Presentation on theme: "Rectal Cancer: A Complete Clinical Response…Now what? University of Virginia."— Presentation transcript:
Rectal Cancer: A Complete Clinical Response…Now what? University of Virginia
Objectives Outline a protocol at UVA for the non- operative management of patients with a complete clinical response following neoadjuvant chemoradiation for a locally advanced rectal cancer
Standard of Care (NCCN) Locally Advanced Mid/Low Rectal Cancer Neoadjuvant chemoradiation Radical surgery with a Total Mesorectal Excision (TME) Adjuvant chemotherapy
Total Mesorectal Excision after Chemoradiation Very good oncologic outcomes!!! BUT…..
Total Mesorectal Excision after Chemoradiation Mortality, in some series 2% Need for stoma –APR about 30% –Low anastomosis, temporary or permanent Sexual and bladder dysfunction Functional problems –Bowel function –Depression, body image Wound complications
Are we overtreating?
Pathological complete response!!! 8-24% Lancet 2010, Mass M.
5 Year Outcomes Complete response after radical surgery Local Recurrence pCR 2.8% No pCR 9.7% Distant metastasis free survival pCR 88.8% No pCR 74.9% Lancet 2010, Mass M.
5 Year Outcomes Complete response after radical surgery pCR 90% No pCR 77% pCR 2% No pCR 10% OncoTargets and Therapy 2013, Solanki A
Question For selected individuals with a complete clinical response can we forego radical surgery??
Annals of Surgery, October 2004
Protocol 265 patients, Tumors <= 7 cm from the anal verge 50.4 Gy 5-FU (425 mg/m2/d) and folinic acid (20 mg/m2/d) IV for 3 consecutive days on the first and last 3 days of radiation therapy. NO ADJUVANT CHEMOTHERAPY
Protocol Assessed at 8 weeks If complete response patients followed monthly If sustained over 12 months response they were enrolled and considered complete responders. 14 patients “recurred” in first year (16%) 71 enrolled (27% of group)
Incomplete response Radical Surgery
Local Recurrence 2/71 luminal recurrence –Both treated locally and no recurrence –No pelvic failures 0/22 pelvic recurrence
Systemic Recurrence 3/71 (4.2%) 3/22 (13.6%) Mean Follow up Observation 57.3 months (12-156) Resected 48 months (12-83)
Survival Data Observation vs Resected 5 yr Overall Survival Observation 100% Resected 88% 5 yr Disease Free Survival Observation 92% Resected 83%
Concerns Late recurrences with radiotherapy Single institution Determining clinical response Correlation between clinical response and pathological response
Reaction Made surgeons very uneasy Not ready for prime time Used when patients are elderly, frail or with metastatic disease But…..
JOURNAL OF CLINICAL ONCOLOGY 2011, Mass, M. Netherlands
YearCEADREEndoMRICT for distant mets 14x 2x 24x2x 1x 34x2x 1x 42x 1x 52x 1x Surveillance Program JOURNAL OF CLINICAL ONCOLOGY 2011, Mass, M.
Results Mean Follow up 25 months 1/21 developed endoluminal recurrence –Refused radical surgery and got a local excision and now disease free 20 disease free 2-year DFS is 89% OS is 100%. Comparable to control with ypT0N0M0 after radical surgery
Conclusions Similar overall survival Better functional outcomes Salvage surgery possible Very strict criteria, so some with a ypT0N0M0 still got surgery Adjuvant chemotherapy
NATUREREVIEWS|GASTROENTEROLOGY&HEPATOLOGY Minsky, 2013 Watch and Wait Strategy
Conclusions Highly selective non-operative therapy may be appropriate Salvage surgery possible
Can we increase the number of complete responders? Wait longer –Double complete response if you wait longer than 8 weeks More radiation Different chemotherapy regimens –Oxaliplatinum, Avastin –Different timing Adjuvant chemotherapy
Diseases of the Colon and Rectum, 2013
Inclusion Criteria Palpable tumors, no more than 7 cm from anal verge cT2-T4, cN0-N1, cM0 High resolution MRI or 3-D Endorectal ultrasound Chest/Abd/Pelvic CT scan
Treatment 54 Gy –45 Gy via 3-field approach –9-Gy boost to the primary tumor and perirectal tissue (54 Gy total). 3 cycles bolus 5-FU (450 mg/m2), 50 mg of leucovorin for 3 consecutive days every 3 weeks After radiation, patients received 3 additional cycles of chemotherapy every 3 weeks.
Inclusion criteria Assessed at 10 weeks Complete response based on physical exam, endoscopy and radiology (MRI or PET/CT scan) No adjuvant chemotherapy was given
Salvage Procedures Late Recurrences Late recurrences 10% Salvage surgery seems successful Low local recurrence Systemic recurrence thus far not as big an issue Follow up pretty good Continuing assessment critical to success!!!
Conclusions Extended Chemoradiation with 54 Gy Initial complete response 68%!! 17% failure in first 12 month 10% failure long term Salvage surgery likely 51% handled non-operatively!!
What are we doing Last several years offering non- operative therapy to those that have a complete response and: –1. Have metastatic disease –2. Too frail for surgery –3. Refuse surgery
What we would like to do Develop a UVA protocol for this patient population Inclusion criteria Follow up protocol Track outcomes
Neoadjuvant XRT 8 Week Assessment Complete Response Enroll Significant regression RE-Assess in 8 weeks Complete response? Yes – Enroll No - Radical Surgery Poor response Radical Surgery
Enroll Encourage adjuvant chemotherapy –Discretion of referring oncologist Follow up –Flexible Sigmoidoscopy and exam every 3 months –CEA every 3 months –Imaging every 6 months – Alternate MRI and PET CT scan –For how long??
Questions and Concerns Do we need minimal standards for neoadjuvant XRT? Recommend “boost” if don’t operate? Recommend or require adjuvant chemotherapy? Define complete clinical response or just surgeon discretion? Decide on imaging follow up How long do we follow?