An organ-preserving approach to treatment after total neoadjuvant therapy (TNT) does not compromise oncologic outcomes in patients with locally advanced rectal adenocarcinoma (LARC), according to research published in the Journal of Clinical Oncology. 

In the phase 2 OPRA trial, researchers found that managing patients with surveillance or total mesorectal excision (TME) based on their response to TNT allowed for organ preservation in roughly half of patients without negatively affecting oncologic outcomes.

The order of chemoradiotherapy (CRT) and systemic chemotherapy did not impact disease-free survival (DFS) in these patients. However, patients who received CRT followed by consolidation chemotherapy (CRT-CNCT) had a higher rate of organ preservation than patients who received induction chemotherapy followed by CRT (INCT-CRT).


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The OPRA trial (ClinicalTrials.gov Identifier: NCT02008656) included 324 patients with stage II or III rectal adenocarcinoma. The patients were randomly assigned to receive INCT-CRT (158 patients) or CRT-CNCT (166 patients). In both cohorts, patients received 4 months of fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5000 to 5600 cGy of radiation in combination with either continuous fluorouracil or capecitabine during radiotherapy.

For both cohorts, TNT was followed by either TME or surveillance, based on tumor response. Patients with a clinical complete response or near-complete response were offered surveillance, while patients with an incomplete response were recommended to undergo TME. The primary endpoint was DFS, and the secondary endpoint was TME-free survival.

There was no significant difference in DFS between the INCT-CRT and CRT-CNCT cohorts (P =.98). The 3-year DFS rate was 76% in both cohorts, which was comparable to the historical 3-year DFS rate of 75%.

There was no significant difference between the INCT-CRT and CRT-CNCT cohorts with regard to local recurrence-free survival (P =.78) or distant metastasis-free survival (P =.67).

Of the 304 patients restaged at the end of TNT, 26% were recommended to undergo TME, and the remaining 74% of patients were offered surveillance. Of the 225 patients initially entered in the surveillance protocol, 40% in the INCT-CRT cohort and 27% in the CRT-CNCT cohort had tumor regrowth during follow-up and were recommended for TME.

The proportion of patients with rectum preservation at 3 years was 53% for the CRT-CNCT cohort and 41% for the INCT-CRT cohort (P =.01). The rate of TME-free survival was 60% in the CRT-CNCT cohort and 47% in the INCT-CRT cohort (P =.02).

The DFS rates were similar in patients who underwent TME after restaging and patients who underwent TME after regrowth, both in the intention-to-treat population (P =.40) and among patients who actually underwent TME (P =.50).

“The potentially rectum-preserving treatment approach for locally advanced rectal cancer appears to be safe in patients with a complete or near-complete response to total neoadjuvant therapy who are willing to undergo a strict surveillance protocol,” the researchers wrote. “This treatment approach can help patients maintain a higher quality of life compared with standard resection-based treatment.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Garcia-Aguilar J, Patil S, Gollub MJ, et al. Organ preservation in patients with rectal adenocarcinoma treated with TNT. J Clin Oncol. Published online April 28, 2022. doi:10.1200/JCO.22.00032

This article originally appeared on Cancer Therapy Advisor