Rectal Cancer : Curative treatment without surgery

Transcription

1 Rectal Cancer : Curative treatment without surgery Dieter Hahnloser dieter.hahnloser@chuv.ch CHUV University Hospital Lausanne Switzerland

2 Reasons for intervention (surgery) Cure Live longer Feel better

3 CRM (Circumferential Resection Margin) Local recurrence Birbeck KF. Ann Surg 2002

4 CRM predicts outcome LR Mets 5yrsSV CRM pos 22% 40% 40% CRM neg 5% 12% 80% Wibe A. BJS 2002 LR overall SV CRM pos 23.7% 44.5% CRM neg 8.9% 66.7% Bernstein BJS 2009

5 Predicting CRM CT MRI

6 Predicting CRM CRM 4 mm CRM 10 mm

7 Radiotherapy influences CRM Bujko K. BJS pts, TME follow-up: 4 yrs 5x5 GY 50.4Gy +5-FU CRM pos 12.9% 4.4% pcr 0.7% 16% Sphincter- Preservation 61.2% 58.0%

8 CRM >1mm is ok Local Recurrence CRM 0-1mm CRM >1mm NCCTG 25% 3% Bernick P. Surg Oncl Clin N Amer 2000 CLASSIC 23% 9% Quirke P. LJ Pathol 2005

9 CRM = Pathology

10 CRM is most important! If CRM not compromised: Surgery! If ut1: Local excision possible

11 Single Port Transanal Surgery SPTS

12 Single Port Transanal Surgery SPTS

13 Single Port Transanal Surgery USZ/CHUV, Italy, Spain n=75 100% succesfull 8% fragmentation (all benign lesions) 8mm safety margins, all R0 Hopsital stay 3.4 days (1-21) SPTS 20% complications (14/15 patients grade I and II, one reoperation) Vaizey incontinence score 1 (1-4) at 310days (15-884) follow-up Hahnloser D. (submitted)

14 Recurrence-free survival N=224 TEM, 20 centres UK + Belgium Bach SP. BJS 2009

15 T1 rectal cancer: N+? Low risk High risk 4-7% 24-75% Using St Marks LN Positivity Model Tytherleigh MG/ Mortensen NJM. BJS 2008

16 T1Nx high risk T2Nx and now?

17 Immediate Radical Resection after Local Excision : a compromise? 100% 90% 80% 70% p=0.9 p=0.3 60% 50% 40% 30% 20% 10% T1N0-1 Cases (n=37) Primary radical surgery control (n=78) Local excision only control (n=77) Hahnloser D. DCR month after surgery

18 TME (Total Mesorectal Excision)

19 TME (Total Mesorectal Excision)

20 TME (Total Mesorectal Excision)

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22 COLOR II Short Term Oncologic Endpoints Lap Open P CRM 1.3 cm 1.3 cm 0.16 Distal margin 3.6 cm 3.6 cm 0.68 Lymph Nodes CRM < 2mm 9% 10% 0.78 Upper 10% 9% 0.92 Middle 9% 3% Lower 9% 21% van der Pas. Lancet Oncol 2013.

23 Platform for Teaching

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26 Séreuse en jaune au niveau de la face antérieure Face antérieure en noir Face postérieure, en vert

27 muqueuse Séreuse (encré en jaune)

28 Can oncologic outcomes be improved with robotic surgery? Improvement in quality of mesorectal specimen (scored by pathologist with no clinical information) Baik SH et al, ASO 2009; 16:1480-7

29 Surgery for Rectal cancer 2013 If CRM not compromised: Surgery! If ut1: Local excision possible If ut2-3: TME Risk factors: T3b (>5mm EMD), extramural venous invasion T3b vs. T3a regardless N(!): 26% vs. 10% LR Merkel S. Int J colorectal Dis % vs. 85% DFS

30 Surgery for Rectal cancer 2013 If CRM not compromised: Surgery! If ut1: Local excision possible If ut2-3: TME (if T3a, V0)

31 Surgery for Rectal cancer 2013 If CRM not compromised: Surgery! If CRM compromised: CRT

32 German Trial German Rectal Cancer Study Group 11yrs Folow-up J Clin Oncol 2012

33 15-30% no residual disease Complete Pathological Response To Neoadjuvant Chemoradiotherapy Study n= Interval to surgery cpr rate (weeks) EORTC % EXPERT % CORE % RTOG % ypt0 ypn0 M0

34 Is histological response really a trustworthy surrogate marker for survival of the patient, or is it just a nice finding for surgeons and pathologists? «.it is a pcr, what a great job, we got it all out!»

35 pcr Local recurrence 0.7% Distant failure 8.7% 5yrs SV 90.2% DFS 87.0% 26 month median Adj chemo? 16 studies, n=3363 patients (1263 with pcr = 24.4% and 2100 without), FU 55.5 (40 87) months Martin ST. BJS 2012

36 Implications of pcr How to increase pcr? Less radical surgery? (organ sparing surgery) «Watch and wait»?

37 Aguilar JG. Ann Surg FU mfolfox-6 6 weeks 18% pcr 11 weeks 25% pcr same R0 rate, sphincter preservation, CRT toxicity increased fibrosis but same morbidity of surgery

38 Wolthuis AM. Ann Surg Oncol weeks 16% pcr >7 weeks 21% pcr N=356 stage II and III mid and distal rectal cancer 45 Gy + 5-FU, 4.9yrs FU

39 Wolthuis AM. Ann Surg Oncol 2012 N=356 stage II and III mid and distal rectal cancer 45 Gy + 5-FU, 4.9yrs FU

40 Predicting pcr? EUS CT PET MRI Tumour Fibrosis Rectal Wall

41 Local excision after CRT? SPTS

42 Local excision after CRT? Author Year pcr (%) Recurrence (%) SV (%) Mohiuddin 94 18T2 30T Kim 02 26T2& Ruo 02 6T2 4T Bonnen 05 26T Lezoche 11 84T Z6401 trial 11 77T2 44 n/a n/a

43 T2N0 TEM vs. TME TEM TME p-value ypt0 28% 26% 0.89 OR time (min) N receiving transfusion 0 20% Hospital stay (d) N=50:50, all T2N0, <3cm, within 6cm from AV, all neoadjuvant radiochemo Lezoche G. BJS 2012

44 T2N0 TEM vs. TME Recurrence (local + distant) Disease-free survival TEM TME TEM TME N=50:50, all T2N0, <3cm, within 6cm from AV, all neoadjuvant radiochemo Lezoche G. BJS 2012

45 Local excision reliable for identifying residual disease? 9.2% 7% 2% 2% 18.6% 8% 4% 15% 21.8% 22% 23% 17% 48.2% 37% 47% 38% 43.7% 67% 48% 33% Chang GJ. ASCO 2011 Stipa F. Ann Surg Oncol 2004 Read TE. DCR 2004 Pucciarelli S. Ann Surg Oncol 2005 Courtesy of Chang GJ.

46 Recurrence Free Survival Recurrence Free Survival Recurrence Free Survival Recurrence Free Survival Impact of TME on disease control with node positive disease A A 1.0 B B P=0.28 P= P=.005 P= ypt0-2n+ N + ypt0-2n0 N Month after Surgery Months After Surgery ypt3-4n+ N + ypt3-4n0 N Months after Surgery Months After Surgery Park et al, ASCRS 2012 Courtesy of Chang GJ.

47 clinical Complete Response (ccr) Whitening : ok Teleangiectasia: ok Loss of pliability of rectum (insufflation): ok No palpable ulcer/nodule/mass No radiological evidence of extrarectsl disease Habr-Gama A. DCR 2010

48 Habr-Gama A. Ann Surg 2004 CLINICAL n (%) Complete 71 (26.8) Incomplete 194 (73.2) PATHOLOGIC n (%) yp0 22 (8.3) ypi 61 (23) ypii 70 (26.4) ypiii 41 (15.5) All rectal cancers 0-7 cm eligible No adjuvant chemotherapy f/u months 2 (2.8%) late endoluminal recurrences (56 & 64 mos.) 3 (4.2%) systemic metastases

49 ccr 21 days 6 weeks 9 weeks 54Gy + 5-FU based chemo x , >7cm from AV, ct2-4 n0-2 M0, median FU 53 month Habr-Gama A. ASCRS (68%) ccr 100% salvaged =62 (51%) non-operative managment 94% overall SV, 75% DFS 8(17%) early re-growth median 7m 4(10%) late recurrence median 21m = Local failure 12 (27%)

50 Watch and wait? NOM: no palpable mass, scarr on endoscopy NOM significant older, more pretreatment morbidity, less stage III NOM 21% LR (11months): 100% salvage surgery 81% in NOM avoided surgery NOM n=32, median FU 28month vs 57/265 (22%) pcr Smith JD. Ann Surg 2012

51 Watch and wait? Local failure Habr- Gama: 3-6% Non Habr-Gama: 33.8% (n=289 patients) Modern studies with systematic FU: 29% (n=92p) Review n=18 Habr-Gama, n=12 non Habr -Gama Glynne-Jones R. BJS 2012

52 Problem: assessing ccr Criteria + timing heterogenous ypt0 correlates partially with N0 (N+ 5-10%) Size of LN poor predictor. 50% N+ <3mm Perez RO. DCR 2009 MRI? mrtrg good response: 72% vs. 27% 5yrs SV DFS 64% vs. 31% Mercurry study Patel UB J Clin Oncol 2011 PET-CT? Variation SUV baseline-12 weeks : >76% ccr (Sensitivity/specificity > 70/80%) Perez RO. ASCRS 2013

53 Problem: assessing ccr ccr correlates poorly with pcr 50% pcr did not have complete ccr Residual mucosal abnormalities <3cm associated with ypt0-1 and <2% N+ Smith FM BJS 2012 Local excison after CRT possible: pcr 45% (3-73), LR 5% (0-23) but might compromises sphincter-saving surgery Studies ongoing (CARTS, ACOSOG Z6041)

54 Surgery for Rectal cancer 2013 If CRM not compromised: Surgery! If CRM compromised: ccr? Interval to TME? Discuss local excision, watch and wait (studies!) TME (lap, robotic)

55 Rectal Cancer: Curative treatment without surgery Not yet Tailored surgery Later? Different? (local excision) but quality controlled