Carcinoma del retto: Highlights
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1 Carcinoma del retto: Highlights Stefano Cordio Struttura Complessa di Oncologia Medica ARNAS Garibaldi Catania Roma 17 Febbraio 2018
2 Disclosures Advisory Committee, research funding and speakers bureau Amgen Inc, Bayer HealthCare, Roche, Merk Serono, Sanofi Genzyme
3 Dimension of rectal cancer The incidence in the UE is per year cases/ population per year Incidence is /year in USA Mortality is 4 10/ population per year Median age at diagnosis remain 70 years
4 13%
5 Which certainty?
6 Specialised and dedicated multidisciplinary team (MDT) of named radiologists, surgeons, radiation oncologists, medical oncologists and pathologists should attend regular meetings and discuss all relevant patients [III, A].
7
8
9 MRI nodal staging c N???
10 1 Poor surgery little mesorectum 2 Average surgery incomplete removal of mesorectum 3 Excellent surgery complete mesorectal excision In/on muscularis In mesorectum Fascial plane
11 Circumferential Resection Margin CRM
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13
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15 Risk profile
16 Consensus statements Early Rectal Cancer Local excision (TEM) If pt1 and no adverse features If adverse histopathology (sm2, G3, V1, L1), requires radical resection (TME) as standard
17
18
19 Consensus statements Rectal cancer ct1-ct2; ct3a/b if middle or high N0 MRF clear, no EMVI Surgery (TME) alone is standard. consider postoperative CRT/CT good
20 Consensus statements Rectal cancer ct3a/b very low, Levators and MRF clear ct3a/b in mid- or high rectum cn1-2 no EMVI TME alone is a standard only if good quality mesorectal resection assured Preoperative SCPRT or CRT followed by TME BRUTTO
21 Consensus statements Rectal Cancer ct3c/d or very low localization levators threatened MRF clear ct3c/d mid-rectum, cn1 N2(extranodal), EMVI posit Limited ct4an0 Preoperative SCPRT or CRT followed by TME, depending on need for regression Molto brutto
22 Consensus statements rectal cancer advanced ct3 with any MRF involved any ct4a/b lateral node positive Preoperative CRT followed by TME Preoperative SCPRT plus FOLFOX and delay to surgery Ugly cattivo
23 Which radiotherapy schedule? Short-course preoperative radiotherapy (SCPRT) with a 25 Gy total dose at 5 Gy/fraction during 1 week, followed by immediate surgery (< 10 days from the first radiation fraction)
24 Which radiotherapy schedule? CRT with a recommended dose of Gy in fractions with optional boost with a further 5.4 Gy in 3 fractions can be considered for preoperative RT if the CRM is threatened
25 Which chemotherapy? Continuous intravenous infusion of 5-Fluorouracil or oral Capecitabine during CRT are recommended rather than bolus 5-FU
26 Which chemotherapy plus 5-FU or Capecitabine? Oxaliplatin added to CRT may slightly increase pathological complete response (pcr) rates and DFS in selected patients, but also enhances acute toxicity Oxaliplatin as a radiosensitizer is not currently recommended to be routinely added to fluoropyrimidine-based CRT (contradictory results and lack of a clear long-term oncological benefit in the seven randomised trials testing this combination) Biological molecularly targeted agents have not been successfully integrated into CRT.
27 Randomized trials with OXA-based CT-RT Trial N Arm pcr TOX G3-4 ACCORD Cape Oxa + RT50 Cape + RT45 19% 14% 25% 11% STAR FUpvi Oxa + RT50 5FUpvi + RT50 16% 16% 24% 8% NSABP-R FP Oxa + RT50 FP + RT50 21% 19% 15% 7% CAO/ARO/AIO FUpvi Oxa + RT50 5FUic + RT50 17% 13% 23% 20% PETACC Cape Oxa + RT45 Cape + RT45 13% 11% NR NR p=0.04 p<0.001
28 Advantages of Pre-operative RT+CT pcr 15% Local recurrence 8% Sphincter preservation surgery 60% 5 year survival 65% Acute toxicity 16%
29
30
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32 Locally Advanced Rectal Cancer
33 Locally Advanced Rectal Cancer We are impacting on LOCAL RECURRENCE 7-10% but NOT on DISTANT METASTASES 24-30%
34
35 Asco GI 2018 rectal cancer : topics Preoperative short course radiotherapy Selective use of Surgery: watch and wait Preoperative (neoadjuvant) chemotherapy Adjuvant chemotherapy after preoperative CRT
36 Asco GI 2018 rectal cancer : topics Preoperative short course radiotherapy Selective use of Surgery: watch and wait Preoperative (neoadjuvant) chemotherapy Adjuvant chemotherapy after preoperative CRT
37 PRO Short-Course RT vs Long-Course CT-RT similar results in LR and OS (if > 6 cm from anal verge) less acute toxicity less expensive more convenient CONTRA No down-staging (early surgery) No combination with CT Late Toxicity
38
39 What is the risk of delaying surgery? Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
40 5x5 with immediate vs delayed surgery Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
41
42 The RAPIDO Trial Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
43 Compliance neoadjuvant CAPOX Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
44 Rapido study Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
45
46 Asco GI 2018 rectal cancer : topics Preoperative short course radiotherapy Selective use of Surgery: watch and wait Preoperative (neoadjuvant) chemotherapy Adjuvant chemotherapy after preoperative CRT
47 SURGERY AFTER COMPLETE RESPONSE TO PRE-OP TREATMENT
48 Non operative management approach Pioneered by Habr-Gama suggests that patients with a clinical complete response to neoadjuvant chemoradiation many have preserved oncologic outcomes and may not derive additional benefit from surgery
49
50
51 Wait & See Local Excision for LARC Mainly retrospective data Heterogeneous trials (staging, patients, Tx, follow up) Short follow up Salvage treatments often unsatisfactory ccr pcr NO TME NO data on mesorectal status LARGE PROSPECTIVE TRIALS ARE NEEDED
52 Accidental organ preservation Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
53 IWWD Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
54 IWWD Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
55 Asco GI 2018 rectal cancer : topics Preoperative short course radiotherapy Selective use of Surgery: watch and wait Preoperative (neoadjuvant) chemotherapy Adjuvant chemotherapy after preoperative CRT
56 Colorectal Cancer Response to Chemotherapy Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
57 Rationale for Neoadjuvant Chemotherapy in Rectal Cancer Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
58
59 Slide 16 Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
60 Neoadjuvant Capecitabine and Oxaliplatin Followed by Synchronous <br />Chemoradiation and TME in MRI Defined Poor Risk Rectal Cancer Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
61 Phase II Randomized Study of chemoradiotherapy followed by surgery and adjuvant CapeOx compared with Induction CapeOx followed by chemort and Surgery in Locally Advanced Rectal Cancer : GCR3 Study Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
62 GCR3 Study Results Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
63 Total Neoadjuvant Therapy in Rectal Cancer: MSK Experience Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
64 Updated Retrospective Review of MSK Experience with Total Neoadjuvant Therapy Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
65 Slide 25 Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
66 Slide 26 Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
67 Slide 28 Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
68
69 Slide 30 Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
70 Asco GI 2018 rectal cancer : topics Preoperative short course radiotherapy Selective use of Surgery: watch and wait Preoperative (neoadjuvant) chemotherapy Adjuvant chemotherapy after preoperative CRT
71 EORTC R A N D O M RT RT+ CT S R A N D O M observation CT
72 EORTC The 5-year cumulative incidence rates for local recurrence were 8.7%, 9.6%, and 7.6% for groups that received chemotherapy preoperatively, postoperatively, or both, and 17.1% in those that did not receive any chemotherapy (p = 0.002) There was no effect on OS or disease-free survival(dfs) with the addition of postoperative chemotherapy compared to no adjuvant chemotherapy (p = 0.32 and 0.29, respectively).
73 437 eligible pts closed because of poor accrual there was no difference in OS, DFS, local recurrence, or distant metastases.
74 Adjuvant therapy in Rectal Cancer Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
75 Adjuvant treatment for rectal cancer Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
76 Meta-analysis of adjuvant chemotherapy in rectal cancer Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
77 Risk of distant metastasis Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
78 Adjuvant chemotherapy for rectal cancer Presented By Cornelis Van De Velde at 2018 Gastrointestinal Cancers Symposium
79 Adjuvant chemotherapy for rectal cancer: considerations Heterogeneity 5FU-based CT Timing Compliance after CT-RT TME Only 75% of pts starts adj-ct Only 50% of pts complete adj-ct
80 Adjuvant Chemotherapy Presented By Andrea Cercek at 2018 Gastrointestinal Cancers Symposium
81 Optimal chemotherapy regimen OXA Fp AIO/ARO/CAO pts 5-FU OXALIPLATIN vs 5-FU DFS HR 0,79 PETACC pts CAPE-OXALIPLATIN vs CAPE DFS HR 0,78 CHRONICLE 120 pts closed poor accrual CAPE-OXALIPLATIN vs OBS DFS HR 0,80 ADORE 321 pts FOLFOX vs 5FU LV DFS HR 0,65
82 Kim, Lancet Oncol 2014
83
84 Adjuvant chemotherapy in rectal cancer Although colon and rectal cancers are frequently grouped as a single disease entity, there are important differences in treatment approaches and patterns of recurrence between these malignancies The role of adjuvant therapy in colon cancers is well established, but available data do not support the routine use of adjuvant chemotherapy in patients with locally advanced rectal cancer receiving neoadjuvant therapy
85 Future Diagnostic tools to better select patients Molecular characteristics Decrease the high metastases rate Evaluation of the late toxicity and functional outcome
86 Grazie per l attenzione
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