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Surgical Approach to Cancer Care
- 1. ©2017 MFMER | slide-1 Rapid Integration Training Surgical Colorectal Cancer Care Amit Merchea, MD, FACS, FASCRS Division of Colon & Rectal Surgery Mayo Clinic in Florida Assistant Professor of Surgery, Mayo Clinic College of Medicine @merchea_md
- 2. ©2017 MFMER | slide-2 Disclosures • No relevant financial disclosures.
- 3. ©2017 MFMER | slide-3 Objectives • Role of surgery in colon and rectal cancer • Role multidisciplinary integration with surgery • Standards for staging, neoadjuvant treatment, genetic testing/lynch syndrome • Impact of perioperative period on oncology care
- 4. ©2017 MFMER | slide-4 Background • >90,000 new cases diagnosed yearly • 3rd most common cause of cancer death • Most present with localized disease • ~20% with metastatic disease • Surgery is the mainstay of treatment • Segmental, TAC, TPC • LAR • APR • CAA • TAE
- 5. ©2017 MFMER | slide-5 Staging • CT Chest, Abdomen, Pelvis • Liver MRI if suspicious, but not definitive CT findings • MRI with Eovist • CEA • Limited utility of PET • Variable practice… often incomplete
- 6. ©2017 MFMER | slide-6 • Compare staging between GI and non-GI physicians • 277 patients; 141 ordering physicians (68 GI, 73 non-GI) • Colorectal Surgeon managed staging in 29% • GI physicians were more likely to omit CT chest in staging (65 vs. 47%) • Academic > Community Practice (50 vs. 21%)
- 7. ©2017 MFMER | slide-7 • Incidence of pulmonary metastases • 10-20% in rectal cancer • 5-10% in colon cancer • Unresected poor survival • Resected and R0 30-50% 5yr survival “Efforts to standardize initial staging practices by promoting guideline-based practice might limit additional radiographic study visits in the completion of CRC staging.”
- 8. ©2017 MFMER | slide-8 PET Scanning • Adjunctive Imaging Modality • Localization of recurrence in those with rising CEA, non-diagnostic conventional imaging • Clarification of equivocal findings • Change in management - 5-20% of patients • Being used as an adjunctive modality • ie. detection of extra-hepatic disease in those with hepatic metastases
- 9. ©2017 MFMER | slide-9 • 30 studies • 2/30 - primary CRC • Recurrent - Sn 91%, Sp 91% • Metastatic - Sn 91%, Sp 76% • Poor quality studies overall, bias • Economic modeling
- 10. ©2017 MFMER | slide-10 • 30 studies • 2/30 - primary CRC • Recurrent - Sn 91%, Sp 91% • Metastatic - Sn 91%, Sp 76% • Poor quality studies overall, bias • Economic modeling “…insufficient evidence to support routine use… in primary CRC… data are divergent and the quality of research is poor… potentially cost effective in recurrent and metastatic disease, but not in primary…”
- 11. ©2017 MFMER | slide-11 • Adult patients with CRC treated by surgery and with hepatic metastases • Randomized 2:1 PET/CT and control • Primary outcome was change in hepatic surgery or extra-hepatic surgery; Secondary outcome was survival • 21/263 (8%) had a change in surgical management • 8/21 did not have any resection • Liver resection was performed in 91% PET group, 92% control group JAMA. 2014 May 14;311(18):1863-9. doi: 10.1001/jama.2014.3740.
- 12. ©2017 MFMER | slide-12JAMA. 2014 May 14;311(18):1863-9. doi: 10.1001/jama.2014.3740. “Among patients with potentially resectable hepatic metastases… PET-CT compared with CT alone did not result in frequent change in surgical management. These findings raise questions about the value of PET-CT scans in this setting”
- 13. ©2017 MFMER | slide-13 Rectal Cancer – Locoregional Staging • MRI • T2 or greater • Obstructing/Bulky tumors • Nodal staging • Sn 66%, Sp 76% • Circumferential Radial Margin • ERUS • T1 vs. T2 • Accuracy in T4 ~ 50% • Nodal staging • Sn 67%, Sp 78% • Can biopsy nodes
- 14. ©2017 MFMER | slide-14 MERCURY Study Group • Aim: Assess surgical CRM, assess accuracy of MRI for staging • 408 consecutive patients • 87% had a clear CRM • Complete surgical specimen in 80% • MRI predicted clear margin - 349 patients • Clear on pathology in 327 (94%)
- 15. ©2017 MFMER | slide-15 Circumferential Radial Margin • Positive CRM = Increased LR, Decreased OS • “Threatened” CRM • Minimum - 2mm • Considered positive if <=1mm MERCURY Study Group, BMJ 2006.
- 16. ©2017 MFMER | slide-16 Neoadjuvant Treatment
- 17. ©2017 MFMER | slide-17 When and how? • Metastatic colon cancer • Stage II or III rectal cancer • Stage IV rectal cancer
- 18. ©2017 MFMER | slide-18 Lynch Syndrome
- 19. ©2017 MFMER | slide-19 Environmental 70% (Sporadic) Somatic mutations that occur over many years Older patients Genetic Colorectal Cancer 20 - 30% (Familial) Multifactorial inheritance Middle age patients 3 - 5% (Hereditary) Inherited highly penetrant mutations Younger patients
- 20. ©2017 MFMER | slide-20 Lynch Syndrome – Malignancy Spectrum Malignancy Lifetime Risk (%) Colon/Metachronous Endometrial Gastric HPB Ovarian Urinary Tract Rectum Small bowel, Brain, Skin Breast, prostate 75 / 30 30 – 60 20 15 15 10 1/year 1-3 ?
- 21. ©2017 MFMER | slide-21 V600 BRAF mutation MMR gene germline mutation Tumorigenesis (Colorectal) Microsatellite Instability hMLH1 gene somatic mutation hypermethylation Lynch Syndrome Sporadic CRC Imai K , Yamamoto H Carcinogenesis 2007;29:673-680 MLH1* MSH2 MSH6 PMS2
- 22. ©2017 MFMER | slide-22 Key Questions • Who should get tested? • How does Lynch Syndrome impact surgical decision making? • How is surveillance impacted?
- 23. ©2017 MFMER | slide-23 In patients with CRC, who should get molecular testing? • In the past: • Amsterdam I, II • Bethesda criteria • Currently: • It’s all over the place • No testing to testing everyone • NCCN recommendations • Patients ≤ 70 years Miss 40%
- 24. ©2017 MFMER | slide-24 • Compliance with guidelines are poor • Beamer et al. JCO 2012: • 139 centers (39 NCI-CC centers) • 42% report “reflex” MSI/IHC testing on either all pts or directed by risk factor • Barriers: Informed consent, who should be tested, interpretation of these tests Kastrinos F, Syngal S. JCO 2012;30:1024-1027
- 25. ©2017 MFMER | slide-25 Testing Algorithm Tumor BRAF / MLH1 promoter hypermethylation Hypermethylated & BRAF mutation No S Tumor IHC testing Normal all 4 MMR products Unlikely LS Normal surveillance Loss of MSH2, MSH6 or isolated PMS2 LS strongly suggested Offer germ-line testing Abnormal expression Loss of MLH1 / PMS2 complex Not LS Offer germ-line testing for MLH1 S – Surgical recommendations S S S
- 26. ©2017 MFMER | slide-26 What are the surgical considerations in a patient with CRC and confirmed Lynch? • Treating the primary tumor and… • Discussing the role of extended resection (metachronous lesions) Segmental vs. total colectomy Proctectomy vs. proctocolectomy • Impact on morbidity, QOL of more extensive surgical procedures
- 27. ©2017 MFMER | slide-27 Metachronous CRC Risk For MMR Gene Mutation Carriers: Advantage of More Extensive Surgery? • Risk of metachronous colorectal CA in segmental or extended colectomy • Patients – 382 MMR mutation carriers • Segmental (n=332), extensive (n=50) • Mean follow-up was 8 years Parry et al. Gut 2011;60:950-957
- 28. ©2017 MFMER | slide-28 Results - Metachronous CRC Risk Metachronous CRC* Extended 0/50 Segmental 74/332 (22%) Cumulative risk of CRC 16% at 10 years 41% at 20 years 62% at 30 years *Surveillance endoscopy in 78% every 16 mos So, YES! Parry et al. Gut 2011;60:950-957
- 29. ©2017 MFMER | slide-29 Despite close surveillance following colectomy, the risk of metachronous lesions in the remaining colon and rectum is high…. So, should we just do extended resections on all Lynch patients with a colon cancer?
- 30. ©2017 MFMER | slide-30 Risks vs. Benefits Discussion
- 31. ©2017 MFMER | slide-31 Segmental vs. Extended Colectomy Measurable Differences in Morbidity, Function and Quality of Life Operation Median Stool Complications QOL Frequency Segmental 2 25% 98.5% (n=321) Ileosigmoid 4 57% 94.9% (n=91) Ileorectal 5 40% 91.2% (n=110) You et al. DCR 2010;51:1036
- 32. ©2017 MFMER | slide-32 Who is at highest risk for interval colorectal cancers in Lynch syndrome? • MLH1 and MSH2 mutation carriers • Age between 40 and 60 years old • Strategy: • More intense surveillance (q1 year) • High-quality endoscopy (NBI, Chromoendoscopy) • Consider total colectomy Haanstra JF et al. Int J Colorectal Dis 2013
- 33. ©2017 MFMER | slide-33 Surveillance for Confirmed LS • Colon: annual colonoscopy, beginning at age 20-25 years • Ovaries: consideration of preventative salpingo-oophorectomy at age 35 years or after child-bearing • Endometrium: consideration of preventative hysterectomy at age 35 years or after child-bearing • Urinary tract: annual urine cytology, beginning at age 25-30 years • Gastrointestinal other than colon: consider upper endoscopy every 3-5 years at age 30-35 years • Physical and neurological examination annually beginning at age 25- 30 years
- 34. ©2017 MFMER | slide-34 Perioperative Period and Oncologic Care
- 35. ©2017 MFMER | slide-35
- 36. ©2017 MFMER | slide-36 Amit Merchea, MD, FACS, FASCRS Colon & Rectal Surgery twitter: @merchea_md
Editor's Notes
- 1. The role of surgery in colon and rectal cancer – briefly the types of operations, standards of care. 2. The role of oncology and multidisciplinary integration with surgery – Standards for neoadjuvant therapy for rectal cancer in particular, genetic testing/lynch syndrome 3. Impact on perioperative period of oncology care – timing of surgery, post-operative concerns, etc.
- Staging for CRC as recommended by numerous societies and NCCN consists of… In current practice, liver MRI is generally reserved for patients who have suspicious but not definitive findings on CT scan, particularly if better definition of hepatic disease burden is needed in order to make decisions about potential hepatic resection.
- Objective: To evaluate radiographic staging practices for newly diagnosed CRC between gastroenterologists versus non-gastroenterologists
- Incidence of pulmonary mets 10-20% in rectal, 5-10% in colon ca; unresected survival is very poor; resected and R0, 30-50% 5yr long term survival
- primary outcome was a change in surgical management defined as canceled hepatic surgery, more extensive hepatic surgery, or additional organ surgery based on the PET-CT. Survival was a secondary outcome. Specifically, 7 patients (2.7%) did not undergo laparotomy, 4 (1.5%) had more extensive hepatic surgery, 9 (3.4%) had additional organ surgery (8 of whom had hepatic resection), and the abdominal cavity was opened in 1 patient but hepatic surgery was not performed and the cavity was closed.
- MRI has other imaging factors that end up making it more accurate for LN staging CRM is better defined in MRI
- Magnetic Resonance Imaging in Rectal Cancer European Equivalence Study
- So… what exactly is the CRM… The plane of the mesorectal fascia seen on MRI correlates with the fascia propria of the mesorectum resected with TME. Involvement of the mesolectal fascia increases rate of LR 4-fold
- We know that colorectal cancer is a result of both environmental and genetic factors. Most patients with CRC (70%) develop sporadic cancers as a result of somatic mutations over a several year time period and present at an older age. 20 – 30% of patients getting CRC are those who have a family history and are predisposed based on multifactorial inheritance, they may be middle age patients and the smallest group of CRC patients we see are those with hereditary CRC due to highly penetrant mutations and they tend to be younger patients.
- Anyone taking care of LS patients must be familiar with the spectrum of disease and specifically for our discussion of patients already with CRC, the risk of metachronous CRC, and in females the high risk of endometrial cancer.
- We know that microsatellite instability at the molecular level leads to a variety of types of tumors including CRC. In patients with CRC there are 2 pathways in which we get microsatellite instability. One is a result of germline mutations in MMR genes, this is what we know as LS. The other pathway is a somatic mutation of one of the MMR genes MLH1 due to hypermethylation and this phenomena is seen in some sporadic cancers. We also know that pts who have this somatic MLH1 mutation will also have V600 point mutation in the BRAF gene and it is the combination of these hypermethylation and BRAF mutation, both of which can be tested for, that help differential LS from sporadic cancers that are a result of microsatellite instability.
- As I have stated, it is important to try and confirm LS in pts with CRC before they go to surgery. So, how do we decide which patients with CRC should undergo molecular testing? In the past, guidelines stipulated that anyone who met Amsterdam criteria should get tested or the Bethesda criteria. Now, it is all over the place some don’t test anyone, some test all patients with CRC. There are some new models that may increase the yield of testing by using a calculator tool, but this relies heavily on known family history. Developing colorectal cancer younger than age 50 Developing colorectal cancer and other cancers* linked with Lynch syndrome separately or at the same time Developing colorectal cancer with tumor features linked to Lynch syndrome at an age younger than 60 Colorectal cancer in one or more first-degree relatives who also has or has had another Lynch syndrome-related cancer*, with one of these cancers developing before age 50 Colorectal cancer in two or more first- or second-degree relatives with another Lynch syndrome-related cancer. *(colorectal cancer, endometrial cancer, small bowel, ureter, or renal pelvis cancer; some people would also consider including ovarian cancer)
- So, we hear a lot these days about standardized approaches and compliance with current guidelines. In this paper published in JCO a couple of years ago, the authors discussed the concerns that compliance was poor when it comes to management of patients with LS. They quote several studies but one specific one looked at the rate of testing for LS at 139 centers across the country and found less than half do testing for LS, either directed or universal testing. Barriers noted in the article were….
- So, what are the surgical considerations in patients with CRC and confirmed LS? Not only treatment of the primary tumor but also discussing the role of extended ….and the impact of theses extended resections on morbidity and QOL
- The next set of slides summarize the more recent literature that I believe provide an evidence based approach to patients with LS and can be useful in your discussions with LS patients. In this study by Susan Parry and her colleagues, published in Gut a couple of years ago, data was pooled from multiple centers to try assess the risk of developing a metachronous colon cancer following segmental colectomy and if there was an advantage to more extensive surgery (total colectomy)? They reviewed the records of 382 confirmed LS patients, 332 had a segmental…..
- What they found was that none of the patients in FU who had an extended colectomy developed a metachronous CRC compared to 22% in the group that underwent a segmental colectomy, despite the fact that almost 80% of patients had undergone surveillance endoscopy every 1-2 years. Using a statistical model, they estimated the cummulative risk of CRC after segmental resection to be as high a 62% at 30 years. So the answer is YES, there is an advantage to more extended colectomy.
- So, the data suggests, despite close surveillance….
- The discussion of whether or not to do a limited (segmental) versus more extended (subtotal) resection involves a discussion of the risks and benefits of each approach…and we all know that more extensive colectomy does not come without a price…
- Patients are very concerned with the impact of more extended colectomy on surgical risk, function and QOL. The data I use to counsel my patients on comes from a study published 4 years ago in DCR by one of our trainees at the time, Nancy You. They looked at the differences stool frequency, surgical complications and QOL in patients undergoing segmental vs. subtotal vs. total colectomy. They found that with more extensive colectomies, stool frequency increased, complications were higher, and QOL decreased.
- More data is emerging regarding who might be at the highest risk of developing an interval cancer after segmental colectomy. Patients with MLH1 and MSH2 defects, especially if history of previous CRC and between age 40 – 60 yrs old. Strategy in these patients might include…….