Sepideh Gholami, MD, MAS
ASCO has released its first clinical practice guideline focused specifically on the management of locally advanced rectal cancer.1 “Rectal cancer, and especially locally advanced rectal cancer, is a complex disease that requires individualized approaches using multimodality therapies to have the best oncologic outcomes for our patients,” said Expert Panel Co-Chair Sepideh Gholami, MD, MAS, of Northwell Health, who explained that recent advances have made management more complex than ever.
Aaron J. Scott, MD
According to Expert Panel Co-Chair Aaron J. Scott, MD, of the University of Arizona Cancer Center, in recent years there has been an increasing number of phase II and III clinical trials investigating patients with locally advanced rectal cancer and the use of total neoadjuvant therapy (TNT)—a treatment combination that uses systemic therapy and radiation therapy prior to surgical management.
“This guideline is an attempt to consolidate the various available treatment approaches and provide guidance for the oncologic community,” Dr. Gholami said.
Drs. Gholami and Scott and their colleagues reviewed evidence from 12 randomized controlled trials, 2 systematic reviews, and 1 nonrandomized study on locally advanced rectal cancer published from 2013 to 2023. This available evidence and informal consensus were used to develop evidence-based recommendations.
One of the first goals of the guideline recommendations was to accurately define locally advanced disease, Dr. Gholami said. The recommendation calls for patients to be assessed for microsatellite instability (MSI) or mismatch repair (MMR) status prior to treatment initiation and to undergo high-resolution pelvic magnetic resonance imaging (MRI) to assess for risk factors for recurrence and provide information for surgical planning. It also calls for the use of a standardized synoptic MRI report, which should include relation of the primary tumor to the anal verge, sphincter complex, pelvic nodes, and mesorectal fascia, as well as assessment of extramural vascular invasion, tumor deposits, and lymph nodes.
TNT or Standard Neoadjuvant Chemoradiation?
Next, the panel assessed whether outcomes are improved with TNT compared with standard neoadjuvant chemoradiation for patients with microsatellite stable and/or MMR-proficient locally advanced disease and issued two recommendations.
First, TNT should be offered as initial treatment for patients with low-rectum locally advanced rectal cancer and/or patients at higher risk for local or distant metastases. Second, lower-risk patients with locally advanced middle or upper rectal cancer and a tumor depth of extramural invasion of > 5 mm may be offered neoadjuvant chemotherapy, with selective addition of chemoradiation for patients whose tumors decreased by < 20% in area after chemotherapy, or these patients may opt for chemoradiation as initial neoadjuvant therapy. Differences in adverse events and patient-reported outcomes between chemotherapy alone and chemoradiation can be used to guide treatment choice.
“We found that the TNT approach improved response rates and overall survival for most patients with locally advanced rectal cancer and should be the preferred management strategy when patients can tolerate the approach,” Dr. Gholami said.
Looking at some of the nuances of TNT, the guideline recommends that chemotherapy be given after radiation, based on the results of the OPRA study, which showed a higher rate of total mesorectal excision (TME)-free survival with this approach.2
The panel recommended that if radiation is part of the treatment plan, neoadjuvant long-course chemoradiation is preferred vs short-course radiation therapy; however, the panel noted that it is waiting for the results of several clinical trials, such as ACO/ARO/AIO-18.1 (ClinicalTrials.gov identifier NCT04246684), to provide further guidance on this topic.
Updates Anticipated
Dr. Scott acknowledged that management of locally advanced rectal cancer is a dynamic process, with research on how to optimize and individualize each patient’s care continuing to evolve.
“This guideline is a living document, and there are a couple of areas that we expect to be modified over time because the data are not quite mature or because we need more results,” Dr. Scott said. “One area is nonoperative management, which still remains somewhat controversial, and more investigation is needed to best select patients for this approach.” The recommendation states that nonoperative management may be discussed as an alternative to TME for patients who have a clinical complete response following neoadjuvant therapy.
Another area where more data are needed is the use of immunotherapy, and whether it can be used as an initial approach compared with TNT or other treatment strategies. The guideline recommends immunotherapy for use in tumors that are MSI-high or MMR-deficient.
“The immunotherapy recommendation is based on new data and a small sample size, but the data we do have are promising given the responses seen,” Dr. Scott said. “In terms of making management decisions related to immunotherapy and nonoperative management, more trials will need to be performed.”
References
1. Scott AJ, Kennedy EB, Berlin J, et al: Management of locally advanced rectal cancer: ASCO guideline. J Clin Oncol. August 8, 2024 (early release online).
2. Garcia-Aguilar J, Patil S, Gollub MJ, et al: Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol 40:2546-2556, 2022.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, August 8, 2024. All rights reserved.
