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

doi:10.1016/j.ejso.2008.01.005

European Journal of Surgical Oncology (EJSO)

Volume 35, Issue 2, February 2009, Pages 135-143

https://doi.org/10.1016/j.ejso.2008.01.005 Get rights and content

Abstract

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 < 1 cm) or sub-optimal surgery (RD > 1 cm) 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.

Introduction

The standard treatment for advanced ovarian cancer consists of cytoreductive surgery associated with a platinum/paclitaxel-based chemotherapy.1, 2 Several studies have demonstrated that the result of the surgery, defined by the amount of residual disease (RD), was the most important factor impacting on survival.3, 4, 5, 6, 7, 8, 9 However, these results have not been tested by randomized studies, comparing maximal surgery with a minor radical surgical approach or chemotherapy alone. Progress in chemotherapy regimens and advances in surgical techniques have developed concurrently, making it impossible to determine their respective impact on the improvement of the prognosis. Therefore, there are still questions as to the role of surgery in the therapeutic sequence. For some authors, the increase in survival associated with optimal debulking is limited to patients with a less advanced disease, and the results of the surgical studies could be related to the biology of the cancer.10, 11 For others, initial aggressive surgery is associated with an important morbidity delaying chemotherapy or results in a poor quality of life.¹² Additionally, some studies were recently published concerning the results of interval surgery¹³ and the adoption of neoadjuvant chemotherapy (NAC) in the management of advanced ovarian cancer.14, 15, 16, 17, 18 Consequently, the prescription of NAC has increased over the last years; the first debulking is now often attempted only after 3–6 cycles of chemotherapy.

The purpose of the present study was to evaluate the position of cytoreductive surgery in the therapeutic sequence in a series of ovarian cancers treated in our institution. We tried to answer to the following questions: which patients could benefit from initial surgery, at what cost and for what oncological results? What are the indications and the results of interval surgery after NAC?

Section snippets

Patients

All the patients diagnosed with primary ovarian cancer operated on at our institute between 1990 and 2005 were recorded. Patients with stage IIIC or IV, undergoing primary or interval surgery for epithelial ovarian cancer, were consecutively included in this study.

Surgery

Surgical staging and grading were defined according to the FIGO criteria. The initial extent of the disease at the start of each intervention was quantified using the peritoneal cancer index, derived from Sugarbaker's publication.¹⁹

Patients

During the indicated period, 203 patients at stage IIIC (160) or IV (43), underwent primary or interval surgery at our institution and were eligible for inclusion. The average age at diagnosis was 60 years (range: 28–88), and the average follow-up duration was 70 months. Most of them presented an extended disease (Table 1). Considering all patients with FIGO stage IIIC and IV disease, the median survival was 35 months (overall survival at 5 years: 27%).

Surgery

One hundred and four patients had their

Cytoreductive surgery

The concept of cytoreductive surgery in advanced ovarian cancer is based on several theoretical and clinical aspects.3, 20 The removal of large masses of tumor has been reported to improve the patients' general status and to enhance the efficacy of chemotherapy.²¹ According to Griffiths,²⁰ several studies have demonstrated that successful cytoreduction to a small-volume disease increases the frequency of complete response and survival.22, 23, 24, 25, 26, 27 In a meta-analysis of 6885 patients

Conclusion

The survival of patients with advanced ovarian cancer is mainly influenced by 3 factors: the extent of the disease at the time of diagnosis, the biology of the tumor and its chemosensitivity and, lastly, the size of the RD after surgery. Today, this latter factor is the only 1 modifiable by therapeutic approach. The removal of all macroscopic tumors as soon as possible in the therapeutic sequence seems to be primordial for improving chemotherapy efficacy and survival. For patients with advanced

Conflict of interest

The authors declare that they have no proprietary, financial or other personal interest of any nature.

Acknowledgements

The authors thank Dr Sharon Lynn Salhi and Brian Hawkins for presubmission editorial assistance.

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Intrathoracic surgery as part of primary cytoreduction for advanced ovarian cancer: Going to the next level – A Memorial Sloan Kettering Cancer Center study
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We investigated the feasibility, safety, and survival outcomes of intrathoracic cytoreduction during primary debulking surgery (PDS) for advanced ovarian cancer.
We conducted a database review of patients with stage IIIB-IV ovarian (including fallopian tube and primary peritoneal) carcinoma who underwent PDS at our institution from 01/01/2006–9/30/2021. Patients who underwent intrathoracic cytoreduction as part of primary treatment were included. Patients who received neoadjuvant chemotherapy or surgery for reasons other than cytoreduction were excluded.
Among 178 patients identified for inclusion, complete gross resection (CGR) in the abdomen and thorax was achieved in 131 (74%); 45 (25%) had optimal cytoreduction, and 2 (1%) had suboptimal cytoreduction. Thirty-one patients (17%) had at least one grade ≥ 3 complication; 8 were possibly related to intrathoracic cytoreduction. There were no deaths within 30 days following surgery. Median length of follow-up among survivors was 53.4 months. Among all patients, the median PFS was 33.6 months (95% CI: 24.7–61.9) and the 3-year PFS rate was 48.9% (95% CI: 41.2%–56.2%). Median OS was 81.3 months (95% CI: 68.9–103). When stratified by residual disease status, median PFS was 51.8 months when CGR was achieved versus 16.7 months with residual disease (HR: 2.17; P < .001) and median OS was 97.6 months when CGR was achieved versus 65.9 months with residual disease (HR: 2.05; P = .003).
Intrathoracic cytoreduction during PDS for advanced ovarian cancer is both safe and feasible. CGR can be achieved in patients with intrathoracic disease if properly selected, and could significantly improve both PFS and OS.
Ten-year conditional probability of survival for patients with ovarian cancer: A new metric tailored to Long-term survivors
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We assessed a conditional probability of survival (CPS) model to determine the probability of living 10 years after ovarian cancer diagnosis after having already survived 5 years.
We identified patients newly diagnosed with high-grade epithelial ovarian cancer from 1/1/2001–12/31/2009 and treated at our institution. Patients with <3 years follow-up were excluded. CPS was defined as the probability of surviving additional years (y) based on the condition a patient had already survived a given time (x): S(x + y)/S(x). Confidence intervals were estimated using a variation of Greenwood's formula.
Of 916 patients meeting inclusion criteria, 473 (52%) were diagnosed from 2001 to 2005 and 443 (48%) from 2006 to 2009. Median age at diagnosis was 60 years (range, 25–95). The conventional 10-year OS rate for all patients was 29% (95% CI: 26%–32%)—75% (95% CI: 68%–82%) for stage I/II disease, 22% (95% CI: 19%–26%) for stage III, and 6.9% (95% CI: 3.9%–12%) for stage IV. For patients <65 years, the 10-year CPS for 5-year survivors was 65% (95% CI: 59%–70%); for those ≥65 years, it was 48% (95% CI: 38%–57%). For patients <65 years, the 10-year CPS for 5-year survivors by stage was: stage I/II, 89% (95% CI: 81%–94%); stage III, 58% (95% CI: 50%–66%); and stage IV, 26% (95% CI: 12%–42%). For patients ≥65 years, rates by stage were 78% (95% CI: 53%–91%), 42% (95% CI: 30%–53%), and 29% (95% CI: 7%–56%), respectively.
For long-term survivors with high-grade epithelial ovarian cancer, CPS provides better prediction of survival than conventional methods.
The BUMPy road of peritoneal metastases in ovarian cancer
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Ovarian cancer is the most common cause of death due to gynecologic malignancies, with more than 70% of patients presenting with advanced stage disease at the time of diagnosis. The extent and distribution of tumor guide primary treatment selection and clinical management. While primary cytoreductive surgery with complete tumor resection improves survival, patients with extensive peritoneal disease may benefit from neoadjuvant chemotherapy first to reduce tumor burden followed by interval cytoreductive surgery. Imaging plays an essential role in triaging patients including selecting patients who may benefit from neoadjuvant chemotherapy before cytoreductive surgery. Interestingly, there are no universally established criteria to predict resectability and local practices depend on local guidelines and surgeon preferences. Nevertheless, certain anatomical tumor locations are known to be difficult to resect and are associated with suboptimal cytoreduction or require special surgical considerations. This review discusses the recent advances in the initial management of patients with ovarian cancer, a practical approach to the assessment and communication of peritoneal metastases locations on CT and MRI. It also explores recent advances in genomics profiling and radiomics that may influence the initial management of these patients.
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To evaluate and compare overall survival and progression-free survival in two groups of patients with advanced ovarian cancer, managed by neoadjuvant chemotherapy (3 cycles or more) followed by interval debulking surgery. Secondary objectives regarded surgical morbidity and extent of cytoreduction.
We conducted a retrospective study, in a referral center, evaluating the management of patients diagnosed with advanced ovarian cancer (FIGO IIIC-IV) beneficiating of interval surgery after neoadjuvant chemotherapy. We compared two groups, one in which patients underwent 3 cycles of chemotherapy before surgery, and a second group in which patients underwent more than 3 cycles.
140 patients underwent interval surgery after neoadjuvant chemotherapy. Among these patients, 45 patients underwent 3 or less cycles (group 1) and 95 patients more than 3 cycles (group 2). There was no statistical difference for overall and progression free survival. The mean overall survival was 58,4 months for group 1 and 58,3 for group 2 (p.value = 0.56). The mean progression free survival was 30,5 months for group 1 and 23,8 months for group 2 (p.value = 0.17). More posterior pelvectomies were realized in group 1 compared to group 2 with a statistically significant difference (p=0,01). There was no difference regarding complete macroscopic difference during the surgery between the 2 groups (p=0,09).
Debulking surgery is an invasive and heavy procedure and is not always possible in first line. Neoadjuvant chemotherapy followed by interval debulking surgery is an accepted alternative. The number of administered cycles is questionable, and does not seem to have a significant impact on overall survival and progression free survival. However, surgical morbidity is significantly reduced by increased cycles of chemotherapy.
A radical approach to achieve complete cytoreductive surgery improve survival of patients with advanced ovarian cancer
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Cytoreductive surgery of locally advanced ovarian cancer has evolved in the last few years from surgery to remove macroscopic residual disease (< 1 cm; R2b) to macroscopic complete cytoreductive surgery with no gross residual disease (R1). The aim of this study was to evaluate the impact of the adoption of a maximalist surgical approach on postoperative complications, disease recurrence and survival.
This was a retrospective study using prospectively collected data on patients who received either conservative approach (CA) or radical approach (RA) surgical treatment for primary ovarian cancer stage IIIc/IVa/IVb between June 2006 and June 2013.
Data for 114 patients were included, 33 patients in the CA group and 68 patients in the RA group were consequently analysed. In the RA group, operative time was longer, in relation to more complex surgical procedures; with more blood losses and a higher rate of compete macroscopic resection. Totally, 77% of the patients had postoperative complications, with more grade I/II complications in the RA group but the same rates of grade III/IV complications in the both groups (P = 0.14). For all patient study population, the overall and disease-free survivals were improved in case of no macroscopic residual disease. Overall survival was improved in the RA group (P = 0.05), with no difference in terms of disease-free survival (P = 0.29)
A radical approach in advanced ovarian cancer allows a higher rate of complete cytoreductive surgery impacting overall survival. However, a non-significant trend for increased mild complications (grade I/II) rate is observed in this group.
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Citation Excerpt :
Increased adoption of NACT has generated research interest into the appropriate surgical goals at the time of IDS. Current data support that every effort should be made to resect all visible disease to achieve CSR, as this confers the best survival benefit in patients undergoing NACT-IDS.2–5,8–14,17,18 In this study, the longest PFS and OS were seen among patients with CSR, as well as ≤1 cm-SL.
Complete surgical resection affords the best prognosis at the time of interval debulking surgery. When complete surgical resection is unachievable, optimal residual disease is considered the next best alternative. Despite contradicting evidence on the survival benefit of interval debulking surgery if macroscopic residual disease remains, the current definition of “optimal” in patients undergoing interval debulking surgery is defined as largest diameter of disease measuring ≤1.0 cm, independent of the total volume of disease.
To examine the relationship between volume and anatomic distribution of residual disease and oncologic outcomes among patients with advanced-stage epithelial ovarian/fallopian tube/primary peritoneal carcinoma undergoing neoadjuvant chemotherapy then interval debulking surgery. For patients who did not undergo a complete surgical resection, a surrogate for volume of residual disease was used to assess oncologic outcomes.
Patient demographics, operative characteristics, anatomic site of residual disease, and outcome data were collected from medical records of patients with International Federation of Gynecology and Obstetrics stage IIIC and IV epithelial ovarian cancer undergoing interval debulking surgery from January 2010 to July 2015. Among patients who did not undergo complete surgical resection but had ≤1 cm of residual disease, the number of anatomic sites (single location vs multiple locations) with residual disease was used as a surrogate for volume of residual disease. The effect of residual disease volume on progression-free survival and overall survival was evaluated.
Of 270 patients undergoing interval debulking surgery, 173 (64.1%) had complete surgical resection, 34 (12.6%) had ≤1 cm of residual disease in a single anatomic location, 47 (17.4%) had ≤1 cm of residual disease in multiple anatomic locations, and 16 (5.9%) were suboptimally debulked. Median progression-free survival for each group was 14, 12, 10, and 6 months, respectively (P<.001). Median overall survival for each group was: 58, 37, 26, and 33 months, respectively (P<.001).
Following interval debulking surgery, patients with complete surgical resection have the best prognosis, followed by patients with ≤1 cm single-anatomic location disease. In contrast, despite being considered “optimally debulked,” patients with ≤1 cm multiple-anatomic location disease have a survival similar to suboptimally debulked patients.

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

Abstract

Aims

Patients and methods

Results

Conclusion

Introduction

Section snippets

Patients

Surgery

Patients

Surgery

Cytoreductive surgery

Conclusion

Conflict of interest

Acknowledgements

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