Strålebehandling og kjemoterapi gis til pasienter med endetarmskreft med økt risiko for lokalt residiv og/eller fjernmetastaser. Målet er å redusere svulstens størrelse, øke muligheten for radikal kirurgi, begrense omfanget av det kirurgiske inngrepet, redusere risiko for lokalt residiv, og redusere risiko for fjernmetastaser. De senere år har man internasjonalt i økende grad gitt strålebehandling og kjemoterapi med organbevarende intensjon, hvor målet er komplett respons og å unngå operasjon.
Oppsummering av anbefalinger for pasienter med pMMR (MSS) endetarmskreft
Lav-risiko endetarmskreft når man planlegger operasjon
T2/T3 MRF og N0-1 (inkludert glattveggede lymfeknuter ≤ 1mm fra MRF) endetarmskreft ansees som lav-risiko, og pasienter med slike svulster kan opereres direkte med TME, såfremt det ikke foreligger N1c eller EMVI+
Høy-risiko endetarmskreft når man planlegger operasjon
MRF+ foreligger når svulstvev (primærtumor, karinnvekst, tumordepositter eller mesorektale lymfeknuter med irregulær kapsel) har ≤ 1 mm avstand fra MRF.
MRF+, N2, EMVI+, N1c, eller T4a (innvekst i peritoneum) bør vurderes for total neoadjuvant terapi (TNT) med kort strålebehandling 5 Gy x 5 etterfulgt av 6-9 kurer FOLFOX eller 4-6 kurer CAPOX.
Pasienter som ikke anses tåle TNT bør vurderes for preoperativ strålebehandling med 5 Gy x 5 eller CRT.
T4b svulster bør vurderes for TNT med CRT etterfulgt av konsoliderende kjemoterapi med 6-9 kurer FOLFOX eller 4-6 kurer CAPOX.
T4b med innvekst i bakre og laterale kompartment kan være kirurgteknisk utfordrende og bør tilbys TNT i form av induksjonskjemoterapi etterfulgt av CRT for å korte ned tiden mellom stråling og kirurgi.
Pasienter med T4b som ikke forventes tåle TNT bør vurderes for kort strålebehandling eller fortrinnsvis CRT.
Pasienter med lymfeknuter på bekkenveggen med kort-akse ≥ 7 mm på MR bør tilbys TNT. Valg av strålebehandlingsregime kan baseres på primærsvulsten.
Neoadjuvant kjemoterapi alene (6 kurer FOLFOX eller 4 CAPOX) kan vurderes som et alternativ dersom strålebehandling ikke er tilrådelig ved svulster i øvre og midtre rektum og fravær av risikofaktorer for lokalt residiv (T4b, lymfeknuter på bekkenvegg, innvekst i MRF).
Svar på DPYD genotype må foreligge før behandling med 5-FU/kapecitabin (se kapittel «Molekylær og DPYD diagnostikk»). Ved genotype som tyder på redusert eller manglende DPD aktivitet må man følge internasjonale retningslinjer for dosering av 5-FU basert kjemoterapi.
Responsevaluering utføres 6-8 uker etter avsluttet preoperativ strålebasert behandling.
Onkologisk behandling med organbevarende intensjon
Organbevarende behandling forutsetter responsevaluering og oppfølging på universitetssykehus. Forekomst av gjenvekst, lokalt residiv, fjernmetastaser og overlevelse må registreres systematisk.
Opportunistisk organbevarende behandling ved cCR etter onkologisk behandling forutsetter samvalg. Pasienten må informeres om risiko for gjenvekst, at denne øker med økende T-stadium, N+, og EMVI+ og at gjenvekst kan innebære øket risiko for fjernmetastaser.
Intensjonell organbevarende behandling kan vurderes for pasienter med svulster distalt i rektum der alternativet er rektumamputasjon eller for pasienter av annen grunn ønsker å avstå fra operasjon. Beslutningen forutsetter samvalg med pasienten, som må informeres nøye om fordeler og ulemper og risiko for overbehandling. CRT og konsoliderende kjemoterapi foreslås som første valg basert på stadium.
Postoperativ (adjuvant) behandling
Adjuvant CRT kan gis til pasienter som ikke har fått preoperativ behandling ved:
Gjennomført tilstrekkelig lokal reseksjon av intermediær eller høyrisiko pT1 som alternativ til formell kompletterende TME.
Adjuvant kjemoterapi kan gis til pasienter som ikke har fått preoperativ kjemoterapi ved:
pN+ hos pasienter med svulst i øvre rektum
pT4a
Pasienter med per- eller preoperativ tumornær perforasjon som ikke har fått preoperativ behandling bør vurderes for CRT eller eventuelt adjuvant kjemoterapi dersom det også foreligger risikofaktorer for metakrone fjernmetastaser.
Adjuvant kjemoterapi kan gis som FOLFOX eller CAPOX i 3 måneder, eventuelt FLV/kapecitabin i 6 måneder for pasienter som ikke er egnet for oxaliplatin.
Palliativ strålebehandling
Palliativ strålebehandling 5 Gy x 5, eventuelt 3 Gy x 10-13, kan benyttes mot symptomgivende svulster i bekkenet.
Pasienter med dMMR (MSI) endetarmskreft
Pasienter med endetarmskreft med verifisert dMMR/MSI bør vurderes for behandling med immunterapi i form av 6 mnd dostarlimab. Det gjelder spesielt der det er indisert med neoadjuvant behandling eller at kirurgi medfører stomi.
Tabell 13.1: Preoperativ behandling når man planlegger operasjon (pMMR/MSS)
Risiko
Øvre rektum
Midtre/nedre rektum
Lav-risiko
T2-T3, MRF- N0-N1, EMVI-, og N1c-
PME/TME uten forbehandling
TME uten forbehandling1
T2
PME/TME uten forbehandling
Vurdere 5 Gy x 5 / CRT ved T2 MRF+ svulst i nedre rektum
Høy-risiko
MRF+, T4a,
N2, N1c, EMVI+ eller LLN+
5 Gy x 5 etterfulgt av 6-9 FOLFOX eller 4-6 CAPOX2
T4b
CRT etterfulgt/forutgått3 av 6-9 FOLFOX eller 4-6 CAPOX
Ikke egnet for TNT
5 Gy x 5 eller CRT
CRT: kjemoradiasjon (chemoradiation), EMVI: karinnvekst, LLN+: forstørrede lymfeknuter ≥ 7 mm på bekkenveggen, MRF-: svulstvev > 1mm fra mesorektal fascie, MRF+: svulstvev ≤ 1mm fra mesorektal fascie, PME: partiell mesorektal eksisjon TME: total mesorektal eksisjon, TNT: total neoadjuvant terapi.
1Ved mrT2 i nedre rektum kan man henvise til senter som har erfaring med organbevarende endoskopisk behandling
2Neoadjuvant kjemoterapi alene kan vurderes ved svulster i øvre og midtre rektum dersom strålebehandling ikke er tilrådelig og ved fravær av risikofaktorer for lokalt residiv (T4b, LLN+, innvekst i MRF)
3T4b med innvekst i bakre og laterale kompartment bør tilbys TNT i form av induksjonskjemoterapi med 6-9 FOLFOX eller 4-6 CAPOX etterfulgt av CRT.
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