Is there a role for surgery in metastatic colorectal cancer?

Alan E. Harzman, MD

Assistant Professor - Clinical

Yes.

Thank you for your time.

Outline

• Obstruction

• Overview of colorectal metastasis

• Solid organ metastasis

• Peritoneal metastasis

Obstruction

Obstruction

• 8-29% of CRC patients at initial presentation

• 77% left-sided, 23% right-sided

Interventions

• Low-residue diet and start chemotherapy or radiation

• Laser therapy to open lumen (for distal lesions)

• Fulguration• Stent• Diverting stoma• Resection +/- anastomosis

– But not above another lesion

Overview

Sites of Colorectal Metastasis• Peritoneum• Liver

– Portal circulation

• Lung• Ovary• Bone• Brain• Incisions• Spleen• Other

Sites of Possible Ectomies• Peritoneum• Liver• Lung• Ovary• Bone• Brain• Incisions• Spleen• Other

Basic Elements of a Good Metastasectomy

• Long disease-free interval

• Slow-growing disease

• Good functional status

• Good exit strategy– This is not like a war. We can’t raise health

like the government can raise taxes

Lung

as an example

Factors in Lung Resection

• Ideally, a solitary metastasis. Possibly multiple nodules in one lung, or a single nodule in each.

• Primary site is controlled

• No other evidence of metastasis

• Patient can tolerate resection

Survival After Lung Resection

• Operative mortality – 3%

• 3-year survival – 45-78%

• 5-year survival – consistently around 30%

Liver

Liver Metastasis

• 60% of the 150,000 new US cases of CRC yearly will eventually develop liver metastasis.

• 10% of those people will be candidates for curative-intent hepatic surgery

• 5-10 month survival untreated

• 24-23% 3-year and 2-8% 5-year survival of people who might have been surgical candidates in retrospect

Surgical Options for Hepatic Metastasis

• Hepatectomy

• Hepatic Artery Infusion

• Radio frequency ablation

• Cryoablation

Hepatectomy

• Mortality – 5% or less

• Morbidity – 20-50%

• 5-year survival – 25-40%

• 10-year survival – 20-26%

• Median survival 24-46 months

Hepatectomy

• Not for– Extra-hepatic disease

• Except maybe pulmonary or anastomotic

– Incomplete resectability

• Two-thirds will recur

Peritoneum

aka peritoneal carcinomatosis

'Omental cake' in a patient with peritoneal carcinomatosis arising from appendiceal cancer.Glockzin et al. World Journal of Surgical Oncology 2009 7:5   doi:10.1186/1477-7819-7-5

Peritoneal Carcinomatosis - Mechanisms

• Seeding from T4 CRC

• Extravasation with perforation of the tumor

• Tumor perforation at operation

• Leakage of tumor cells from lymphatics or veins at time of operation

Peritoneal Carcinomatosis

• 10-15% of patients at CRC presentation

• 25-35% of CRC recurrences

• Survival 6-8 months without therapy

• Can lead to malignant ascites or malignant bowel obstruction

Peritoneal Surface Malignancy Group

• Increased probability of complete macroscopic cytoreduction in CRC– ECOG performance status <=2– No extra-abdominal disease– Up to three, small, resectable hepatic mets– No biliary obstruction– No ureteral obstruction– Small bowel – no gross mesenteric disease – Small-volume disease in gastro-hepatic ligament

(Cotte et al., 2009)

Pseudomyxoma Peritonei

• Often diagnosed with acute appendicitis, abdominal swelling or ovarian mass

• Minimal operating should be done at the time of diagnosis

• Confusing pathology

Factors in Pseudomyxoma Peritonei

• Tumor grade

• Extent of mesenteric invasion

• Liver metastasis

• Age

Cytoreductive Surgery

• Peritonectomy (parietal and visceral)• Greater omentectomy• Lesser omentectomy• Splenectomy• Cholecystectomy• Liver capsule resection• Small bowel resection• Large bowel/rectal resection• Hysterectomy• Oopherectomy• Cystectomy• Omphalectomy – for invasion of umbilicus

Omphalectomy in a patient with umbilical tumor infiltration.Glockzin et al. World Journal of Surgical Oncology 2009 7:5   doi:10.1186/1477-7819-7-5

(Cotte et al., 2009)

(Cotte et al., 2009)

Intraperitoneal Chemotherapy

• Mortality – 5%• Morbidity – 35%• Various agents, especially mitomycin C• Hyperthermia

– Increased chemotherapeutic activity– Direct effects – protein denaturation, induction of

apoptosis, inhibition of angiogenesis

• High local dose with less systemic toxicity• Complete gross resection is most important

– 5-year survival – 27-54%

Schematic diagram of HIPEC procedure.Glockzin et al. World Journal of Surgical Oncology 2009 7:5   doi:10.1186/1477-7819-7-5

Cytoreductive Surgery and IPHP

• Morbidity 25-41%– Surgical – Anastomotic leak, ileus, wound

infection, bleeding, thrombosis, embolism– Chemotherapeutic – Leukopenia, anemia,

thrombopenia, heart, liver, renal

• Mortality 0-8%

• Shows individual and institutional learning curves

Survival

• With cytoreductive surgery and intraperitoneal hyperthermic chemotherapy– Survival 15-32 months– 28-60 months with complete macroscopic

cytoreduction

• With systemic chemotherapy alone (5-FU/leucovorin)– 12-14 months

Quality of Life

• Acceptable functional status returns at 3-6 months

• 32% depressed at surgery, and 24% one year afterward

• Role and social functioning may remain impaired in long-term functioning

Summary• There are a wide variety of options for surgical

therapy in metastatic colorectal cancer. • Most are very invasive and somewhat risky. • However, they all extend meaningful life in

properly selected patients. • Those patients may be the minority of patients

with metastatic colorectal cancer, but with 150,000 new cases a year, there are many of them out there.

References• Berri, RN, & Abdalla EK. (2009). Curable metastatic colorectal cancer:

recommended paradigms. Current Oncology Reports, 11, 200-208. • Cotte, E, Passot, G, Mohamed, F, Vaudoyer, D, & Glehen, O. (2009).

Management of peritoneal carcinomatosis from colorectal cancer. The Cancer Journal, 15(3), 243-248.

• Glockzin, G. (2009). Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World Journal of Surgical Oncology, 7(5).

• Gordon, PH, & Nivatvongs, S. (2007). Principles and practice of surgery for the colon, rectum, and anus. Third edition. New York: Informa Healthcare.

• Moran, B, Baratti, D, Yan, TD, Kusamura, S, & Deraco, M. (2008). Consensus statement on teh loco-regional treatment of appendiceal mucinous neoplasms with peritoneal dissemination (pseudomyxoma peritonei). Journal of Surgical Oncology, 98, 277-282.

• Wolff, BG, Fleshman, JW, Beck, DE, Pemberton, JH, & Wexner, SD. (2007). The ASCRS textbook of colon and rectal surgery. New York: Springer.