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Source created 2026-08-24 · updated 2026-08-24
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ASCRS Ch26 - Rectal Cancer Neoadjuvant Therapy

Citation

Hunt SR, Mutch MG. Rectal Cancer: Neoadjuvant Therapy. In: Steele SR, et al., eds. The ASCRS Textbook of Colon and Rectal Surgery, 4th ed. Springer; 2022. pp. 463–477 (book pagination; References end p. 477).

Scope

Twenty-sixth chapter of the ASCRS 4th-edition textbook (fourth of Part III, Colorectal Cancer), and the direct specialty-textbook counterpart to this wiki's Total Neoadjuvant Therapy (TNT) page (built from a primary-literature review plus RAPIDO/PRODIGE 23/STELLAR/POLISH II/PROSPECT/GRECCAR16/ JANUS primary publications). Covers the history of (neo)adjuvant radiotherapy for rectal cancer, the foundational randomized trials that established preoperative radiation, the evidence base for adding concurrent chemotherapy to radiotherapy, the limitations of pathologic complete response (pCR) as a surrogate outcome, the induction-vs-consolidation chemotherapy sequencing question within TNT regimens, and short-course radiotherapy combined with systemic chemotherapy.

Key content and reconciliation approach

This chapter's focus differs from Total Neoadjuvant Therapy (TNT)'s in an important way: TNT.md answers "does giving all therapy before surgery beat the traditional CRT→surgery→adjuvant-chemo split," using the four headline phase III TNT trials. This chapter instead answers two prior/ adjacent questions — "does preoperative radiotherapy help at all, and in what form" (the foundational trials, largely pre-dating the TNT concept) and "when multiple neoadjuvant components are combined, what sequencing works best" (concurrent chemoradiation regimen trials, and induction-vs-consolidation sequencing trials). Reconciliation:

  • New "History and foundational trials" section added to TNT.md. The Swedish Rectal Cancer Trial, Dutch Colorectal Cancer Group (TME) trial, the original Polish short- vs. long-course trial, the Trans-Tasman Radiation Oncology Group trial, Stockholm III, and the Chinese FOWARC trial are genuinely new to the wiki — none were previously ingested. These predate or sit outside the TNT trials, establishing the case for preoperative radiotherapy itself and for short- vs. long-course dosing, rather than for TNT specifically. Rectal Cancer's existing "Evolution of treatment" section already covered the German Rectal Cancer Study (preop vs. postop CRT) from the Sabiston chapter — cross-linked, not duplicated.
  • New "Concurrent chemoradiation regimen trials" section added to TNT.md. Lyon R0-04, CALGB 89901, ECOG 3204, STAR-01, NSABP R-04, and German CAO/ARO/AIO-04 establish (with one exception) that adding a second cytotoxic or biologic agent to fluoropyrimidine-based CRT does not improve outcomes and adds toxicity — genuinely new trial-level detail not previously in the wiki, though the practical conclusion (fluoropyrimidine-based CRT is the standard backbone) is consistent with what TNT.md already assumed without sourcing it explicitly.
  • New "Pathologic complete response as a surrogate endpoint" section added to TNT.md, corroborating and formalizing (not duplicating) the pCR/NOM-correlation caveat already present in TNT.md's Surgery and NOM section.
  • Substantially expanded "Consolidation vs. induction chemotherapy sequencing" content added to TNT.md, genuinely new: the Timing of Rectal Cancer Response to Chemoradiation Consortium data, Habr-Gama's original and refined regimens, KONCLUDE, the Spanish GCR-3 trial, the MSKCC TNT retrospective cohort, the Rectal Cancer Consortium induction-vs-consolidation trial, and German CAO/ARO/AIO-12 — none of these were previously ingested, and this sequencing question (induction chemo before CRT vs. consolidation chemo after CRT, both within a TNT framework) is genuinely distinct from TNT.md's existing "Sequence and timing" section, which addresses radiotherapy-vs- chemotherapy-first ordering at a coarser level.
  • Short-course radiotherapy + systemic chemotherapy section: the Washington University pilot and a UK phase II study are new corroborating single-arm/small-trial evidence for the SCRT+chemo approach; the "Polish Colorectal Study Group short-course+FOLFOX vs. long-course" comparison with 7-year follow-up described in this chapter is the same trial already ingested in depth as Ciseł 2019 - POLISH II Long-Term Results — treated as corroboration only, not duplicated.

Limitations

  • Textbook chapter, not primary literature — trial names, designs, and outcome directions are reproduced as described in the chapter; where a trial is already independently ingested from its own primary publication (POLISH II, RAPIDO), that primary source remains authoritative for exact figures and this chapter's mentions are treated as corroboration.
  • Several trials in this chapter (Lyon R0-04, CALGB 89901, ECOG 3204, STAR-01, NSABP R-04, German CAO/ARO/AIO-04, the induction/consolidation sequencing trials) are not independently ingested from primary publications — figures given on Total Neoadjuvant Therapy (TNT) for these trials should be treated as textbook-secondary-source-level, same caveat as this wiki's other ASCRS-textbook- sourced content.
  • German CAO/ARO/AIO-04 reportedly showed a DFS benefit from adding oxaliplatin to fluoropyrimidine- based CRT, while STAR-01 and NSABP R-04 reportedly showed no benefit (and added toxicity) from the same oxaliplatin addition — flagged as an unresolved cross-trial inconsistency rather than silently picking a side (see Total Neoadjuvant Therapy (TNT)'s new Concurrent chemoradiation regimen trials section).

Relevance

Backs a substantial expansion of Total Neoadjuvant Therapy (TNT) with foundational-trial history, concurrent-chemoradiation-regimen evidence, pCR-as-surrogate-endpoint critique, and — most substantively — induction-vs-consolidation chemotherapy sequencing detail. Lightly cross-linked into Rectal Cancer's existing "Evolution of treatment" section.