Indian J Surg Oncol (June 2016) 7(2):137–138 DOI 10.1007/s13193-016-0493-5
EDITORIAL NOTES
Peritoneal Metastases: Prevention and Treatment Paul H. Sugarbaker 1
Received: 4 January 2016 / Accepted: 7 January 2016 / Published online: 4 February 2016 # Indian Association of Surgical Oncology 2016
Abstract Colorectal cancer is a surgicaly curable disease. It requires multimodality of treatment in Localy advanced and metastatic disease. Molecular markers like RAS mutation has brought in change in the mangement of metastatic disease. Nearly 15 to 20 % presents with peritonieal surface metastasis. The debate continues with systomic vs Cyutoreductive surgery with are without HIPEC. This article highlights management of peritoneal metastasis with special reference to prevention and treatment. Keywords Colorectal . Peritoneal surface . Cytoreductive . HIPEC
Open or laparoscopic surgery is an elegant and comprehensive treatment for a large majority (approximately 80 %) of patients who have a primary or colon or rectal cancer. Some * Paul H. Sugarbaker
1
Center for Gastrointestinal Malignancies, Program in Peritoneal Surface Oncology, MedStar Washington Hospital Center, Washington, DC, USA
colon cancer patients with positive lymph nodes show improved survival when adjuvant systemic chemotherapy is added to surgery [1]. Also, some selected rectal cancer patients will have decreased local control with preoperative radiation therapy plus surgery [2]. However, the mainstay for optimal treatment of a majority of patients with primary colon and rectal cancer is surgery alone. Both the patient and the surgeon expect a complete recovery and restoration of high quality of life following this approach. Unfortunately, a small percentage (estimated at 20 %) of patients will have a biologically aggressive colorectal cancer or a delay in diagnosis that causes peritoneal seeding to occur a some time in the natural history of the disease. Current standard of care demands that these patients be considered for an individualized treatment plan. A regimen of treatment that involves referral to the medical oncologist for systemic chemotherapy treatment as a definitive management plan does not meet the standard of care. Metastases may be diagnosed at two different time points in these colorectal cancer patients. First, they may be recognized prior to or at the time of the colorectal cancer resection, identified as SYNCHRONOUS peritoneal metastases. Alternatively, the peritoneal metastases may be diagnosed during follow-up, regarded as METACHRONOUS peritoneal metastases. The occurrence of peritoneal metastases with modern treatment algorithms is not, of necessity, a lethal clinical situation. An estimate of long-term survival in these two groups of patients with modern treatments is 30 % [3]. In the patients with synchronous diagnosis of peritoneal metastases some will have a small extent of abdominal or peritoneal spread so that the peritoneal metastases can be resected along with the primary malignancy. If that is possible all disease should be removed with the initial colorectal cancer resection. After a short course of systemic chemotherapy these patients must be considered for a second-look surgical exploration and cytoreductive surgery with perioperative
138
chemotherapy using hyperthermic intraperitoneal chemotherapy (HIPEC) [4]. If the synchronous disease is too extensive to be radically resected, then the surgical procedure for the primary colorectal cancer must be modified to allow for a comprehensive management plan. The surgery should be performed so minimal dissection and very limited opening of peritoneal incisions occurs. The peritoneum is the first line of defense against peritoneal dissemination [5]. Cancer cells implant approximately a hundred times more efficiently into a traumatized peritoneal surface as compared to an intact surface. Fibrin entrapment of cancer cells rendered unresectable at the time of a reoperative surgical procedure as a result of progression deep to the peritoneum must be avoided when dealing with extensive synchronous colorectal disease. When colorectal cancer patients are found to have disease recurrence diagnosed during follow-up, peritoneal metastases are frequent. Up to 50 % of patients with colorectal cancer recurrence will have peritoneal implants as part of the recurrent disease process. This is in contrast to only 8 % of patients with synchronous metastases. It is estimated that approximately 10 % of these patients will have isolated peritoneal metastases and become candidates for a potentially curative approach using cytoreductive surgery with HIPEC. Using current potentially curative treatment regimens, the estimate of long-term survival in this group of patients is 30 % [4]. There is a third group of patients that can be benefited by special treatments directed at the peritoneal surface component of colorectal cancer. These are patients at HIGH RISK for subsequent progression of peritoneal metastases. In these patients, peritoneal metastases cannot be documented at the time of primary colorectal cancer resection. However, these patients with serosal invasion of the primary cancer, positive margins of resection, and patients who have a perforation through the primary malignancy will develop peritoneal metastases greater than 50 % of the time [6]. Other gastrointestinal cancer patients have this high risk for subsequent peritoneal metastases. This includes gastric cancer patients with serosal invasion. Also, pancreas cancer patients resected for cure who have narrow or positive margins of resection are at high risk for local-regional recurrence with or without peritoneal metastases. Over 50 % of these gastric or pancreas cancer patients will manifest subsequent peritoneal metastases. These patients at high risk for subsequent peritoneal metastases are candidates for adjuvant treatment with HIPEC. In the past, these three groups of patients did not have special treatments designed to maximize their long-term survival. Systemic chemotherapy was used but improvement in disease-free survival was not frequent and a curative approach never materialized. In this special issue of the Indian Journal of Surgical Oncology these three groups of gastrointestinal cancer patients are the focus of the text. It critically evaluates the radiologic techniques that should be used to diagnose, anatomically locate,
Indian J Surg Oncol (June 2016) 7(2):137–138
and quantify peritoneal metastases. The role that laparoscopy can play to assist in patient selection is presented. The surgical treatments and special perioperative cancer chemotherapy for appendiceal, colorectal, and gastric cancer are thoroughly discussed by authors completely familiar with these treatments. Also, preoperative, intraoperative (anesthetic management), and postoperative management to maximize the safety of these advanced surgical procedures are included in this special issue. Patient selection for treatment must be a major focus in this new and important aspect of peritoneal surface oncology if high quality results are to be achieved. In summary, this special issue of the Indian Journal of Surgical Oncology presents to the cancer surgeon a new standard of care for selected patients. If we can select the appropriate patients and initiate safe and effective treatments, with current technology using cytoreductive surgery plus perioperative chemotherapy, large benefits will accrue. This approach to prevention and treatment of peritoneal metastases is a relatively new addition to the required surgical management strategies for gastrointestinal cancer. New concepts and treatment plans are being published on a weekly basis. Although current treatment plans are safe and effective and must be implemented at this point in time, new and improved approaches with added benefit are expected in the near future. A comprehensive approach to the prevention and treatment of peritoneal metastases presents a new frontier for progress in the management of gastrointestinal malignancy.
References 1.
Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG (2015) Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial. J Clin Oncol 33: 3733–3740 2. Fitzgerald TL, Brinkley J, Zervos EE (2011) Pushing the envelope beyond a centimeter in rectal cancer: Oncologic implications of a close, but negative margins. J Am Coll Surg 213:589–595 3. Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M, Barone R, Yonemura Y, Cavaliere F, Quenet F, Gutman M, Tentes AA, Lorimier G, Bernard JL, Bereder JM, Porcheron J, Gomez-Portilla A, Shen P, Deraco M, Rat P (2004) Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: A multi-institutional study. J Clin Oncol 22(16):3284–3292 4. Elias D, Goéré D, Di Pietrantonio D, Boige V, Malka D, KohnehShahri N, Dromain C, Ducreux M (2008) Results of systematic second-look surgery in patients at high risk of developing colorectal peritoneal carcinomatosis. Ann Surg 247(3):445–450 5. Sugarbaker PH (2007) Peritoneum as the first line of defense in carcinomatosis. J Surg Oncol 95(2):93–96 6. Honoré C, Goéré D, Souadka A, Dumont F, Elias D (2013) Definition of patients presenting a high risk of developing peritoneal carcinomatosis after curative surgery for colorectal cancer: a systematic review. Ann Surg Oncol 20(1):183–192
EDITORIAL NOTES
Peritoneal Metastases: Prevention and Treatment Paul H. Sugarbaker 1
Received: 4 January 2016 / Accepted: 7 January 2016 / Published online: 4 February 2016 # Indian Association of Surgical Oncology 2016
Abstract Colorectal cancer is a surgicaly curable disease. It requires multimodality of treatment in Localy advanced and metastatic disease. Molecular markers like RAS mutation has brought in change in the mangement of metastatic disease. Nearly 15 to 20 % presents with peritonieal surface metastasis. The debate continues with systomic vs Cyutoreductive surgery with are without HIPEC. This article highlights management of peritoneal metastasis with special reference to prevention and treatment. Keywords Colorectal . Peritoneal surface . Cytoreductive . HIPEC
Open or laparoscopic surgery is an elegant and comprehensive treatment for a large majority (approximately 80 %) of patients who have a primary or colon or rectal cancer. Some * Paul H. Sugarbaker
1
Center for Gastrointestinal Malignancies, Program in Peritoneal Surface Oncology, MedStar Washington Hospital Center, Washington, DC, USA
colon cancer patients with positive lymph nodes show improved survival when adjuvant systemic chemotherapy is added to surgery [1]. Also, some selected rectal cancer patients will have decreased local control with preoperative radiation therapy plus surgery [2]. However, the mainstay for optimal treatment of a majority of patients with primary colon and rectal cancer is surgery alone. Both the patient and the surgeon expect a complete recovery and restoration of high quality of life following this approach. Unfortunately, a small percentage (estimated at 20 %) of patients will have a biologically aggressive colorectal cancer or a delay in diagnosis that causes peritoneal seeding to occur a some time in the natural history of the disease. Current standard of care demands that these patients be considered for an individualized treatment plan. A regimen of treatment that involves referral to the medical oncologist for systemic chemotherapy treatment as a definitive management plan does not meet the standard of care. Metastases may be diagnosed at two different time points in these colorectal cancer patients. First, they may be recognized prior to or at the time of the colorectal cancer resection, identified as SYNCHRONOUS peritoneal metastases. Alternatively, the peritoneal metastases may be diagnosed during follow-up, regarded as METACHRONOUS peritoneal metastases. The occurrence of peritoneal metastases with modern treatment algorithms is not, of necessity, a lethal clinical situation. An estimate of long-term survival in these two groups of patients with modern treatments is 30 % [3]. In the patients with synchronous diagnosis of peritoneal metastases some will have a small extent of abdominal or peritoneal spread so that the peritoneal metastases can be resected along with the primary malignancy. If that is possible all disease should be removed with the initial colorectal cancer resection. After a short course of systemic chemotherapy these patients must be considered for a second-look surgical exploration and cytoreductive surgery with perioperative
138
chemotherapy using hyperthermic intraperitoneal chemotherapy (HIPEC) [4]. If the synchronous disease is too extensive to be radically resected, then the surgical procedure for the primary colorectal cancer must be modified to allow for a comprehensive management plan. The surgery should be performed so minimal dissection and very limited opening of peritoneal incisions occurs. The peritoneum is the first line of defense against peritoneal dissemination [5]. Cancer cells implant approximately a hundred times more efficiently into a traumatized peritoneal surface as compared to an intact surface. Fibrin entrapment of cancer cells rendered unresectable at the time of a reoperative surgical procedure as a result of progression deep to the peritoneum must be avoided when dealing with extensive synchronous colorectal disease. When colorectal cancer patients are found to have disease recurrence diagnosed during follow-up, peritoneal metastases are frequent. Up to 50 % of patients with colorectal cancer recurrence will have peritoneal implants as part of the recurrent disease process. This is in contrast to only 8 % of patients with synchronous metastases. It is estimated that approximately 10 % of these patients will have isolated peritoneal metastases and become candidates for a potentially curative approach using cytoreductive surgery with HIPEC. Using current potentially curative treatment regimens, the estimate of long-term survival in this group of patients is 30 % [4]. There is a third group of patients that can be benefited by special treatments directed at the peritoneal surface component of colorectal cancer. These are patients at HIGH RISK for subsequent progression of peritoneal metastases. In these patients, peritoneal metastases cannot be documented at the time of primary colorectal cancer resection. However, these patients with serosal invasion of the primary cancer, positive margins of resection, and patients who have a perforation through the primary malignancy will develop peritoneal metastases greater than 50 % of the time [6]. Other gastrointestinal cancer patients have this high risk for subsequent peritoneal metastases. This includes gastric cancer patients with serosal invasion. Also, pancreas cancer patients resected for cure who have narrow or positive margins of resection are at high risk for local-regional recurrence with or without peritoneal metastases. Over 50 % of these gastric or pancreas cancer patients will manifest subsequent peritoneal metastases. These patients at high risk for subsequent peritoneal metastases are candidates for adjuvant treatment with HIPEC. In the past, these three groups of patients did not have special treatments designed to maximize their long-term survival. Systemic chemotherapy was used but improvement in disease-free survival was not frequent and a curative approach never materialized. In this special issue of the Indian Journal of Surgical Oncology these three groups of gastrointestinal cancer patients are the focus of the text. It critically evaluates the radiologic techniques that should be used to diagnose, anatomically locate,
Indian J Surg Oncol (June 2016) 7(2):137–138
and quantify peritoneal metastases. The role that laparoscopy can play to assist in patient selection is presented. The surgical treatments and special perioperative cancer chemotherapy for appendiceal, colorectal, and gastric cancer are thoroughly discussed by authors completely familiar with these treatments. Also, preoperative, intraoperative (anesthetic management), and postoperative management to maximize the safety of these advanced surgical procedures are included in this special issue. Patient selection for treatment must be a major focus in this new and important aspect of peritoneal surface oncology if high quality results are to be achieved. In summary, this special issue of the Indian Journal of Surgical Oncology presents to the cancer surgeon a new standard of care for selected patients. If we can select the appropriate patients and initiate safe and effective treatments, with current technology using cytoreductive surgery plus perioperative chemotherapy, large benefits will accrue. This approach to prevention and treatment of peritoneal metastases is a relatively new addition to the required surgical management strategies for gastrointestinal cancer. New concepts and treatment plans are being published on a weekly basis. Although current treatment plans are safe and effective and must be implemented at this point in time, new and improved approaches with added benefit are expected in the near future. A comprehensive approach to the prevention and treatment of peritoneal metastases presents a new frontier for progress in the management of gastrointestinal malignancy.
References 1.
Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG (2015) Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial. J Clin Oncol 33: 3733–3740 2. Fitzgerald TL, Brinkley J, Zervos EE (2011) Pushing the envelope beyond a centimeter in rectal cancer: Oncologic implications of a close, but negative margins. J Am Coll Surg 213:589–595 3. Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M, Barone R, Yonemura Y, Cavaliere F, Quenet F, Gutman M, Tentes AA, Lorimier G, Bernard JL, Bereder JM, Porcheron J, Gomez-Portilla A, Shen P, Deraco M, Rat P (2004) Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: A multi-institutional study. J Clin Oncol 22(16):3284–3292 4. Elias D, Goéré D, Di Pietrantonio D, Boige V, Malka D, KohnehShahri N, Dromain C, Ducreux M (2008) Results of systematic second-look surgery in patients at high risk of developing colorectal peritoneal carcinomatosis. Ann Surg 247(3):445–450 5. Sugarbaker PH (2007) Peritoneum as the first line of defense in carcinomatosis. J Surg Oncol 95(2):93–96 6. Honoré C, Goéré D, Souadka A, Dumont F, Elias D (2013) Definition of patients presenting a high risk of developing peritoneal carcinomatosis after curative surgery for colorectal cancer: a systematic review. Ann Surg Oncol 20(1):183–192
