Fetsych and Revura: Efficacy of Surgical Treatment of Peritoneal Carcinomatosis in Patients with Colorectal Cancer



Problem statement and analysis of the recent research

Colorectal cancer (CRC) is one of the most common cancers worldwide. In Ukraine, about 20,000 new cases of CRC are registered every year [1]. Substantial contribution to high mortality rate in CRC is caused by late diagnosis of the disease, the development of recurrences and metastases after radical treatment. Peritoneal carcinomatosis (PC) is the least favorable form of the disease, which has been treated with palliative chemotherapy and symptomatic treatment for a long time [2]. However, over the last twenty years, there has been rapid growth of a new approach involving aggressive surgical treatment to prolong survival time of patients with CRC metastases, including peritoneal ones [3-5]. In selected patients with resectable disease cytoreductive surgery is performed, which includes the removal of the bowel primary tumor and peritoneal metastases in combination with chemotherapy [6].

The objective of the research was to evaluate and compare the efficacy of cytoreductive surgery, chemotherapy and symptomatic treatment of patients with colorectal cancer and peritoneal carcinomatosis.

Materials and methods

The analysis of treatment of patients with CRC and PC being treated in Lviv State Oncological Regional Treatment and Diagnostic Center during 2008-2015 was made. The study included patients with synchronous peritoneal dissemination found when diagnosing CRC, and those who developed metachronous peritoneal metastases as a manifestation of the disease progression during follow-up after previous treatment.

All patients were divided into 3 groups depending on the method of treatment being used after the detection of PC. Group I consisted of patients who underwent cytoreductive surgery. Group II included patients treated with palliative chemotherapy. To treat patients of Group III only symptomatic methods of treatment were used.

Statistical analysis of the results was performed using STATISTICA 10 software (StatSoft Inc.). The age of patients was given as μ ± σ, where μ was the mean value and σ was the standard deviation. Overall survival was analyzed using cumulative survival curves by the Kaplan-Meier method; median overall survival (Me) was calculated. The significance of the difference in survival between groups of patients was assessed using nonparametric the Gehan-Wilcoxon test.

Results and Discussion

The study included 93 patients with CRC and PC. There were 52 (55.9%) women and 41 (44.1%) men. The age of patients ranged from 24 to 81 years with the mean age of 61.3±10.84 years.

Thirty (32.3%) patients had rectal cancer and 63 (67.7%) patients had colon cancer. Synchronous PC was diagnosed in 64 (68.8%) patients, 29 (31.2%) patients had metachronous peritoneal metastases.

Cytoreductive surgery involving partial peritonectomy of regions of the peritoneum affected by metastases was performed in 44 patients of Group I. Primary tumor was simultaneously removed in 30 (68.2%) patients of this group with synchronous PC, and local recurrence was removed in 5 (11.4%) patients with metachronous PC. Cytoreductive surgery included liver resection in 4 (9.1%) patients with solitary or limited number of hepatic metastases. Palliative chemotherapy was performed in 30 (68.2%) patients of Group I 3-4 weeks after surgery.

Patients, who did not undergo cytoreductive surgery due to extensive unresectable disease, received palliative chemotherapy (Group II, 27 patients) and in the presence of contraindications to chemotherapy symptomatic treatment only (Group III, 22 patients).

Overall survival of patients with CRC and PC was estimated depending on the different method of treatment in each group. Overall survival was found to be dependent on the method of treatment (Fig. 1). In patients of Group I who underwent cytoreductive surgery median overall survival was 15.5 months, in patients of Group II who received palliative chemotherapy it was 5.9 months, and in patients of Group III who received symptomatic therapy median overall survival was 3.1 months (p<0.0001). These results indicate that the best long-term outcomes of treatment were achieved in patients of Group I treated with cytoreductive surgery.

Fig. 1.

Overall survival of patients of Groups I, II, III depending on treatment method

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Additionally, overall survival was analyzed among patients of Group I depending on whether chemotherapy was performed after surgery (Fig. 2).

Fig. 2.

Overall survival of patients in Group I who underwent cytoreductive surgery depending on whether palliative chemotherapy was performed

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Median survival of patients who were treated with combined therapy was found to be 16.5 months, while in patients who did not undergo chemotherapy after surgery it was 14.2 months. However, the difference in survival was not statistically significant (p=0.12). Thus, the major impact on survival extension in patients with CRC and PC belongs to the surgical component in case of combined approach, and the effect of chemotherapy was not revealed.

Cytoreductive surgery was described by P. Sugabaker in 1995 as a method of local control of metastatic disease [7]. The rationale for this treatment method of PC is based on the features of peritoneal metastases as locoregional spread of tumor [8]. Currently, combined approach involving cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion and systemic chemotherapy is considered as the most effective treatment of PC providing median survival of 30.1 months [9]. However, the studies on the effectiveness of surgery without intraperitoneal chemotherapy are scarce. Y. Klaver et al. reported the results of the research similar to the given one which demonstrate the ability of surgical resection to improve the survival of patients with PC (median survival of 55 weeks) compared to symptomatic surgeries (median survival of 12 weeks) [10]. However, these patients underwent palliative resection of the primary tumor without removing peritoneal metastases, while in our study surgery was aimed at the maximally complete removal of all macroscopic tumor foci.

Thus, long-term outcomes in patients with CRC and PC suggest that cytoreductive surgery is an effective method of treatment.

Conclusions

Overall survival of patients with CRC and PC was higher when treated with cytoreductive surgery compared to palliative chemotherapy and symptomatic treatment. Palliative chemotherapy had no effect on survival after cytoreductive surgery for PC.

Prospects for further research

The effectiveness of treatment of patients with CRC and PC using cytoreductive surgery in combination with hyperthermic intraperitoneal chemoperfusion requires further investigation.

References

1 

O Kolesnik, Z Fedorenko, L Hulak, Yu Mykhaylovych. Bulletin of National Cancer Registry of Ukraine № 17, Cancer in Ukraine 2014-2015. O Kolesnik, editor. Kyiv: National Cancer Institute; 2016. 146 p.

2 

J Franko, Q Shi, CD Goldman, BA Pockaj, GD Nelson, RM Goldberg, et al. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: A pooled analysis of North Central Cancer Treatment Group phase III trials N9741 and N9841. J Clin Oncol. 2012;30(3):263-7. doi:10.1200/JCO.2011.37.1039

3 

M Zubaryev, T Fetsych, O Kovaliov, K Kovaliov, R Yarema, A Revura, et al. Efficacy of liver resection combined with chemotherapy in patients with liver metastases from colorectal cancer compared to chemotherapy alone and symptomatic treatment. Praktychna medytsyna. 2010;XVI(5):75-87.

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R Yarema, T Fetsych, O Glehen, FN Gilly, M Ohorchak, M Zubaryev. Intraperitoneal disseminated cancer: the end of the era of skepticism? Onkolohiia. 2013;15(2):88-95.

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D Elias, F Quenet, D Goere. Current status and future directions in the treatment of peritoneal dissemination from colorectal carcinoma. Surg Oncol Clin N Am. 2012;21(4):611-23. doi:10.1016/j.soc.2012.07.014

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PH Sugarbaker. Early intervention for treatment and prevention of colorectal carcinomatosis: a plan for individualized care. Surg Oncol Clin N Am. 2012;21(4):689-703. doi:10.1016/j.soc.2012.07.009

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PH Sugarbaker. Peritonectomy procedure. Ann Surg. 1995;221(1):29-42. doi:10.1097/00000658-199501000-00004

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F Coccolini, F Gheza, M Lotti, S Virzi, D Iusco, C Ghermandi, et al. Peritoneal carcinomatosis. World J Gastroenterol. 2013;19(41):6979-6994. doi:10.3748/wjg.v19.i41.6979

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D Elias, FN Gilly, F Boutitie, F Quenet, JM Bereder, B Mansvelt, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28(1):63-68. doi:10.1200/JCO.2009.23.9285

10 

YLB Klaver, LHJ Simkens, VEPP Lemmens, M Koopman, S Teerenstra, RP Bleichrodt, et al. Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy. Eur J Surg Oncol. 2012;38(7):617-623. doi:10.1016/j.ejso.2012.03.008



Copyright (c) 2017 T G Fetsych, A P Revura

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