|Year : 2018 | Volume
| Issue : 4 | Page : 433-438
A comparison between primary debulking surgery and primary chemotherapy in patients with advanced ovarian cancer: a retrospective study
Mohamed Esmat1, Mohamed Ashour2
1 Surgical Oncology Unit, Department of Surgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
2 Department of Clinical Oncology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
|Date of Submission||18-Jan-2019|
|Date of Acceptance||03-Mar-2019|
|Date of Web Publication||23-Apr-2019|
Surgical Oncology Unit, Department of Surgery, Faculty of Medicine, Al-Azhar University, Cairo, 12811
Source of Support: None, Conflict of Interest: None
Background Early detection of ovarian cancer is troublesome owing to the obscurity of conspicuous clinical symptoms. Hence, 75% of patients with ovarian cancer usually present and are diagnosed at an advanced stage (International Federation of Gynecology and Obstetrics stage IIIC or IV).
Objective This study was conducted to evaluate the surgical and oncological consequences of patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics III/IV) who were subjected to either primary debulking surgery (PDS) followed by chemotherapy or primary chemotherapy (PC) followed by interval debulking surgery (IDS).
Patients and methods We retrospectively reviewed the medical files of patients with advanced ovarian cancer who were admitted to the Surgical Oncology Unit, Bab-Elsharya University Hospital, between September 2008 and October 2013. Patients subjected to PDS succeeded by six cycles of chemotherapy, 6 weeks prior PDS, were enrolled in the PDS group, whereas patients subjected to three cycles of PC followed by IDS were enrolled in the PC-IDS group.
Results This study recruited 104 consecutive patients with advanced ovarian cancer who received either PDS (52 participants) or PC-IDS (52 participants). The median overall survival time was 29.3 and 30.1 months in PDS and PC-IDS groups, respectively. Moreover, no significant difference was observed between patients subordinated to PDS (18.2%) and PC-IDS (15.41%) regarding overall survival rates (log-rank test, P=0.273).
Conclusion PC-IDS can be an alternative procedure in the management of advanced ovarian cancer owing to not only similar survival rates but also with the advantages relative to PDS regarding postoperative morbidities.
Keywords: advanced ovarian cancer, chemotherapy, debulking
|How to cite this article:|
Esmat M, Ashour M. A comparison between primary debulking surgery and primary chemotherapy in patients with advanced ovarian cancer: a retrospective study. Al-Azhar Assiut Med J 2018;16:433-8
|How to cite this URL:|
Esmat M, Ashour M. A comparison between primary debulking surgery and primary chemotherapy in patients with advanced ovarian cancer: a retrospective study. Al-Azhar Assiut Med J [serial online] 2018 [cited 2019 Aug 20];16:433-8. Available from: http://www.azmj.eg.net/text.asp?2018/16/4/433/256762
| Introduction|| |
Ovarian cancer is the fifth commonest cancer among women and the deadest malignancy, in developed countries, among gynecological tumors, which affects an estimated 4400 patients annually in the UK ,. Early detection of ovarian cancer is troublesome owing to the obscurity of conspicuous clinical symptoms. Hence, 75% of patients with ovarian cancer usually present and are diagnosed at an advanced stage [International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV] .
Throughout the past era, primary debulking surgery (PDS) succeeded by chemotherapy was the standard treatment of advanced ovarian cancer . Debulking surgery has evolved since 1934 and constitutes significant increase in the survival rate, as survival rate depends mainly upon the size of the residual tumor after PDS ,. Presently, the tumor biology is more crucial than the surgical resection of the tumor, and the value of extensive cytoreduction surgery before PC is a doubtful issue in the literature .
Recent studies suggested primary chemotherapy (PC) followed by interval debulking surgery (IDS) as substitutional management for patients with advanced ovarian cancer, particularly in patients unsuitable for PDS . This procedure based on the significant response of patients to platinum-based chemotherapy leads to considerable symptomatic improvement, reduction of the tumor burden, enhancement of the adequate debulking rates, and minimization of the surgical invasiveness in the merits of less estimated blood loss, less complications, and refinement of the patients’ quality of life ,. Nevertheless, this treatment is usually associated with considerable disadvantages such as impediment of the actual state of the disease at the time of IDS, high rate of recurrence associated with significant chemoresistance, and reduction of the survival rates ,,.
The poor 5-year survival rate (25%)  of patients with advanced ovarian cancer brings to light the importance of the refinement of the treatment options. Thereafter, to shed light upon the contributions of debulking surgery and chemotherapy in patients with advanced pancreatic cancer, this retrospective study was conducted to evaluate the surgical and oncological consequences of patients with advanced ovarian cancer (FIGO III/IV) subjected to either PDS or PC-IDS.
| Patients and methods|| |
We retrospectively reviewed the medical files of patients with advanced ovarian cancer who were admitted at the Surgical Oncology Unit, Bab-Elsharya University Hospital between September 2008 and October 2013. We implemented this study in conformity with the Declaration of Helsinki and recommendations approved by the Ethics Unit, Faculty of Medicine, Al-Azhar University. We explained all the surgical and clinical procedures to all participants before their assignment of the informed consents.
Patients established clinically or by imaging to have a pelvic mass with extrapelvic extension that was proved to be a stage III or IV ovarian cancer based on FIGO classification and fit for surgery and chemotherapy were suitable for inclusion in the study. Consequently, advanced ovarian cancer was established pathologically by either biopsy or fine needle aspiration, which showed adenocarcinoma with presence of pelvic mass, metastasis outside the pelvis (>2 cm), regional lymph node metastasis, and the ratio of cancer antigen 125 (CA 125) to carcinoembryonic antigen (CEA) of more than 25; these parameters fulfilled the criteria for inclusion in the study. Patients with CA 125 : CEA ratio of less than or equal to 25 were subjected to further investigations to ensure the presence of primary tumor and to exclude the existence of gastrointestinal cancer. Eventually, patients with gastrointestinal tumors, a pelvic mass of benign nature, secondary ovarian cancer, unresectable tumor, and patients unsuitable for surgery were excluded.
To ensure the high levels of quality, the medical files of the included candidates were subjected to review by a surgical oncologist and a medical oncologist. All patients were subjected to history taking and laboratory investigations to reveal the following data: age, BMI, associated comorbidities, WHO performance status, liver functions tests, renal functions tests, blood profile, and serum tumor markers (CA 125 and CEA). Furthermore, all patients were subjected to histopathological examination, cytological examination, computed tomography, and MRI to retrieve the following information: tumor site, type, stage, and histological differentiation. Consequently, to exclude patients with gastrointestinal cancer, patients with CA 125 : CEA of less than or equal to 25 were subjected to mammography, gastroscopy, and colonoscopy. The regimen of chemotherapy and the operative and postoperative details were reviewed to explore the following data: surgical stage, operation time, the volume of residual disease, length of hospital stay, postmanagement morbidities, and overall survival (OS) rates.
Surgery and chemotherapy
Patients who were subjected to PDS succeeded by six cycles of chemotherapy, 6 weeks prior PDS, were enrolled in the PDS group, whereas patients subjected to three cycles of PC followed by IDS and succeeded by three cycles of chemotherapy were enrolled in the PC group. The regimen of chemotherapy included six cycles of carboplatin AUC5 or carboplatin AUC6 with additional paclitaxel 175 mg/m2 every 3 weeks. The disease burden was evaluated at the beginning and at the end of the cytoreduction, and patients with residual disease of more than 1 cm were subjected to further IDS, after three cycles of chemotherapy, after PDS. Throughout each chemotherapy cycle, strict clinical evaluation and laboratory appreciation of blood profile, renal functions, liver functions, and CA 125 levels were done.
Evaluation and follow-up
Throughout the study period, patients were subjected to regular clinical evaluation and laboratory assessment of CA 125 every month up to 10 months and then every 3 months till 2 years, and every 6 months for 6 years, and yearly until death. The progression of the disease was clarified based upon WHO criteria  and increase in the levels of CA 125 concentration according to Gynaecologic Cancer Inter Group criteria .
Nonparametric variables were expressed as median and range, and the difference between those groups was estimated using Mann–Whitney U-test. Moreover, categorical variables were elucidated as number and percentage and compared using χ2-test. Survival analysis was done using Kaplan–Meier methods to calculate OS rate and progression-free survival (PFS) rate. Cox-proportional hazards regression model for survival was used to assess the hazard ratios for specific variables, and the overall comparison was done using log-rank test. Analyses were performed using SPSS, v.23 software (IBM SPSS Statistics; IBM Corp., Armonk, New York, USA), and MedCalc software, version 14.8 (MedCalc Software, Mariakerke, Belgium). Two-sided P value was considered statistically significant at the value of less than 0.05.
| Results|| |
Patients demographics and surgical characteristics
This study included 104 consecutive patients with advanced ovarian cancer who received either PDS (52 participants) or PC-IDS (52 participants). The median age of the included candidates was 67 (39–87) and 68.5 (38–89) years in PDS and PC-IDS groups, respectively. Furthermore, 43 (82.6%) and 41 (78.8%) were of stage III in PDS and PC-IDS groups, respectively. There was a significant difference between the two groups regarding WHO performance stage 0 (P=0.041) and stage 1 (P=0.086), with significant high prevalence of mixed epithelial tumor among patients subjected to PDS (P=0.0391) ([Table 1]).
Regarding the operative variables, both groups showed a substantially significant difference (P=0.031) regarding surgical stage (IIIb), with a high prevalence among PDS group (17.3 vs. 3.84%) along with significantly shorter operation time in patients subjected to PDS (P=0.021). Patients subjected to PC-IDS showed a significantly higher rate of residual disease of 1–10 mm (P=0.01). Moreover, there was a significant higher incidence of postoperative complications in terms of hemorrhage (P=0.041), venous thromboembolism (P=0.025), infection (P=0.0096), and sepsis (P=0.002) among patients subjected to PDS ([Table 2]).
Overall survival and progression-free survival rates
The median OS time was 29.3 and 30.1 months in PDS and PC-IDS groups, respectively. Moreover, no significant difference was observed between patients subjected to PDS (18.2%) and PC-IDS (15.41%) regarding OS rates (log-rank test, P=0.273) ([Figure 1]). Moreover, PFS rates were similar between both groups (PDS=15.61 months and PC-IDS=16.32 months), with PFS of 3 and 3.2% in PDS and PC-IDS groups, respectively (log-rank test, P=0.306). Furthermore, in multivariate Cox regression model, patients aged more than 65 years experienced a high risk of death (1.8921 times) when compared with patients aged less than 65 years (P=0.0013), and patients with stage IV had a hazard ratio of 1.906 when compared with patients with stage III (P=0.0061). Furthermore, the presence of residual disease particularly more than 10 mm was a significant independent predictor not only for OS rate but also for PFS rate in patients with advanced ovarian cancer ([Table 3]).
|Figure 1 Kaplan–Meier curves showed the overall survival rate between patients subjected to primary debulking surgery (PDS) and patients subjected to primary chemotherapy and interval debulking surgery (PC-IDS).|
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|Table 3 Multivariate Cox regression analysis of patients undergoing primary debulking surgery or primary chemotherapy and interval debulking surgery for advanced ovarian cancer|
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| Discussion|| |
Advanced ovarian cancer is life-threatening condition that decreases the life of patients and hinders the quality of life, particularly owing to the obscurity of the optimal treatment that offers a conceivable survival rate and PFS rate . Hence, the high concern should be given to this area of research to enhance a new line of treatment and to improve the current evidence. The evidence evolved in our study brings to light that patients subjected to PDS or PC-IDS had a similar pattern of outcomes not only regarding the OS rate (18.2 vs. 15.41%) but also regarding PFS rate (3 vs. 3.2%). Moreover, patients aged more than 65 years, patients with stage IV, and those with residual disease particularly more than 10 mm had a higher risk of death throughout the study period. Despite the shorter median operation time for patients received PDS, they were associated with a considerable higher risk of postoperative complications.
In accordance with our results, Vergote et al.  illustrated that no difference was found between PDS and PC-IDS regarding OS rate or PFS rate, with a tendency of occurrence of more postoperative morbidities among patients subjected to PDS. Moreover, patients with large preoperative tumor size, those with large residual tumor, and old age patients had a higher risk of death throughout the study period . In contrast, a previous study showed a significant advancement of PDS when compared with PC . This discrepancy may be owing to a variety of demographic variables, apart from a considerable number of patients in our study aged more than 65 years, which was established to be an independent risk of death in patients with advanced ovarian cancer .
The complete resection rate occurred in PDS (36.5%) and PC-IDS (42.3%) groups was relatively low. This result reflects the early experience of our institute with cytoreduction at the time of the study and owing to the significant changes in the guidelines of chemotherapy in patients with advanced ovarian cancer.The presence of residual tumor was the most important independent predictor of survival in patients with advanced ovarian cancer. Herein, despite similar pattern of outcomes between PDS and PC-IDS groups, we recommend an optimal approach of cytoreduction with removal of all macroscopic residual tumor rather than the excision of lesions more than 1 cm in diameter followed by a regimen of chemotherapy rather than PC-IDS particularly with existence of fibrosis associated with PC, which may hinders the accessibility of IDS in the complete resection of macroscopic residual disease .
Despite the strength of our study, coexisting limitations evolved, such as the retrospective nature of the study which was associated with unavoidable selection bias; the small sample size, which restricts the subgroup survival analysis of different stages among patients; and the heterogeneity between both groups regarding some demographic and clinical parameters.
| Conclusion|| |
PC-IDS is an alternative and feasible procedure in the management of advanced ovarian cancer owing to not only similar OS and PFS rates but also having a potential advantage relative to PDS regarding postoperative morbidities. However, further randomized clinical trials with adequate sample size are needed to overcome the limitations of this study.
All authors participated in the following items: (i) conception and design of study, acquisition of data, and analysis and interpretation of data; (ii) drafting the article and revising it critically for important intellectual content; and (iii) providing final approval of the version to be published. The manuscript has been read and approved by all the authors.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Berrino F, de Angelis R, Sant M, Rosso S, Lasota MB, Coebergh JW et al.
Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995–1999: results of the EUROCARE-4 study. Lancet Oncol 2007; 8:773–783.
Coleman RL, Monk BJ, Sood AK, Herzog TJ. Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol 2013; 10:211.
Agarwal R, Kaye SB. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer 2003; 3:502.
Schwartz PE, Rutherford TJ, Chambers JT, Kohorn EI, Thiel RP. Neoadjuvant chemotherapy for advanced ovarian cancer: long-term survival. Gynecol Oncol 1999; 72:93–99.
Meigs JV, Greenough RB. Tumors of the female pelvic organs. Am J Med Sci 1935; 189:132.
Allen DG, Heintz AP, Touw FW. A meta-analysis of residual disease and survival in stage III and IV carcinoma of the ovary. Eur J Gynaecol Oncol 1995; 16:349–356.
Vergote I, Trope CG, Amant F, Kristensen GB, Ehlen T, Johnson N et al.
Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010; 363:943–953.
Bristow RE, Chi DS. Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis. Gynecol Oncol 2006; 103:1070–1076.
Everett EN, French AE, Stone RL, Pastore LM, Jazaeri AA, Andersen WA, Taylor PT Jr. et al.
.. Initial chemotherapy followed by surgical cytoreduction for the treatment of stage III/IV epithelial ovarian cancer. Am J Obstet Gynecol 2006; 195:568–574.
Inciura A, Simavicius A, Juozaityte E, Kurtinaitis J, Nadisauskiene R, Svedas E, Kajenas S. Comparison of adjuvant and neoadjuvant chemotherapy in the management of advanced ovarian cancer: a retrospective study of 574 patients. BMC Cancer 2006; 6:153.
Rauh-Hain J, Rodriguez N, Growdon W, Rodriguez N, Goodman A, Boruta D, Horowitz N et al.
Primary debulking surgery versus neoadjuvant chemotherapy in stage IV ovarian cancer. Ann Surg Oncol 2012; 19:959–965..
Rauh-Hain JA, Nitschmann CC, Worley MJ Jr, Bradford LS, Berkowitz RS, Schorge JO et al.
Platinum resistance after neoadjuvant chemotherapy compared to primary surgery in patients with advanced epithelial ovarian carcinoma. Gynecol Oncol 2013; 129:63–68.
Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 2002; 20:1248–1259.
WHO. WHO handbook for reporting results of cancer treatment. Geneva, Switzerland: WHO; 1979.
Vergote I, Rustin GJ, Eisenhauer EA, Kristensen GB, Pujade-Lauraine E, Parmar MK et al.
Re: new guidelines to evaluate the response to treatment in solid tumors [ovarian cancer]. J Natl Cancer Inst 2000; 92:1534–1535.
Aletti GD, Dowdy SC, Gostout BS, Jones MB, Stanhope CR, Wilson TO et al.
Aggressive surgical effort and improved survival in advanced-stage ovarian cancer. Obstet Gynecol 2006; 107:77–85.
Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N et al.
Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010; 363:943–953.
Vergote IB, De Wever I, Tjalma W, Van Gramberen M, Decloedt J, Van Dam P. Neoadjuvant chemotherapy versus primary debulking surgery in advanced ovarian cancer. Semin Oncol 2000; 3(Suppl 7):31–36.
Vergote I, Amant F, Kristensen G, Ehlen T, Reed NS, Casado A. Primary surgery or neoadjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer. Eur J Cancer 2011; 47:S88–S92.
[Table 1], [Table 2], [Table 3]