surgery will be achieved after the completion of three ongoing randomized controlled trials (DESKTOP III, GOG 213 and the SOCceR).
Hyperthermic intraperitoneal chemotherapy with carboplatin for optimally-cytoreduced, recurrent, platinum-sensitive ovarian carcinoma: A pilot study
2013, Gynecologic Oncology
Citation Excerpt :
There were no wound complications, peri-operative infections, or bleeding events. The median duration of stay was 5.5 (4–19) days which is similar to that reported by Schrag et al. for patients undergoing primary cytoreduction and notably less than the 23 days reported by Woelber et al. for secondary cytoreduction and the 14–18 days recently reported by Königsrainer et al. for patients undergoing secondary cytoreduction and HIPEC therapy [25–27]. The median time to the first post-HIPEC chemotherapy treatment was 31 (26–60) days, and the median number of chemotherapy treatments after HIPEC was 6 (5,6) with 1 patient declining further therapy after 5 treatments for personal reasons.
We aimed to evaluate the feasibility and tolerability of hyperthermic intraperitoneal carboplatin (HIPEC-carboplatin) following secondary cytoreduction for recurrent, platinum-sensitive ovarian cancer.
In a single institution prospective, pilot study, ten patients underwent secondary cytoreductive surgery followed by HIPEC-carboplatin at 1000 mg/m². Consolidation (6 cycles) was with platinum-based regimens. Adverse and quality of life were measured throughout treatment.
Twelve patients were enrolled of which 2 were excluded (one each for extra-abdominal disease indentified before surgery and suboptimal cytoreduction). All 10 remaining patients received prescribed HIPEC-carboplatin. There were no intra-operative complications or AEs attributable to HIPEC-therapy. Grade 1/2 nausea was the most common post-operative toxicity (6/10 patients). Two patients had grade 4 post-operative neutropenia and thrombocytopenia but only one experienced transient treatment delay. The median hospital stay was 5.5 days. 69/70 (98%) of planned chemotherapy doses were ultimately delivered with 1 patient electively forgoing her final treatment. At a median (range) follow-up of 16 (6–23) months, three patients have recurred at 8, 14, and 16 months from surgery. The median disease-free and overall survivals have not been reached. Fact-O scores were significantly lower following surgery (126 vs. 108, p < .01), but improved by completion of therapy (108 vs. 113, p = 0.27).
HIPEC-carboplatin at 1000 mg/m² following optimal cytoreduction for ovarian cancer is feasible. Surgical complications were not observed, and post-operative AEs were largely within expected ranges. Consolidation using standard platinum-based regimens was feasible following HIPEC-carboplatin, and preliminary survival data suggests efficacy. Further investigation of HIPEC-carboplatin in the setting of debulkable cancer recurrence is warranted.
Prognosis Following Surgery for Recurrent Ovarian Cancer and Diagnostic Criteria Predictive of Cytoreduction Success: A Systematic Review and Meta-Analysis
2023, Diagnostics

View all citing articles on Scopus

^c: Present address: Department of Gynaecology, Asklepios Klinik Nord – Heidberg, Hamburg, Germany.

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Perioperative morbidity and outcome of secondary cytoreduction for recurrent epithelial ovarian cancer

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Patients

Patients

Discussion

Conclusion

Conflict of interest statement

Acknowledgments

Eur J Obstet Gynecol Reprod Biol

Eur J Surg Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Crit Rev Oncol Hematol

Obstet Gynecol

Gynecol Oncol

Gynecol Oncol

Cancer facts and figures

Canc Stat

Cancer statistics

CA Cancer J Clin