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Fundamentals of Rectal Cancer SurgeryFundamentals of Rectal Cancer Surgery

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Adjuvant Therapy for Rectal Adenocarcinoma

Adjuvant Therapy for Rectal Adenocarcinoma is a topic covered in the Fundamentals of Rectal Cancer Surgery.

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Excluding patients who receive preoperative chemotherapy [e.g. patients receiving total neoadjuvant therapy (TNT)], the current consensus is that clinical stage II/III rectal cancer patients who receive neoadjuvant chemoradiotherapy followed by surgery should also receive routine adjuvant chemotherapy. This recommendation is regardless of pathologic stage, applying even to patients with a pathologic complete response. The rationale for recommending routine adjuvant chemotherapy regardless of pathologic stage is based on concerns that the down-staging of node-positive disease by preoperative radiotherapy may result in node-negative pathologic staging among patients who continue to harbor an increased risk for systemic recurrence. In patients with a diverting ileostomy, the adjuvant chemotherapy is typically given prior to ileostomy closure. This is because the benefit of adjuvant therapy may be less if it is significantly delayed, as might occur if there are surgical complications of the ileostomy closure.

The evidence to support this recommendation derives from trials using modern chemotherapy regimens (FOLFOX), which suggest that adjuvant chemotherapy is associated with superior 3-year disease-free survival rates.[1],[2] Thus, recommendations from the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO) include routine postoperative adjuvant chemotherapy following preoperative chemoradiotherapy for T3–4 and/or node-positive disease.[3],[4] However, data evaluating the benefit of routine adjuvant chemotherapy are not unanimous. In the phase 3 CHRONICLE trial,[5] rectal cancer patients who received neoadjuvant chemoradiation followed by resection were randomized to either XELOX or observation; adjuvant chemotherapy was not associated with an overall survival or a disease-free survival advantage. The Dutch Colorectal Cancer Group (DCCG) trial[6] used a methodology similar to CHRONICLE, with no survival benefit observed in the adjuvant chemotherapy arm. One potential weakness with these two trials was their use of regimens other than FOLFOX or FOLFIRI. While future trials will continue to clarify the benefit of routine adjuvant chemotherapy, current recommendations are for all patients to receive it if they did not receive it prior to surgery in a TNT regimen.

The duration of adjuvant chemotherapy for rectal cancer is usually six months based on data such as the MOSAIC trial,[7] though when patients receive neoadjuvant chemoradiation, adjuvant chemotherapy can be reduced to a duration of only four months without a change to survival rates.[3]

There is a growing interest in providing total neoadjuvant therapy (TNT), which is now a standard option in clinical practice guidelines.[3] The rationale for this is that many patients do not complete recommended chemotherapy after surgery, or receive an incomplete course.[8],[9] In theory, TNT offers improved compliance with chemotherapy, with the potential for improving disease-free survival by decreasing the incidence of distant disease.[10] Additionally, TNT offers the potential for a higher incidence of complete pathologic response, which may potentially allow a larger number of patients to avoid surgery altogether.[11] Data from the RAPIDO trial[12] suggests that TNT may double the incidence of complete pathologic response, with similar findings noted in the PRODIGE 23 study.[13] Both studies demonstrated a superior 3-year disease-free survival among patients treated with TNT compared to conventional adjuvant chemotherapy; however, longer-term data on overall survival is not yet available.

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Excluding patients who receive preoperative chemotherapy [e.g. patients receiving total neoadjuvant therapy (TNT)], the current consensus is that clinical stage II/III rectal cancer patients who receive neoadjuvant chemoradiotherapy followed by surgery should also receive routine adjuvant chemotherapy. This recommendation is regardless of pathologic stage, applying even to patients with a pathologic complete response. The rationale for recommending routine adjuvant chemotherapy regardless of pathologic stage is based on concerns that the down-staging of node-positive disease by preoperative radiotherapy may result in node-negative pathologic staging among patients who continue to harbor an increased risk for systemic recurrence. In patients with a diverting ileostomy, the adjuvant chemotherapy is typically given prior to ileostomy closure. This is because the benefit of adjuvant therapy may be less if it is significantly delayed, as might occur if there are surgical complications of the ileostomy closure.

The evidence to support this recommendation derives from trials using modern chemotherapy regimens (FOLFOX), which suggest that adjuvant chemotherapy is associated with superior 3-year disease-free survival rates.[1],[2] Thus, recommendations from the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO) include routine postoperative adjuvant chemotherapy following preoperative chemoradiotherapy for T3–4 and/or node-positive disease.[3],[4] However, data evaluating the benefit of routine adjuvant chemotherapy are not unanimous. In the phase 3 CHRONICLE trial,[5] rectal cancer patients who received neoadjuvant chemoradiation followed by resection were randomized to either XELOX or observation; adjuvant chemotherapy was not associated with an overall survival or a disease-free survival advantage. The Dutch Colorectal Cancer Group (DCCG) trial[6] used a methodology similar to CHRONICLE, with no survival benefit observed in the adjuvant chemotherapy arm. One potential weakness with these two trials was their use of regimens other than FOLFOX or FOLFIRI. While future trials will continue to clarify the benefit of routine adjuvant chemotherapy, current recommendations are for all patients to receive it if they did not receive it prior to surgery in a TNT regimen.

The duration of adjuvant chemotherapy for rectal cancer is usually six months based on data such as the MOSAIC trial,[7] though when patients receive neoadjuvant chemoradiation, adjuvant chemotherapy can be reduced to a duration of only four months without a change to survival rates.[3]

There is a growing interest in providing total neoadjuvant therapy (TNT), which is now a standard option in clinical practice guidelines.[3] The rationale for this is that many patients do not complete recommended chemotherapy after surgery, or receive an incomplete course.[8],[9] In theory, TNT offers improved compliance with chemotherapy, with the potential for improving disease-free survival by decreasing the incidence of distant disease.[10] Additionally, TNT offers the potential for a higher incidence of complete pathologic response, which may potentially allow a larger number of patients to avoid surgery altogether.[11] Data from the RAPIDO trial[12] suggests that TNT may double the incidence of complete pathologic response, with similar findings noted in the PRODIGE 23 study.[13] Both studies demonstrated a superior 3-year disease-free survival among patients treated with TNT compared to conventional adjuvant chemotherapy; however, longer-term data on overall survival is not yet available.

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Last updated: September 20, 2021

Citation

"Adjuvant Therapy for Rectal Adenocarcinoma." Fundamentals of Rectal Cancer Surgery, 2021. ASCRS U, www.ascrsu.com/ascrs/view/Fundamentals-of-Rectal-Cancer-Surgery/2831024/all/Adjuvant Therapy for Rectal Adenocarcinoma.
Adjuvant Therapy for Rectal Adenocarcinoma. Fundamentals of Rectal Cancer Surgery. 2021. https://www.ascrsu.com/ascrs/view/Fundamentals-of-Rectal-Cancer-Surgery/2831024/all/Adjuvant Therapy for Rectal Adenocarcinoma. Accessed March 22, 2023.
Adjuvant Therapy for Rectal Adenocarcinoma. (2021). In Fundamentals of Rectal Cancer Surgery https://www.ascrsu.com/ascrs/view/Fundamentals-of-Rectal-Cancer-Surgery/2831024/all/Adjuvant Therapy for Rectal Adenocarcinoma
Adjuvant Therapy for Rectal Adenocarcinoma [Internet]. In: Fundamentals of Rectal Cancer Surgery. ; 2021. [cited 2023 March 22]. Available from: https://www.ascrsu.com/ascrs/view/Fundamentals-of-Rectal-Cancer-Surgery/2831024/all/Adjuvant Therapy for Rectal Adenocarcinoma.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Adjuvant Therapy for Rectal Adenocarcinoma ID - 2831024 Y1 - 2021/09/20/ BT - Fundamentals of Rectal Cancer Surgery UR - https://www.ascrsu.com/ascrs/view/Fundamentals-of-Rectal-Cancer-Surgery/2831024/all/Adjuvant Therapy for Rectal Adenocarcinoma DB - ASCRS U DP - Unbound Medicine ER -
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Grapherence® [↑11]
    • Fundamentals of Rectal Cancer Surgery
    • Background
    • Rectal Anatomy
    • Rectal Cancer Biology and Hereditary Cancer Syndromes
    • Rationale for Multi-Modality Therapy
    • Preoperative Issues
    • Preoperative Staging
    • Role of Tumor Board
    • Indications for Preoperative Neoadjuvant Therapy
    • Local Excision
    • Indications for LAR Versus Intersphincteric Resection Versus APR
    • Indications for Extended Resection
    • Preoperative Preparation
    • Interoperative
    • Patient Positioning and Equipment for Rectal Cancer Surgery
    • Inferior Mesenteric Artery
    • Inferior Mesenteric Vein (IMV)
    • Splenic Flexure Mobilization
    • Surgical Techniques for Length
    • Technique of Total Mesorectal Excision (TME)
    • Tailored Mesorectal Excision (TME)
    • Bowel Transection and Anastomosis
    • Indications for Fecal Diversion
    • Abdominoperineal Resection
    • Standardized Operative Report
    • Management of Intraoperative Vascular and Urinary Complications
    • Postoperative Issues
    • Rectal Cancer Pathology Assessment
    • Adjuvant Therapy for Rectal Adenocarcinoma
    • Surveillance After Rectal Cancer Treatment
    • Management of Local Recurrences
    • Short-Term Complications - Anastomotic
    • Short-Term Complications - Urinary
    • Ostomy Complications and Management
    • Long-Term Complications – Bowel Dysfunction
    • Long-Term Complications - Sexual Dysfunction and Its Management
    • Parastomal and Perineal Hernias
    • Impact of Postoperative Complications On Oncologic Outcomes
    • Course Complete
    • Final Assessment
Grapherence® [↑11]
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Related Topics

  • Rectal Cancer: Neoadjuvant Therapy
  • Rectal Cancer: Local Excision
  • Colorectal Cancer: Postoperative Adjuvant Therapy and Surveillance
  • Surveillance and Survivorship Care of Patients After Curative Treatment of Colon and Rectal Cancer
  • Rationale for Multi-Modality Therapy
  • Gastrointestinal Stromal Tumors, Neuroendocrine Tumors, and Lymphoma
  • Local Excision
  • Management of Rectal Cancer
  • Management of Local Recurrences
  • Preoperative Staging
more...
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