Structured Follow-Up after Colorectal Cancer Resection: Overrated R. Taylor Ripley University of Colorado Grand Rounds April 23, 2007
Guidelines for Colonoscopy Production: Surveillance US Multi-Society Task Force on Colorectal Cancer American Cancer Society (ACS) Endorsements: Colorectal Cancer Advisory Committee of ACS American College of Gastroenterology - Governing Board American Gastroenterological Association Institute American Society for Gastrointestinal Endoscopy Douglas K. Rex, Gastroenterology 2006
Guidelines for Colonoscopy Eligible patients: Stage I Endoscopically resected Stage II and III Stage IV - Resected for cure with isolated hepatic or pulmonary metastasis. Surveillance Abeloff: Clinical Oncolgy
Guidelines for Colonoscopy Surveillance Perioperative clearance of synchronous neoplasia: Guidelines state: Clearance of colorectum performed near time of resection Non-obstructed colons: Colonoscopy Obstructed colons: Double contrast barium enema or Computed tomography colonography with Colonoscopy in 3 6 months.
Peri-operative Screening Gastrointestinal Radiology 2006
Guidelines for Colonoscopy Recommendations: Surveillance I. Colonoscopy 1 year II. Colonoscopy 3 years after 1 st III. Colonoscopy 5 years after 2 nd IV. Shorter Intervals: I. Patient s Age II. Family history III. Hereditary Non-Polyposis Colorectal Cancer V. Periodic examination of Rectum I. Consider 3 6 month: Endoscopic Ultrasound; rigid II. proctoscopy, flexible proctoscopy Independent of recommendations for colonoscopy
Recommendations? Overrated!
Overrated Basis of Recommendations Goals of Surveillance Specifics related to Rectal Cancer
Basis of Recommendations (Methods) Review of all English Literature for surveillance of malignant disease. 66 studies evaluated. Exclusion: 43 studies No perioperative clearance Non-Colonoscopy: Sigmoidoscopy or barium enemas Preliminary data for on-going trials
Basis of Recommendations 23 studies in analysis Randomized controlled trails Cohort studies Retrospective and Prospective trials Evidence tables Circulated to two committees responsible for recommendations Not published or available for review
Limitations
Limitations 1. Metachronous lesions: Variable definitions Site within colon vs. time of appearance 2. No mention of hereditary syndromes 3. Widely variable follow-up intervals Often incomplete 4. Metachronous lesions not always separated from anastomotic recurrences 5. Failures to report stage and resection for cure 6. Not clear: Asymptomatic surveillance vs. diagnostic procedure.
Limitations No statistical analysis of data Raw data only Guidelines state: Despite these limitations, number of clinically relevant trends are evident.
Overrated Basis of Recommendations Goals of Surveillance Specifics related to Rectal Cancer
Goals of Surveillance Two Fundamental Goals: 1. Detection of Early Recurrence of initial primary carcinoma. 2. Detection of Metachronous Colorectal Neoplasm
Detection of Early Recurrence of Initial Primary Carcinoma 325 pt randomized: Invasive vs. structured Invasive: Yearly colonoscopy Yearly CT scan liver CXR Clinical review Structured: Simple screening tests Clinical review Screening: CEA CBC, LFT s FOBT Clinical Review: History and Physical Schoemaker et al. Gastroenterology 1998
Detection of Early Recurrence of Standard: Initial Primary Carcinoma 154 colonoscopy 13 metachronous or recurrent lesions 5 detected by colonoscopy All investigated secondary to symptoms Intensive: 577 colonoscopy 10 metachronous or recurrent lesions 3 detected by colonoscopy 9/10 investigated secondary to symptoms Schoemaker Gastroenterology 1998
Detection of Early Recurrence of Initial Primary Carcinoma Conclusions: No significant difference in survival Yearly colonoscopy failed to detect any asymptomatic recurrences. One asymptomatic liver metastasis detected by CT scan One asymptomatic lung metastasis detected by CXR Yearly screening - Not improve Survival Schoemaker Gastroenterology 1998
Detection of Early Recurrence of Initial Primary Carcinoma British Medical Journal 2002: Meta-Analysis of all surveillance studies No survival benefit for yearly colonoscopy Failure to improve survival: Low rates of anastomotic or intraluminal recurrence Unresectable intra-abdominal or pelvic disease not influenced by screening.
Detection of Early Recurrence of Initial Primary Carcinoma Recommendations: Based on Guidelines Performance of annual colonoscopy for the purpose of detecting recurrent disease does not have an established survival benefit for patients with colorectal cancer.
Primary Goal? Not just Overrated Useless!
2 nd Goal: Detection of Metachronous Colorectal Neoplasm
Distinguish between Synchronous and Metachronous: Synchronous Primary Cancer: Prospective study 5 years 166 pt. colorectal CA Colonoscopy either Pre / Post Operative Langevin, Am J Surg 1984
Synchronous Cancer Finding Patients (%) Synchronous Cancer: 8 / 166 (5%) Benign Neoplastic Polyps: 46 / 166 (28%) Cancer Not in Specimen: 7 / 8 (88%) Polyp Not in Specimen: 31 / 46 (67%) Langevin Am j Surg 1984
Synchronous Colorectal CA Conclusion: Entire colon should be evaluated Other studies: 2 7% rate of synchronous cancer
Synchronous Cancer If synchronous colorectal cancer is not carefully ruled out, these tumors may erroneously be mistaken for metachronous neoplasia at a later date.
Synchronous vs. Metachronous Guidelines admit: Clear evidence that quality of examinations is highly variable. Admit that distinguishing between truly metachronous verses synchronous impossible with cited studies. Therefore: Conclusions drawn from this data inaccurate - Cannot ensure high quality examinations that excluded synchronous lesions from the data. Rex D, J Clin Gastroenterol 2005
Metachronous Lesion 23 studies: Apparent Metachronous Cancers: 137 / 9027 pts. = 1.5 % Number of colonoscopies not reported in 13 studies. 10 studies: 60 cancers / 9407 colonoscopies = 0.6% 1 / 157 cancer / colonoscopy. Guidelines for Surveillance based on above data Rex Gastroenterol 2006
Metachonous Metachonous Cancer: 69 / 106 (65%) Dukes A or B Reported numbers excluded Stages higher than Duke s A or B The groups more likely to have symptoms
Metachonous Symptomatic: 29 / 52 (56%) Asymptomatic 23 / 52 (44%) Symptomatic 85 pts. Unknown symptoms Truly asymptomatic patients: 29 / 9407 = 0.31 %
Metachronous Symptomatic patients: Guidelines: Surveillence guidelines are intended for asymptomatic people; new symptoms may need diagnostic work-up. Yet: Guidelines included symptomatic patients in data analysis.
Data does not adequately segregate patients into asymptomatic surveillence group the group who will receive the colonoscopies
Metachronous Mark Twain s three types of lies 1. Lies 2. Damn Lies 3. Statistics Conclusions for metachronous lesions Not based on this data.
Metachronous Prospective Cohort 611 pts Presented for followup Colonoscopy after resection Fecal occult blood test performed all pts. FOBT + : 59 pts (13.6%) 9 recurrent (4) / metachronous (5) cancer 12 adenomatous polyps 1 radiation proctitis 2 pan-colonic mucositis FOBT - : 552 pts (86.1%) No cancers 38 adenomatous polyps Skaife Colorectal Disease 2003
Metachronous Results: All metachronous cancer would have been detected by screening Symptoms and FOBT adequate indications for follow-up colonoscopy Yet this study concluded: Surveillance with colonoscopy is valuable. Wrong Conclusion
Metachronous Standard recommendations: Screen highrisk adults older than 50 every 5 years. Includes previous colorectal malignancy Neoplastic growth rate slow 5yr average for polyp to convert to neoplasia Most asymptomatic patients would be detected without intensive surveillance of the colon based on population screening.
Metachronous Colonoscopy for the 2 nd Goal: To detect metachronous disease Not valuable.
Therefore Synchronous Lesions: High Quality colonoscopy Essential Surveillance: Overrated in truly Asymptomatic Patients
Overrated Basis of Recommendations Goals of Surveillance Specifics related to Rectal Cancer
Rectal Cancer Surveillance Recommendation: Consider 3 6 month evaluation: Endoscopic Ultrasound; rigid proctoscopy, flexible proctoscopy Based on local recurrence: Historically >10%, not metachronous lesions No longer applicable because
Advances in Rectal Cancer Technique: Total Mesorectal Excision Sharp dissection of mesorectal facia Increased rates of successful low anterior resections (~7%) Neoadjuvant therapy: Radiotherapy 5 Gy 5 days Neoadjuvant Chemotherapy added to radiotherapy Kapiteijn NEJM 2001
Survival after Rectal Resection Kapiteijn NEJM 2001
Local Recurrence: 1748 patients Kapiteijn NEJM 2001
Rectal Cancer Surveillance: Based upon results of recurrence rates prior to widespread total mesorectal excision and pre-operative radiotherapy. Unlike Colon Cancer: Not based on metachronous lesions, but local recurrence Update: Advanced technique reduce need for surveillance. Local recurrence detection does not increase survival
Surveillance of Rectal Cancer? Also Overrated
Conclusion Guideline Basis: Symptomatic patients included Symptoms Surveillance Not mention hereditary syndrome Multiple locations common No statistical analysis
Conclusion Goals of Surveillance: 1 st goal: Anastomotic or recurrent disease Not improve survival secondary to nature of recurrence Not recommended by guidelines 2 nd goal: Metachronous lesion detection Most detection of lesions based upon symptoms Routine colonoscopy for high risk group will detect disease at standard 5 year interval
Conclusion Rectal Cancer Significant improvements in technique and neoadjuvant therapy Local recurrence usually symptomatic and usually represents pelvic disease Overall: Guidelines significantly over estimate the value of intensive colorectal surveillance after colorectal cancer resection.
Intensive Surveillance??? No Overrated.