Presentation on theme: "Rectal Cancer: A Complete Clinical Response…Now what?"— Presentation transcript:
1 Rectal Cancer: A Complete Clinical Response…Now what? University of Virginia
2 ObjectivesOutline 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
3 Standard of Care (NCCN) Locally Advanced Mid/Low Rectal Cancer Neoadjuvant chemoradiationRadical surgery with a Total Mesorectal Excision (TME)Adjuvant chemotherapy
4 Total Mesorectal Excision after Chemoradiation Very good oncologic outcomes!!!BUT…..
5 Total Mesorectal Excision after Chemoradiation Mortality, in some series 2%Need for stomaAPR about 30%Low anastomosis, temporary or permanentSexual and bladder dysfunctionFunctional problemsBowel functionDepression, body imageWound complications
8 Pathological complete response!!! 8-24%Lancet 2010, Mass M.
9 5 Year Outcomes Complete response after radical surgery Local RecurrencepCR 2.8%No pCR 9.7%Distant metastasis free survivalpCR 88.8%No pCR 74.9%5-year risk for local recurrence was 2·8% (95% CI 1·6–5·1) in the pCR group (12/455 patients had local recurrences) and 9·7% (8·4–11·2) in the no pCR group (202/2478; unadjusted HR 0·33, 95% CI 0·19–0·60; p<0·0001). 5-year distant- metastasis-free survival was 88·8% (84·8–91·8) for patients with pCR (38/419 had distant metastasis) and 74·9% (72·9–77·0) for patients without pCR (512/2257; unadjusted HR 0·40, 0·29–0·55; p<0·0001). 5-year overall survival was 87·6% (83·6–90·7) for patients with pCR (53 deaths in 465 patients) and 76·4% (74·4–78·3) for those without pCR (614 deaths in 2538 patients; unadjusted HR 0·51, 0·38–0·67; p<0·0001).Lancet 2010, Mass M.
10 5 Year Outcomes Complete response after radical surgery pCR 2%No pCR 10%pCR 90%No pCR 77%OncoTargets and Therapy 2013, Solanki A
11 QuestionFor selected individuals with a complete clinical response can we forego radical surgery??
13 Protocol 265 patients, 1991-2002 Tumors <= 7 cm from the anal verge 50.4 Gy5-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
14 Protocol Assessed at 8 weeks If complete response patients followed monthlyIf sustained over 12 months response they were enrolled and considered complete responders.14 patients “recurred” in first year (16%)71 enrolled (27% of group)
22 JOURNAL OF CLINICAL ONCOLOGY 2011, Mass, M. Netherlands
23 Surveillance Program Year CEA DRE Endo MRI CT for distant mets 1 4x 2x 345JOURNAL OF CLINICAL ONCOLOGY 2011, Mass, M.
24 Results Mean Follow up 25 months 1/21 developed endoluminal recurrenceRefused radical surgery and got a local excision and now disease free20 disease free2-year DFS is 89% OS is 100%.Comparable to control with ypT0N0M0 after radical surgery
25 Conclusions Similar overall survival Better functional outcomes Salvage surgery possibleVery strict criteria, so some with a ypT0N0M0 still got surgeryAdjuvant chemotherapy
26 Watch and Wait Strategy Dalton: 50% recurred in first year. All salvaged by surgery. 2 developed mets though. But same as controlNATUREREVIEWS|GASTROENTEROLOGY&HEPATOLOGYMinsky, 2013
27 Conclusions Highly selective non-operative therapy may be appropriate Salvage surgery possible
28 Can we increase the number of complete responders? Wait longerDouble complete response if you wait longer than 8 weeksMore radiationDifferent chemotherapy regimensOxaliplatinum, AvastinDifferent timingAdjuvant chemotherapy
30 Inclusion CriteriaPalpable tumors, no more than 7 cm from anal vergecT2-T4, cN0-N1, cM0High resolution MRI or 3-D Endorectal ultrasoundChest/Abd/Pelvic CT scan
31 Treatment54 Gy45 Gy via 3-field approach9-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 weeksAfter radiation, patients received 3 additional cycles of chemotherapy every 3 weeks.
32 No adjuvant chemotherapy Inclusion criteriaAssessed at 10 weeksComplete response based on physical exam, endoscopy and radiology (MRI or PET/CT scan)No adjuvant chemotherapywas given
39 Salvage Procedures Late Recurrences Salvage surgery seems successfulLow local recurrenceSystemic recurrence thus far not as big an issueFollow up pretty goodContinuing assessmentcritical to success!!!
40 Conclusions Extended Chemoradiation with 54 Gy Initial complete response 68%!!17% failure in first 12 month10% failure long termSalvage surgery likely51% handled non-operatively!!
41 What are we doingLast several years offering non-operative therapy to those that have a complete response and:1. Have metastatic disease2. Too frail for surgery3. Refuse surgery
42 What we would like to doDevelop a UVA protocol for this patient populationInclusion criteriaFollow up protocolTrack outcomes
43 Significant regression Neoadjuvant XRT8 Week AssessmentComplete ResponseEnrollSignificant regressionRE-Assess in 8 weeksComplete response?Yes – EnrollNo - Radical SurgeryPoor responseRadical Surgery
44 Enroll Encourage adjuvant chemotherapy Follow up Discretion of referring oncologistFollow upFlexible Sigmoidoscopy and exam every 3 monthsCEA every 3 monthsImaging every 6 months – Alternate MRI and PET CT scanFor how long??
46 Questions and Concerns Do we need minimal standards for neoadjuvant XRT?Recommend or require adjuvant chemotherapy?Define complete clinical response or just surgeon discretion?Recommend “boost” if don’t operate?Decide on imaging follow upHow long do we follow?