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 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Discussion
 » Conclusion
 » Acknowledgment
 »  References
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ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 2  |  Page : 284-287
 

An audit of cytoreductive surgeries in ovarian cancer from a rural based cancer center


1 Department of Surgical Oncology, Malabar Cancer Centre, Thalassery, Kerala, India
2 Department of Clinical Hematology and Medical Oncology, Malabar Cancer Centre, Thalassery, Kerala, India
3 Department of Radiation Oncology, Malabar Cancer Centre, Thalassery, Kerala, India
4 Department of Imageology, Malabar Cancer Centre, Thalassery, Kerala, India
5 Department of Cancer Registry, Division of Clinical Research and Biostatistics, Malabar Cancer Centre, Thalassery, Kerala, India
6 Department of Clinical Laboratory Services and Translational Research, Division of Oncopathology, Malabar Cancer Centre, Thalassery, Kerala, India

Date of Web Publication6-Jan-2017

Correspondence Address:
S B Dessai
Department of Surgical Oncology, Malabar Cancer Centre, Thalassery, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.197743

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 » Abstract 

Background and Objective: Ovarian cancers are frequently seen at an advanced stage in our center. This audit was planned to see the morbidity and efficacy of different types of cytoreductive surgeries (radical vs. ultra-radical) done in such patients. Methods: This was a retrospective analysis of all ovarian cancer patients who underwent cytoreductive surgery at our center from January 2009 to August 2013. The case records of these patients were reviewed and the demographic, disease-related and treatment-related data were extracted. Results: Fifty-fivepatients were identified. Ten (18.2%) patients underwent primary cytoreduction while 45 patients had (81.8%) interval cytoreduction. The resections achieved were optimal in 50 patients (90.9%) and suboptimal in five patients (9.1%). The postoperative median blood loss was 400 (350–600) mL. The median time interval for surgery was 4.0 h (3–5 h). The type of resection achieved (optimal vs. suboptimal) was the only factor affecting the progression free survival (PFS) (Hazard ratio = 0.08 95% confidence interval 0.02–0.3). There was no significant difference in postoperative morbidity in patients undergoing the ultra-radical surgery as compared to those who underwent radical surgery. Conclusion: Optimal cytoreduction may improve PFS in advanced ovarian cancer patients and needs to be done even if it mandates an ultra-radical surgery.


Keywords: Advanced, extensive, morbidity, ovarian cancer, surgery, ultra radical


How to cite this article:
Dessai S B, Patil V M, Chakraborty S, Babu S, Bhattacharjee A, Nayanar S, Vikram S, Balasubramanian S. An audit of cytoreductive surgeries in ovarian cancer from a rural based cancer center. Indian J Cancer 2016;53:284-7

How to cite this URL:
Dessai S B, Patil V M, Chakraborty S, Babu S, Bhattacharjee A, Nayanar S, Vikram S, Balasubramanian S. An audit of cytoreductive surgeries in ovarian cancer from a rural based cancer center. Indian J Cancer [serial online] 2016 [cited 2020 Mar 31];53:284-7. Available from: http://www.indianjcancer.com/text.asp?2016/53/2/284/197743



 » Introduction Top


The management of advanced stage carcinoma ovary remains a challenge with a reported median survival ranging between 22 and 30 months.[1],[2] Though, the surgery remains the mainstay of treatment, role of extent of surgery (ultra-radical vs. radical) is not defined.[3] Proponents of both ultra-radical and radical surgeries exist. Those in favor of the ultra-radical surgery, suggest that the presence residual tumor postsurgery correlates with poor survival.[4],[5],[6] The relation between postsurgery residual disease and survival is well described with at least one study showing that there is a reduction in survival with increasing size of residual disease.[5] On the other hand, proponents of standard surgery point out that extent of disease in peritoneum is related to the aggressive biology of the tumor and in such cases extensive surgery done for achievement of optimal cytoreduction is unlikely to help.[7] Further, it's suggested that optimal surgery is mostly achieved in cases with less advanced peritoneal disease.[7] A retrospective analysis of 194 patients did suggest that ultra-radical surgery may be associated with an improvement in overall survival.[6]

Ours is a rural based cancer center located in Kerala, India. Majority of our ovarian cancer patient present with advanced stage disease and we follow a surgical philosophy of attempting to achieve optimal cytoreduction, which may necessitate an ultra-radical resection in several cases. We hereby present an audit of all cases of advanced ovarian cancers, who underwent cytoreductive surgery at our center in order to elucidate the impact of optimal cytoreduction on their subsequent outcome.


 » Materials and Methods Top


This was a retrospective analysis of all ovarian cancer patients who underwent cytoreductive surgery at our center from January 2009 to August 2013. The case numbers were identified from the operation theatre records. The case records of these patients were then retrieved, and the following details were noted. The demographic pattern, details about diagnosis, staging details, CA-125, details about surgery, postoperative complications, details of neoadjuvant and adjuvant chemotherapy, date of progression and date of death were noted.

As per the criteria proposed by Ang et al.,[3] the surgeries were divided into either:

  • Radical or standard surgery: Hysterectomy, bilateral salpingo-oophorectomy, omentectomy, removal of enlarged pelvic or paraaortic lymph nodes and pelvic peritonectomy
  • Ultra-radical: Standard surgery + either one of the following:
  • Extensive peritonectomy including the partial diaphragmatic resection
  • Splenectomy
  • Sub capsular liver deposit excision
  • Requirement of bowel resection for removal of disease
  • Requirement of gastric resection for removal of disease.


The surgical procedures were further classified as optimal or suboptimal cytoreduction. Optimal cytoreduction was defined as no evidence of macroscopically visible disease postsurgical excision. The postoperative complications were graded according to the common terminology criteria for adverse events version 4.02.

Patients underwent further adjuvant chemotherapy if they had not completed six cycles of neoadjuvant chemotherapy prior to surgery or they had gross residual disease. The number of cycles of adjuvant chemotherapy was decided individually for each patient with an aim to deliver a total of six cycles (inclusive of neoadjuvant chemotherapy). Post chemotherapy patients were followed up at 3 monthly intervals for first 2 years, 4 monthly intervals for 3rd year and at 6 monthly intervals thereafter till 5 years. At each visit serum, CA-125 was done along with complete physical examination. Imaging was obtained only in case of the rise in CA-125 or in case of suspicious clinical findings or patient symptoms.

Statistical analysis

Statistical Package for the Social Sciences version 16 was used for analysis. Descriptive statistics reported include frequencies for categorical variables and median with an interquartile range for continuous variables. The progression-free survival (PFS) was calculated from the date of surgery till either biochemical or morphological progression. Progression was defined based on CA-125, symptom and RECIST criteria as defined previously by Rustin et al.[8] Wilcoxon Mann-Whitney U test was used for finding significant differences in the frequencies of categorical variables among patients undergoing radical versus ultra-radical surgery. Continuous variables were compared using the Student's t-test after checking for normality assumptions. Kaplan–Meier survival analysis was used for estimation of PFS. Cox proportional hazard regression with forward logistic regression method was used for multivariate analysis for factors affecting PFS. P < 0.05 were considered as significant.


 » Results Top


Baseline details and prior therapy

There were 65 cytoreductive surgeries performed during the time period. Two patients were excluded as surgery was done in palliative setting and eight patients were excluded as they had stage IA disease. The baseline details of 55 patients analyzed are provided in [Table 1].
Table 1: Baseline details of all 55 patients

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There were 27 (49.1%) patient who had received some form of prior therapy before presenting at our center. Among these treatment was surgical in 23 (41.8%) of patients, in the form of a hysterectomy in 15 (27.3%), only biopsy in 7 (12.7%) and oophorectomy in 1 (1.8%) patient. Neoadjuvant chemotherapy (NACT) prior to coming to the center was received by 9 (16.4%) patients.

Treatment at center

Ten (18.2%) patients underwent primary cytoreduction and 45 (81.8%) interval cytoreduction at our center. In the 45 patients receiving neoadjuvant chemotherapy, 43 had extensive disease which would have required debulking surgery with a potential R1 resection while two had intra-hepatic metastases.

The NACT regimens received were paclitaxel and carboplatin in 44 (80.0%) of patients and single agent carboplatin in 1 (1.8%) of patients. The median numbers of cycles delivered were 4.[3],[4],[5],[6]

Radical and ultra-radical surgery were performed in 42 (76.4%) and 13 (23.6%) patients respectively. The resections achieved were optimal in 50 patients (90.9%) and suboptimal in five patients (9.1%). The median postoperative median blood loss was 400 (interquartile range [IQR]: 350–600) mL. The median time interval for surgery was 4.0 h (IQR: 3–5 h). [Table 2] depicts postoperative complication rates in these patients reported using the maximum grade approach. [Table 3] shows the comparison of surgical parameters and serious toxicities in patients undergoing a radical versus ultra-radical surgery.
Table 2: Surgical morbidity details in accordance with National Cancer Institute (NCI) CTCAE version 4.02

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Table 3: Comparison between radical and ultra-radical surgery

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Thirty-seven patients underwent adjuvant chemotherapy after NACT and surgery. The regimen was paclitaxel and carboplatin in 33 (69.5%) of patients, gemcitabine cisplatin in two patients and single agent liposomal doxorubicin in one patient. The median numbers of cycles received were two (IQR: 2–3). The median total number chemotherapy cycles, including both neoadjuvant and adjuvant chemotherapy was six (IQR: 6-6).

All 10 patients undergoing adjuvant chemotherapy after primary cytoreduction received six cycles of paclitaxel and carboplatin.

Treatment outcomes

The median follow up of nonprogressed patients was 586 days (IQR 455–727 days). A total of 25 patients has experienced progression by last follow-up. The first sites of progression were the pelvic (n = 2), abdominal (n = 20), extra-abdominal (n = 3) and combined abdominal and extra-abdominal (n = 1). The overall median PFS was 804 days (26.8 months). The median PFS in radical surgery and ultra-radical surgery cohort were 804 days (26.8 months) and not reached respectively.(P = 0.969). Among tested variable age, Eastern cooperative oncology group performance status, body mass index, hemoglobin, albumin, creatinine, pretreatment CA-125, type of surgery (radical vs. ultra-radical), type of resection achieved (optimal vs. suboptimal) and total number of chemotherapy cycles, only factor affecting the PFS was type of resection achieved (Hazard ratio 0.08 95% confidence interval [CI] 0.02–0.3). The patients who underwent optimal resection had a median PFS of 915 days (30.5 months) (95% CI 693.6–1136.4) versus 296 days (9.9 months) (263.8–328.2) in patients undergoing suboptimal resection (P = 0.0001) [Figure 1].
Figure 1: Estimated progression free survival of patients according to the type of resection

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 » Discussion Top


Achieving a cytoreduction with no visible macroscopic disease is the primary aim of surgery in ovarian cancer.[9] One large randomized controlled trial has shown that debulking surgery after induction chemotherapy results in a significant improvement in the overall survival as compared to no surgery.[10] In the setting of primary cytoreductive surgery also there is abundant retrospective data on the importance of achieving an optimal cytoreduction through a maximal resection.[4],[5],[6],[11],[12],[13],[14] Concerns however remain regarding the impact of doing ultra-radical resection in terms of increased operative time, blood loss and morbidity.[9] Proponents of a conservative surgical approach argue that the aggressive biology of the disease is the primary determining factor in the overall prognosis, and the extent of surgical resection required is a surrogate variable for this aggressiveness.[15],[16] The differing philosophies in the surgical management mean that surgical practices vary widely in differing institutions indicating a need for standardization.[9] In the present study, the median PFS was 26.8 months which are encouraging when compared to the results reported in recent trials in advanced epithelial ovarian cancers (10–12 months).[1],[2] It should be noted that the proportion of patients undergoing suboptimal cytoreduction in these studies ranged from 30% to 90% (differing according to institute and country), which was much higher than that reported in the present series.[1],[2] We believe that this higher PFS seen in our cohort of patients may be related to the higher rates of optimal cytoreduction done in our patients. Though there was no difference in PFS between radical and ultra-radical surgery patients. All these patients who underwent ultra-radical had higher disease burden and if it hadn't been for an ultra-radical surgery these patients would have had suboptimal resections.

In our setup doing an ultra-radical surgery or radical surgery resulted in no significant difference in morbidity, mortality or blood loss. The rates of major postoperative complications were similar to that reported in recently conducted a randomized controlled trial which attests to the safety of our present resection policy.[1],[2] However, the median time of surgery in patients undergoing ultra-radical resections was increased by 2 h when compared to those who underwent radical resection. In general also the median operative time in our series was higher than that reported in the trial conducted by Vergote et al.[1] The reason for this may be the practice of performing routine para-aortic lymph node dissection at our center. There is some evidence in the literature that in optimally debulked patients paraaortic lymph node dissection improves PFS.[17],[18] However it's not routinely performed at all centers under the assumption that it lacks significant survival benefit.[18]

This study has its limitations. The small sample size, retrospective design and the heterogeneous nature of treatment received by the patient, make it difficult to draw definitive conclusions. However, the present study illustrates the importance of achieving an optimal cytoreduction in patients with advanced ovarian cancers and its impact on PFS.


 » Conclusion Top


Optimal cytoreduction improves PFS in advanced ovarian cancer patients, needs to be done even if it mandates an ultra-radical surgery. Ultra-radical surgery does not result in a significant increase in the postoperative morbidity as compared to standard radical surgery.


 » Acknowledgment Top


All staff of MCC.

 
 » References Top

1.
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;363:943-53.  Back to cited text no. 1
    
2.
Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener HC, Lopes T, et al. Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: Results from the MRC CHORUS trial. Am Soc Clin Oncol Meet Abstr 2013;31 15 suppl: 5500.  Back to cited text no. 2
    
3.
Ang C, Chan KK, Bryant A, Naik R, Dickinson HO. Ultra-radical (extensive) surgery versus standard surgery for the primary cytoreduction of advanced epithelial ovarian cancer. Cochrane Database Syst Rev 2011;Apr 13; (4):CD007697.  Back to cited text no. 3
    
4.
Eisenkop SM, Friedman RL, Wang HJ. Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: A prospective study. Gynecol Oncol 1998;69:103-8.  Back to cited text no. 4
    
5.
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;20:1248-59.  Back to cited text no. 5
    
6.
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.  Back to cited text no. 6
    
7.
Crawford SC, Vasey PA, Paul J, Hay A, Davis JA, Kaye SB. Does aggressive surgery only benefit patients with less advanced ovarian cancer? Results from an international comparison within the SCOTROC-1 Trial. J Clin Oncol 2005;23:8802-11.  Back to cited text no. 7
    
8.
Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M, Thigpen T, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer 2011;21:419-23.  Back to cited text no. 8
    
9.
Markman M. Concept of optimal surgical cytoreduction in advanced ovarian cancer: A brief critique and a call for action. J Clin Oncol 2007;25:4168-70.  Back to cited text no. 9
    
10.
van der Burg ME, van Lent M, Buyse M, Kobierska A, Colombo N, Favalli G, et al. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med 1995;332:629-34.  Back to cited text no. 10
    
11.
Eisenkop SM, Spirtos NM, Friedman RL, Lin WC, Pisani AL, Perticucci S. Relative influences of tumor volume before surgery and the cytoreductive outcome on survival for patients with advanced ovarian cancer: A prospective study. Gynecol Oncol 2003;90:390-6.  Back to cited text no. 11
    
12.
Chi DS, Eisenhauer EL, Lang J, Huh J, Haddad L, Abu-Rustum NR, et al. What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)? Gynecol Oncol 2006;103:559-64.  Back to cited text no. 12
    
13.
Elattar A, Bryant A, Winter-Roach BA, Hatem M, Naik R. Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database Syst Rev 2011; Aug 10;(8):CD007565.  Back to cited text no. 13
    
14.
Luyckx M, Leblanc E, Filleron T, Morice P, Darai E, Classe JM, et al. Maximal cytoreduction in patients with FIGO stage IIIC to stage IV ovarian, fallopian, and peritoneal cancer in day-to-day practice: A retrospective French multicentric study. Int J Gynecol Cancer 2012;22:1337-43.  Back to cited text no. 14
    
15.
Hoskins WJ, Bundy BN, Thigpen JT, Omura GA. The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage III epithelial ovarian cancer: A gynecologic oncology group study. Gynecol Oncol 1992;47:159-66.  Back to cited text no. 15
    
16.
Hunter RW, Alexander ND, Soutter WP. Meta-analysis of surgery in advanced ovarian carcinoma: Is maximum cytoreductive surgery an independent determinant of prognosis? Am J Obstet Gynecol 1992;166:504-11.  Back to cited text no. 16
    
17.
Panici PB, Maggioni A, Hacker N, Landoni F, Ackermann S, Campagnutta E, et al. Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: A randomized clinical trial. J Natl Cancer Inst 2005;97:560-6.  Back to cited text no. 17
    
18.
Camara O, Sehouli J. Controversies in the management of ovarian cancer – Pros and cons for lymph node dissection in ovarian cancer. Anticancer Res 2009;29:2837-43.  Back to cited text no. 18
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 Carboplatin/paclitaxel
Reactions Weekly. 2017; 1643(1): 70
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