Skip to main content
Top
Published in: Annals of Surgical Oncology 1/2020

01-01-2020 | Metastasis | Peritoneal Surface Malignancy

Colorectal Peritoneal Metastases Treated by Perioperative Systemic Chemotherapy and Cytoreductive Surgery With or Without Mitomycin C-Based HIPEC: A Comparative Study Using the Peritoneal Surface Disease Severity Score (PSDSS)

Authors: Dario Baratti, MD, Shigeki Kusamura, PhD, Norfarizan Azmi, MD, Marcello Guaglio, MD, Matteo Montenovo, MD, Marcello Deraco, MD

Published in: Annals of Surgical Oncology | Issue 1/2020

Login to get access

Abstract

Background

The Prodige-7 trial has questioned the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal metastases from colorectal cancer (CRC-PM).

Patients and Methods

We compared a prospectively collected group of 48 patients undergoing oxaliplatin/irinotecan-based perioperative systemic chemotherapy (s-CT) with targeted agents, and cytoreductive surgery (CRS) (no-HIPEC group) with 48 controls undergoing the same perioperative s-CT and CRS/HIPEC (HIPEC group). Patients were matched (1:1) according to the Peritoneal Surface Disease Severity Score, completeness of cytoreduction, history of extraperitoneal disease (EPD), and Peritoneal Cancer Index.

Results

The groups were comparable, except for a higher number of patients in the HIPEC group with World Health Organization performance status 0, pN2 stage primary tumor, and treated with preoperative s-CT. Forty-one patients in the no-HIPEC group and 43 patients in the HIPEC group had optimal comprehensive treatment (P = 0.759), defined as complete cytoreduction of PM and margin-negative EPD resection. Median follow-up was 31.6 months in the no-HIPEC group and 39.9 months in the HIPEC group. Median overall survival was 39.3 months in the no-HIPEC group and 34.8 months in the HIPEC group (P = 0.702). In the two groups, severe morbidity occurred in 14 (29.2%) and 13 (27.1%) patients, respectively (P = 1.000), with no operative deaths. On multivariate analysis, left-sided primary and curative treatment independently correlated with better survival while HIPEC did not (hazard ratio 0.73; 95% confidence interval 0.47–1.15; P = 0.178).

Conclusions

Our results confirmed that, in selected patients, perioperative s-CT and surgical treatment of CRC-PM resulted in unexpectedly high survival rates. Mitomycin C-based HIPEC did not increase morbidity but did not impact prognosis.
Literature
1.
go back to reference Lemmens VE, Klaver YL, Verwaal VJ, et al. Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study. Int J Cancer. 2011;128:2717–25.CrossRef Lemmens VE, Klaver YL, Verwaal VJ, et al. Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study. Int J Cancer. 2011;128:2717–25.CrossRef
2.
go back to reference Segelman J, Granath F, Holm T, et al. Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2012;99:699–705.CrossRef Segelman J, Granath F, Holm T, et al. Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2012;99:699–705.CrossRef
3.
go back to reference Baratti D, Kusamura S, Pietrantonio F, Guaglio M, Niger M, Deraco M. Progress in treatments for colorectal cancer peritoneal metastases during the years 2010–2015: a systematic review. Crit Rev Oncol Hematol. 2016;100:209–22.CrossRef Baratti D, Kusamura S, Pietrantonio F, Guaglio M, Niger M, Deraco M. Progress in treatments for colorectal cancer peritoneal metastases during the years 2010–2015: a systematic review. Crit Rev Oncol Hematol. 2016;100:209–22.CrossRef
4.
go back to reference Franko J, Shi Q, Goldman CD, 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;30:263–7.CrossRef Franko J, Shi Q, Goldman CD, 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;30:263–7.CrossRef
5.
go back to reference Klaver YL, Simkens LH, Lemmens VE, et al. Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy. Eur J Surg Oncol. 2012;38:617–23.CrossRef Klaver YL, Simkens LH, Lemmens VE, et al. Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy. Eur J Surg Oncol. 2012;38:617–23.CrossRef
6.
go back to reference Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27:681–85.CrossRef Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27:681–85.CrossRef
7.
go back to reference Elias D, Gilly F, Boutitie F, 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;28:63–8.CrossRef Elias D, Gilly F, Boutitie F, 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;28:63–8.CrossRef
8.
go back to reference Sugarbaker PH, Ryan DP. Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol. 2012;13:e362–9.CrossRef Sugarbaker PH, Ryan DP. Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol. 2012;13:e362–9.CrossRef
9.
go back to reference Verwaal VJ, van Ruth S, de Bree E, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737–43.CrossRef Verwaal VJ, van Ruth S, de Bree E, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737–43.CrossRef
10.
go back to reference Gremonprez F, Willaert W, Ceelen W. Intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis: review of animal models. J Surg Oncol. 2014;109:110–6.CrossRef Gremonprez F, Willaert W, Ceelen W. Intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis: review of animal models. J Surg Oncol. 2014;109:110–6.CrossRef
11.
go back to reference Yang XJ, Huang CQ, Suo T, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011;18:1575–81.CrossRefPubMed Yang XJ, Huang CQ, Suo T, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011;18:1575–81.CrossRefPubMed
12.
go back to reference van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378:230–40.CrossRef van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378:230–40.CrossRef
14.
go back to reference Ceelen W. HIPEC with oxaliplatin for colorectal peritoneal metastasis: The end of the road? Eur J Surg Oncol. 2019;45:400–2.CrossRef Ceelen W. HIPEC with oxaliplatin for colorectal peritoneal metastasis: The end of the road? Eur J Surg Oncol. 2019;45:400–2.CrossRef
15.
go back to reference Elias D, Delperro JR, Sideris L, et al. Treatment of peritoneal carcinomatosis from colorectal cancer: impact of complete cytoreductive surgery and difficulties in conducting randomized trials. Ann Surg Oncol. 2004;11:518–21.CrossRef Elias D, Delperro JR, Sideris L, et al. Treatment of peritoneal carcinomatosis from colorectal cancer: impact of complete cytoreductive surgery and difficulties in conducting randomized trials. Ann Surg Oncol. 2004;11:518–21.CrossRef
16.
go back to reference Scaringi S, Leo F, Canonico G, Batignani G, Ficari F, Tonelli F. The role of cytoreductive surgery alone for the treatment of peritoneal carcinomatosis of colorectal origin: a retrospective analysis with regard to multimodal treatments. Hepatogastroenterology. 2009;56:650–5. Scaringi S, Leo F, Canonico G, Batignani G, Ficari F, Tonelli F. The role of cytoreductive surgery alone for the treatment of peritoneal carcinomatosis of colorectal origin: a retrospective analysis with regard to multimodal treatments. Hepatogastroenterology. 2009;56:650–5.
17.
go back to reference Mulsow J, Merkel S, Agaimy A, Hohenberger W. Outcomes following surgery for colorectal cancer with synchronous peritoneal metastases. Br J Surg. 2011;98:1785–91.CrossRef Mulsow J, Merkel S, Agaimy A, Hohenberger W. Outcomes following surgery for colorectal cancer with synchronous peritoneal metastases. Br J Surg. 2011;98:1785–91.CrossRef
18.
go back to reference Kobayashi H, Enomoto M, Higushi T, et al. Validation and clinical use of the Japanese classification of colorectal carcinomatosis: benefit of surgical cytoreduction, even without intraperitoneal chemotherapy. Dig Surg. 2010;27:473–80.CrossRef Kobayashi H, Enomoto M, Higushi T, et al. Validation and clinical use of the Japanese classification of colorectal carcinomatosis: benefit of surgical cytoreduction, even without intraperitoneal chemotherapy. Dig Surg. 2010;27:473–80.CrossRef
19.
go back to reference Kobayashi H, Kotak, K., Sugihara, K, et al. Outcomes of surgery without HIPEC for synchronous peritoneal metastasis from colorectal cancer: data from a multi-center registry. Int J Clin Oncol. 2014;19:98–105.CrossRef Kobayashi H, Kotak, K., Sugihara, K, et al. Outcomes of surgery without HIPEC for synchronous peritoneal metastasis from colorectal cancer: data from a multi-center registry. Int J Clin Oncol. 2014;19:98–105.CrossRef
20.
go back to reference Pelz O, Stojadinovic A, Nissan A, Hohenberger W, Esquivel J. Evaluation of a Peritoneal Surface Disease Severity Score in patients with colon cancer and peritoneal dissemination. J Surg Oncol. 2009;99:9–15.CrossRef Pelz O, Stojadinovic A, Nissan A, Hohenberger W, Esquivel J. Evaluation of a Peritoneal Surface Disease Severity Score in patients with colon cancer and peritoneal dissemination. J Surg Oncol. 2009;99:9–15.CrossRef
21.
go back to reference Chua TC, Morris DL, Saxena A, et al. Influence of modern systemic therapies as adjunct to cytoreduction and perioperative intraperitoneal chemotherapy for patients with colorectal peritoneal carcinomatosis: a multicenter study. Ann Surg Oncol. 2011;18:1560-7.CrossRef Chua TC, Morris DL, Saxena A, et al. Influence of modern systemic therapies as adjunct to cytoreduction and perioperative intraperitoneal chemotherapy for patients with colorectal peritoneal carcinomatosis: a multicenter study. Ann Surg Oncol. 2011;18:1560-7.CrossRef
22.
go back to reference Prada-Villaverde A, Esquivel J, Lowy AM, et al. The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with mitomycin C versus oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery. J Surg Oncol. 2014;110:779–85.CrossRef Prada-Villaverde A, Esquivel J, Lowy AM, et al. The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with mitomycin C versus oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery. J Surg Oncol. 2014;110:779–85.CrossRef
23.
go back to reference Baratti D, Kusamura S, Iusco D, et al. Postoperative complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy affect long-term outcome of patients with peritoneal metastases from colorectal cancer: a two-center study of 101 patients. Dis Colon Rectum. 2014;57:858–68.CrossRef Baratti D, Kusamura S, Iusco D, et al. Postoperative complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy affect long-term outcome of patients with peritoneal metastases from colorectal cancer: a two-center study of 101 patients. Dis Colon Rectum. 2014;57:858–68.CrossRef
24.
go back to reference Baratti D, Kusamura S, Iusco D, et al. Should a history of extra-peritoneal disease be a contraindication to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer peritoneal metastases? Dis Colon Rectum. 2018;61:1026–34.CrossRef Baratti D, Kusamura S, Iusco D, et al. Should a history of extra-peritoneal disease be a contraindication to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer peritoneal metastases? Dis Colon Rectum. 2018;61:1026–34.CrossRef
25.
go back to reference Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–422.CrossRef Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–422.CrossRef
26.
go back to reference Deraco M, Baratti D, Kusamura S, Laterza B, Balestra MR. Surgical technique of parietal and visceral peritonectomy for peritoneal surface malignancies. J Surg Oncol. 2009;100:321–8.CrossRef Deraco M, Baratti D, Kusamura S, Laterza B, Balestra MR. Surgical technique of parietal and visceral peritonectomy for peritoneal surface malignancies. J Surg Oncol. 2009;100:321–8.CrossRef
27.
go back to reference Jaquet P, Sugarbaker PH. Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J Exp Clin Cancer Res. 1996;15:49–58. Jaquet P, Sugarbaker PH. Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J Exp Clin Cancer Res. 1996;15:49–58.
29.
go back to reference Désolneux G, Mazière C, Vara J, et al. Cytoreductive surgery of colorectal peritoneal metastases: outcomes aftercomplete cytoreductive surgery and systemic chemotherapy only. PLoS One. 2015;10, e0122816.CrossRefPubMed Désolneux G, Mazière C, Vara J, et al. Cytoreductive surgery of colorectal peritoneal metastases: outcomes aftercomplete cytoreductive surgery and systemic chemotherapy only. PLoS One. 2015;10, e0122816.CrossRefPubMed
30.
go back to reference Bushati M, Rovers KP, Sommariva A, et al. The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI). Eur J Surg Oncol. 2018;44:1942–48.CrossRef Bushati M, Rovers KP, Sommariva A, et al. The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI). Eur J Surg Oncol. 2018;44:1942–48.CrossRef
31.
go back to reference Hompes D, D’Hoore A, Wolthuis A, et al. The use of oxaliplatin or mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. J Surg Oncol. 2014;109:527–32.CrossRef Hompes D, D’Hoore A, Wolthuis A, et al. The use of oxaliplatin or mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. J Surg Oncol. 2014;109:527–32.CrossRef
32.
go back to reference Leung V, Huo YR, Liauw W, Morris DL. Oxaliplatin versus mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis. Eur J Surg Oncol. 2017;43:144–9.CrossRef Leung V, Huo YR, Liauw W, Morris DL. Oxaliplatin versus mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis. Eur J Surg Oncol. 2017;43:144–9.CrossRef
33.
go back to reference Votanopoulos K, Ihemelandu C, Shen P, Stewart J, Russell G, Levine EA. A comparison of hematologic toxicity profiles after heated intraperitoneal chemotherapy with oxaliplatin and mitomycin C. J Surg Res. 2013;179:e133–9.CrossRef Votanopoulos K, Ihemelandu C, Shen P, Stewart J, Russell G, Levine EA. A comparison of hematologic toxicity profiles after heated intraperitoneal chemotherapy with oxaliplatin and mitomycin C. J Surg Res. 2013;179:e133–9.CrossRef
34.
go back to reference van Eden WJ, Kok NFM, Woensdregt K, Huitema ADR, Boot H, Aalbers AGJ. Safety of intraperitoneal Mitomycin C versus intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis of colorectal cancer undergoing cytoreductive surgery and HIPEC. Eur J Surg Oncol. 2018;44:220–7.CrossRef van Eden WJ, Kok NFM, Woensdregt K, Huitema ADR, Boot H, Aalbers AGJ. Safety of intraperitoneal Mitomycin C versus intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis of colorectal cancer undergoing cytoreductive surgery and HIPEC. Eur J Surg Oncol. 2018;44:220–7.CrossRef
35.
go back to reference Baratti D, Kusamura S, Iusco D, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of primary curative surgery in patients with colorectal cancer at high risk for metachronous peritoneal metastases. Ann Surg Oncol. 2017;24:167–75.CrossRef Baratti D, Kusamura S, Iusco D, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of primary curative surgery in patients with colorectal cancer at high risk for metachronous peritoneal metastases. Ann Surg Oncol. 2017;24:167–75.CrossRef
36.
go back to reference Ubink I, Bolhaqueiro ACF, Elias SG, et al. Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy. Br J Surg. [Epub ahead of print]. Ubink I, Bolhaqueiro ACF, Elias SG, et al. Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy. Br J Surg. [Epub ahead of print].
Metadata
Title
Colorectal Peritoneal Metastases Treated by Perioperative Systemic Chemotherapy and Cytoreductive Surgery With or Without Mitomycin C-Based HIPEC: A Comparative Study Using the Peritoneal Surface Disease Severity Score (PSDSS)
Authors
Dario Baratti, MD
Shigeki Kusamura, PhD
Norfarizan Azmi, MD
Marcello Guaglio, MD
Matteo Montenovo, MD
Marcello Deraco, MD
Publication date
01-01-2020
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 1/2020
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07935-2

Other articles of this Issue 1/2020

Annals of Surgical Oncology 1/2020 Go to the issue