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Chemoradiation vs Surgery for rectal cancer
- 1. Under what Circumstances would chemoradiation +/- LE be comparable to radical surgery? Christopher H. Crane, M.D. Program Director, GI SectionProgram Director, GI Section Department of Radiation OncologyDepartment of Radiation Oncology
- 3. GI Mucosa Limits the XRT Dose • Many other tumors: definitive doses possible – Lung, head and neck, prostate, liver, anal ca • Luminal GI tumors: esophageal, gastric, rectal – The tumor resides within a serial organ at risk – Limits the dose to 54Gy or so.
- 4. Complications of Radical Rectal Surgery • Permanently altered bowel function – Often colostomy • Urinary dysfunction from 7-68% • Impotence 15-100% • Retrograde ejaculation 3-35%
- 5. NCDB LE Special Study (1994-96) Local Recurrence – T2 5- Year LE RR T2 22% 15% T2: p=0.01 You et al. Ann Surg 245(5):726-33, 2007 N=164 N=866
- 6. German Trial (CAO / ARO / AIO) Pre-operative vs Postoperative CXRT • Significantly lower acute toxicity rate – 27% vs 40%, p=0.001 • LR improved with preoperative CXRT – 5 yr: 6% vs 13%, p=0.001 • SP higher in preoperative CXRT – 39% vs 19%, p=0.006 – Subjective need for APR, not whole group • Significantly lower late toxicity – 14% vs 24%, p=0.01 • anastamotic stricture (12% vs 4%) • Diarrhea, SBO (9% vs 15%) Sauer, R NEJM, 351, 2004
- 7. CXRT / Mesorectal resection- cT3 N0 pts ypN+ according to ypT stage Crane, pESTRO 2004 ypT0 in T3 NX (including clinically node +) = 4/45 = 9% Bedrosian, J Gastroint Surg, 2004 Pathologic T Stage Institution 1 Institution 2 Institution 3 Total ypT0 0/27 (0%) 0/14 (0%) 1/43 (2%) 1/84(1%) ypT1 2/29 (7%) 0/12 (0%) 4/17 (24%) 6/58 (10%) ypT2 15/95 (16%) 12/97 (12%) 4/60 (7%) 31/252 (12%) ypT3 54/166 (33%) 62/164 (38%) 15/68 (22%) 131/398 (33%) ypT4 0 5/5 (100%) 2/2 (100%) 7/7 (100%)
- 8. Can Radical Surgery Be Avoided in Selected Rectal Cancer Patients?
- 9. *Responding patients Chemoradiation Followed by Local Excision*
- 10. Local Excision of T3 tumors after Preoperative XRT Study # Patients % pCR/mRD % LF (5-yr act) Median FU Mohiuddin, TJU, 1994 15 Downstaged 0 40 Kim, USF, 2001 17 100/0 0 19 Bonnen, MDACC, 2004 26 54/35 6 51 Lezoche, Italy 2005 46 0/23 5 55 Meadows, UF, 2006 16 56/44 21 (3 yr) 9 (with salvage) 27
- 11. Local Excision of T2 tumors after Preoperative XRT Study # Patients % pCR % LF Median FU Lezoche, Italy 2005 54 16(30%) 5 (5 yr) 55 Meadows, UF, 2006 16 T1/T2 4(25%) 9 (3 yr) 27
- 12. ypT stage All patients -seven studies LR T0 0/53 (0%) T1 1/45 (2%) T2 6/85 (7%) T3 7/33 (21%) Total 17/237 (7%) Cumulative recurrence rates based on ypT Stage CXRT/LE (cT2/cT3) Modified from Table 5, Borschitz, et al Ann Surg Onc, 2008
- 13. Randomized Trial - T2 Rectal Cancer CXRT then TAE vs Laparoscopic Resection • 40 pts • 50.4 Gy + PVI 5-FU (200 mg/m2 ) – 20 TAE – 20 LAP Resection • One recurrence in each group (5%) • Median FU 56 mo Lezoche, et al Surgical Oncology, 2005
- 14. ACOSOG Z6041 Study Design uT2 rectal cancer (EUS- MRI) CXRT Cape (850mg/m2 bid) oxali (50 mg/m2/wk) 54 Gy Local excision T0-T2 R0: Observation T3 or R+: radical resection F o l l o w <8 cm from anal verge <4 cm size Primary Obj: 3 yr DFS in uT2N0 Chan, ASTRO 2010
- 15. ACOSOG Z6041 Study Design uT2 rectal cancer (EUS- MRI) CXRT Cape (650mg/m2 bid) oxali (50 mg/m2/wk) 50.4Gy Local excision T0-T2 R0: Observation T3 or R+: radical resection F o l l o w <8 cm from anal verge <4 cm size Primary Obj: 3 yr DFS in uT2N0 Chan, ASTRO 2010
- 16. Conclusions Neoadjuvant CRT with CAPOX • 44% pCR • Only 5% of patients needed radical surgery • Long term follow-up is needed for LC endpoint • High GI toxicity rates Chan, ASTRO 2010
- 17. Author Wound dehiscence Transient incontinence Kim et al 1/26 (4%) 1/26 (4%) Ruo et al 1/10 (10%) None Schell et al None 2/11 (18%) Hershman et al NS NS Bonnen et al NS NS Stipa et al None 1/26 (4%) Lezoche et al 11/100 (11%) 2/100 (2%) NS, not specified; nCRT, neoadjuvant chemoradiation; LE, local excision. Complications, CXRT / TAE Modified from Table 3, Borschitz, et al Ann Surg Onc, 2008 •Wound complications do not appear to be a limitation •Diverting iliostomy could be perfomed
- 18. Non-operative Management in Complete Responders? • University of São Paulo, Brazil • Pre-op Chemoradiation (50.4 Gy + FU/LV) • 265 pts – Clinical CR = observation (n=71, 26%) • 2 endorectal failures, 5y OS 100% – Incomplete CR / radical surgery, pCR (n=22%, 8.3%) • 2 DOD, 5y OS 88% • Median follow-up 57.3 months Habr-Gama, Ann Surg. 240(4):711-718, 2004
- 19. Organ Preservation Model Locally Advanced Rectal Ca • Clinical selection will affect success – Tumor size, nodal status, tumor grade, others • Neoadjuvant CXRT – Endoscopic CR • Full thickness local excision = excisional biopsy of tumor bed – ypT0, no further surgery • Radical surgery only for non-responders: – Gross residual disease or ypT3 • What about microscopic residual disease? Crane, Annals of Surg Onc, (3) p288-90, 2006
- 20. Response of Primary Tumor to CXRT • Observing response of primary key to organ preserving strategy • Predicts Control of Microscopic Mesorectal Disease • Could predicting response help? – Only if it leads to personalized therapy – Increase the pool of responders • Pair agents to patients – Proteomics, genomics • Change agents during therapy (PET)?
- 21. The Message Regarding Pre-op/LE • Promising strategy, especially in responding patients • Better long term GI and sexual function • Salvage rates of LR 50-70% – Close FU is critical • Multidisciplinary team has to be on the same page