Current Issues and Controversies in the Management of Rectal Cancer

Transcription

1 Current Issues and Controversies in the Management of Rectal Cancer Ghazi M. Nsouli MD 11 th Annual Congress of the Lebanese Society of Gastroenterology November 16, 2012 GMN

2 Staging of rectal cancer Lymphatic Vessel Invasion (L) LX Lymphatic vessel invasion cannot be assessed L0 No lymphatic vessel invasion L1 Lymphatic vessel invasion STAGE GROUPINGS Stage T N M 0 Tis N0 M0 I T1 N0 M0 T2 N0 M0 IIA T3 N0 M0 IIB T4a N0 M0 IIC T4b N0 M0 IIIA T1-T2 N1 M0 T1 N2a M0 IIIB T3-T4a N1 M0 T2-T3 N2a M0 T1-T2 N2b M0 IIIC T4a N2a M0 T3-T4a N2b M0 T4b N1-N2 M0 IV Any T Any N M1 Venous Invasion (V) VX Venous invasion cannot be assessed V0 No venous invasion V1 Microscopic venous invasion V2 Macroscopic venous invasion Perineural Invasion (PN) Present Absent Not recorded R classification RX Presence of residual tumor cannot be assessed R0 No residual tumor R1 Microscopic residual tumor R2 Macroscopic residual tumor Tumor Regression Grade Description Tumor Regression Grade No viable cancer cells 0 (Complete response) Single cells or small groups of cancer cells 1 (Moderate Response) Residual cancer outgrown by fibrosis 2 (Minimal response) Minimal or no tumor kill; extensive residual cancer 3 (Poor response) GMN

3 THE ROLE OF MRI IN STAGING OF RECTAL CANCER GMN

4 MRI vs. Endorectal Ultrasound Limitations of ERUS MRI Small or Very large tumors Very High or Very Low Mass Stenotic Cancer Mesorectal Fascia LN detection < MRI MRI is also performed sans ER device Adapted from Kartik S Jhaveri, MD presentation, WCGI 2012 GMN

5 MRI vs. ERUS S T A G E ERUS VS MRI T1 VS T2 ERUS T2 VS T3 MRI > ERUS A T3 VS T4 MRI >ERUS N MRI >ERUS M CT/PET CT M R I Adapted from Kartik S Jhaveri, MD presentation, WCGI 2012 GMN

6 CT VS MRI CT =Inferior Contrast Resolution Adapted from Kartik S Jhaveri, MD presentation, WCGI 2012 GMN

7 NORMAL MRI ANATOMY T2 Axial Inner High Signal - Mucosa/Submucosa Middle Low Signal Muscularis Propria Outer High Signal Mesorectal Fat Adapted from Kartik S Jhaveri, MD presentation, WCGI 2012 GMN

8 T2 CORONAL MR-Coronal The levatoranimuscle (yellow arrows) and puborectalismuscles (arrow heads). External sphincter (green arrows) and internal sphincter (asterix). Adapted from Kartik S Jhaveri, MD presentation, WCGI 2012 GMN

9 T2 SAGITTAL Adapted from Kartik S Jhaveri, MD presentation, WCGI 2012 GMN

10 Mesorectal Facia Adapted from Kartik S Jhaveri, MD presentation, WCGI 2012 GMN

11 ROLE OF HIGH RESOLUTION MRI Pre-operative road map of tumor T stage ( 2, 3 OR 4) CRM (Circumferential resection margin) Distance from anal verge/sphincter Define Prognostic groups Deciding Preoperative therapy Local Recurrence Risk Adapted from Kartik S Jhaveri, MD presentation, WCGI 2012 GMN

12 Management T1 Transanal Excision T2 TME T3 PreopChemorad+ TME vs. TME + Postop Chemorad T4 Preop Chemorad +Exenteration GMN

13 MRI Accuracy T Staging : % N Staging : % CRM : 95 % Highest Accuracy and Consistency Beets-Tan RG et al. Lancet 2001 Brown G et al. BJS 2003 & RSNA 2004 Nagtegaal I et al Am Surg Path 2002 GMN

14 T Stage T1 s carcinoma in situ T1 invades sub-mucosa T2 invasion of circular/ longitudinal layers T3 invasion through muscularis T4 direct invasion of other organs or visceral peritoneum GMN

15 T3 Circumferential Resection Margin =CRM Adapted from Kartik S Jhaveri, MD presentation, WCGI 2012 GMN

16 T3 : good and bad MRI : >6mm from CRM Pathology >2mm Negative Margin >6 mm CRM CRM 0 GMN Adapted from Kartik S Jhaveri, MD presentation, WCGI 2012

17 Circumferencial Margin and Recurrence The 1 mm cutoff GMN

18 Post treatment prediction of MR CRM status remains of prognostic importance MR CRM involvement associated with 28% local recurrence rate vs 12% if negative after CRT(p=0.013) Patel et al JCO 2011 GMN

19 Canbiopsiesruleout persistingcancer in incomplete clinicalresponse? PPV = 100% NPV = 21% accuracy = 71% Perez RO et al. Colorectal Dis 2012 GMN

20 Kaplan-Meier analysis of survival. (A) Post-treatment pathologic T stage (ypt) and overall survival; (B) yptand disease-free survival; (C) tumor regression grade by magnetic resonance imaging (mrtrg) and overall survival; and (D) mrtrg and disease-free survival Magnetic Resonance Imaging Detected Tumor Response for Locally Advanced Rectal Cancer Predicts Survival Outcomes: MERCURY Experience Uday B. Patel et GMN al J Clin Oncol 29:

21 Radiation or no radiation EFFECT OF RADIATION THERAPY IN EARLY STAGE RECTAL CANCER GMN

22 Neo-adjuvant chemoradiation preferred strategy to further improve local control Sauer R et al. N Engl J Med 2004; 351: GMN

23 Dutch Trial on Effects of Neoadjuvant Radiotherapy 1861 Patients were randomized between to pre-operative radiation therapy (5 Gy x 5 days) followed by TME vs. TME alone. Long term follow up Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial.willem van Gijn et al (Dutch Colorectal Cancer Group) Lancet Oncol 2011; 12: GMN

24 Dutch Trial on Effects of Neoadjuvant Radiotherapy Forest plot analysis of overall survival of subgroups of patients with a negative circumferential resection margin. RT=radiotherapy. TME=total mesorectal excision. HR=hazard ratio Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial.willem van Gijn et al (Dutch Colorectal Cancer Group) Lancet Oncol 2011; 12: GMN

25 Dutch Trial on Effects of Neoadjuvant Radiotherapy On Local Recurrence and Overall Survival (A) Probability of local recurrence in the 1748 eligible patients who underwent a macroscopically complete local resection. (B) Probability of overall survival in the 1805 eligible patients. RT=radiotherapy. TME=total mesorectalexcision. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial.willem van Gijn et al (Dutch Colorectal Cancer Group) Lancet Oncol 2011; 12: GMN

26 Which Radiotherapy PRE-OPERATIVE CHEMO- RADIOTHERAPY VS. POST-OPERATIVE CHEMO-RADIOTHERAPY GMN

27 CONSORT diagram showing the flow of participants through each stage of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial. CRT, chemoradiotherapy Preoperative Versus Postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow-Up of 11 Years. Rolf Sauer et al.,j Clin Oncol 30: GMN

28 Preoperative Versus Postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow-Up of 11 Years. Rolf Sauer et al.,j Clin Oncol 30: GMN

29 Long Term Impact of Various Modalities (A) Overall survival and (B) cumulative incidence of distant recurrences in the intention-to-treat population. CRT, chemoradiotherapy; preop, preoperative; postop, postoperative Preoperative Versus Postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow-Up of 11 Years. Rolf Sauer et al.,j Clin Oncol 30: GMN

30 Long Term Impact of Various Modalities Cumulative incidence of local recurrences after macroscopically complete local tumor resection in the intention-to-treat population (A) and according to treatment received (B). CRT, chemoradiotherapy; preop, preoperative; postop, postoperative. Preoperative Versus Postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow-Up of 11 Years. Rolf Sauer et al.,j Clin Oncol 30: GMN

31 Which Radiotherapy LONG COURSE VS. SHORT COURSE RADIOTHERAPY GMN

32 Duration of Radiotherapy pre-operatively : Australian Study 5 Gyx 5 fractions (1wk) Surgery after 3-7 d FU 425 mg/m2 + LF 20 mg /m2 qd x5 qmx wks After surgery RT total 50.4 Gyover 5 wks And 3 days + FU CI 225 mg/ m2. S Surgery after 4-6 wks Then same RT after surgery X 4 cycles Randomized Trial of Short-Course Radiotherapy Versus Long- Course Chemoradiation Comparing Rates of Local Recurrence in Patients With T3 Rectal Cancer: Trans-Tasman Radiation Oncology Group Trial Samuel Y. Ngan et al J Clin Oncol 30: GMN

33 Any local relapse Recurrence free survival First relapse site Overall survival Australian Study :The trial data indicate that LC may be more effective than SC in reducing the risk of LR, especially for GMN distal tumors 33

34 Which chemotherapy in the neo-adjuvant setting CAPECITABINEVS. 5-FLUOROURACIL (5-FU) GMN

35 Treatment Schema in the trial Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, GMN multicentre, non-inferiority, phase 3 trial Ralf-Dieter Hofheinz et al Lancet Oncol 2012; 13:

36 Disease-free survival and Overall Survival of FU vscapecitabinewith radiation therapy in Rectal Cancer Chemoradiotherapy with capecitabine versus fl uorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial Ralf-Dieter Hofheinz et al Lancet Oncol 2012; 13: GMN

37 FU vs Capecitabine Disease related events Kaplan Meier survival estimates Chemoradiotherapy with capecitabine versus fl uorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial Ralf-Dieter Hofheinz et al Lancet Oncol 2012; 13: GMN

38 Which chemotherapy in the neo-adjuvant setting ADDITION OF OXALIPLATIN GMN

39 Phase 3 trials adding oxaliplatin to preoperative fluorouracil-based chemoradiotherapy in stage 2 3 rectal cancer Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally GMN advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomisedphase 3 trial Claus Röde et al Lancet Oncol 2012; 13:

40 Controversies in Surgery EXTENT OF LYMPH NODE DISECTION GMN

41 Patterns of Lymph node Metastasis in Early Rectal Cancer 30 40% of patients treated for rectal cancer present with lymph-node metastases, which occur along: the mesorectalnodal chain along the inferior mesenteric artery nodes (around 40% of patients), in the lateral pelvic lymph nodes (along the obturator, internal iliac, and medial aspect of the external iliac artery; 10 25% of patients. These particularly in Japan have Extended lymphadenectomy versus conventional surgery for rectal cancer: a meta-analysis Panagiotis Georgiou et al Lancet Oncol 2009; 10: GMN

42 Lateral Lymph Node Disection The obturator fossa after lateral lymph node dissection, with the dissected fatty and connective tissues (right side). Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer (JCOG0212): Dissected fatty and connective tissues including lymph nodes. results from a multicentre, randomised controlled, GMN non-inferiority trial Shin Fujita Lancet Oncol 2012; 13:

43 Long term outcome of extended lymphadenectomy (EL) vs non-el patients : No significant difference Extended lymphadenectomy versus conventional surgery for rectal cancer: a meta-analysis Panagiotis Georgiou et al Lancet Oncol 2009; 10: GMN

44 Controversies in Surgery LAPAROSCOPIC VSOPEN SURGERY GMN

45 Laparoscopic surgery vs. Open surgery post neoadjuvant chemoradiotherapy in rectal cancer Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial Sung-Bum Kang Lancet Oncol 2010; 11: GMN

46 Surgical Data Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial Sung-Bum Kang Lancet Oncol 2010; 11: GMN

47 Pathological Characteristics of Tumors GMN

48 Actual EORTC QLQ-C30 scores On the global quality of life (A) and function scales (B F), higher scores indicate better function. On the symptom scales (G O), higher scores indicate more severe symptoms. Pairs of dots show scores for open surgery (blue) and laparoscopic surgery (red). Dots show mean values and whiskers indicate 95% CI. EORTC=European Organisation for Research and Treatment of Cancer. Preop=preoperative. *p<0 05 in repeated measures ANCOVA adjusted for baseline values. p <0 01 in ANCOVA. Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial Sung-Bum Kang Lancet Oncol 2010; 11: GMN

49 Controversies in Surgery SENTINEL LYMPH NODES BIOPSY GMN

50 Role of Sentinel Lymph node biopsy Stratification by cancer stage showed no significant difference in sensitivity when T1, T2, T3, and T4 tumors were compared: mean sensitivity for colon cancer was 0.79 for pt1, 0.76 for pt2, 0.73 for pt3, and 0.73 for pt4. The number of patients with rectal cancer was too small to stratify by individual T stage; however, pooled sensitivity for T1 and T2 was 0 81 and that for T3 and T4 was When comparing sensitivity for patients with colon (0.86 and rectal cancer (0.82 ) no significant difference was identified (p=0.23) Sentinel-lymph-node procedure in colon and rectal cancer: a systematic review and meta-analysis.martijn H G M van der Pas et al,lancet Oncol 2011; 12: GMN

51 Sensitivity can be increased from 76% (all studies) to 90% for colon and 82% for rectal cancer byfollowing the recommendations Sentinel-lymph-node procedure in colon and rectal cancer: a systematic review and meta-analysis.martijn H G M van der Pas et al, Lancet Oncol 2011; 12: GMN

52 MRI should be mandatory for MDT treatment orientated decisions Detailed prognostic staging T substaging, measure depth, low rectal stage, EMVI, mr CRM and other risk factors Not just T3/T4 Radiology report should account for risk of local recurrence/ distant failure or both. suggest treatment options Audit quality of decisions and quality of imaging reports/ surgery/ histology

53 BACKUP GMN