Watch-and-wait strategy may be appropriate for certain patients with rectal cancer
Click Here to Manage Email Alerts
A nonoperative watch-and-wait strategy appeared comparable to upfront surgery in survival outcomes and could confer a quality-of-life benefit and significant cost savings for certain patients with rectal cancer, according to results of a modeling study published in Journal of the National Cancer Institute.
Researchers observed a preference for upfront total mesorectal excision when surgical salvage rates were low, highlighting a need for standardized surveillance protocols.
“As surgery is quite morbid for these patients with rectal cancer, finding ways to omit surgery is critical for preserving quality of life,” Erqi L. Pollom, MD, MS, assistant professor in the department of radiation oncology at Stanford University, told Healio. “However, it is important that these approaches do not compromise the excellent cancer control outcomes we currently have with multimodality therapy, which is what prompted us to conduct this modeling study that synthesizes the best data we have so far with watch and wait.”
Neoadjuvant chemoradiotherapy followed by total mesorectal excision is considered standard treatment for patients with locally advanced rectal cancer. However, de-escalation of local therapy has garnered interest for patients who achieve clinical complete response with neoadjuvant chemoradiotherapy.
Pollom and colleagues developed a decision-analytic Markov model to assess and compare three management strategies — watch-and-wait surveillance, upfront low anterior resection with temporary defunctioning ileostomy and standard postoperative surveillance, or upfront abdominoperineal resection with permanent colostomy and standard postoperative surveillance — among a cohort of adults with resectable, locally advanced rectal adenocarcinoma who had achieved clinical complete response with standard upfront neoadjuvant chemoradiotherapy.
Researchers pooled data on rates of local regrowth, pelvic recurrence and distant metastasis from studies that compared watch-and-wait with total mesorectal excision after pathologic complete response. They calculated lifetime incremental costs and quality-adjusted life-years between strategies and performed sensitivity analyses to assess model uncertainty.
Results showed a greater proportion of patient deaths among those managed with watch and wait (9.9% vs. 7.5%).
A base case analysis showed 5-year cancer-specific survival rates of 93.5% (95% CI, 91.5-94.9) with watch and wait and 95.9% (95% CI, 93.6-97.4) following upfront total mesorectal excision.
Compared with the low anterior resection approach, the watch-and-wait strategy resulted in a cost savings of $28,500 (95% CI, 22,200-39,000) and incremental QALY of 0.527 (95% CI, 0.138-1.125). Moreover, when compared with abdominoperineal resection, the watch-and-wait strategy produced a cost savings of $32,100 (95% CI, 21,800-49,200) and incremental QALY of 0.601 (95% CI, 0.213-1.208).
Results of sensitivity analyses showed the watch-and-wait strategy remained dominant except for when the rate of surgical salvage decreased to 73%.
“Our data support growing evidence for the safety and acceptability of watch and wait,” Pollom told Healio. “Future research is now looking into how to maximize clinical response rates so that more patients are eligible for the watch-and-wait strategy. We plan to open a phase 2 trial at Stanford University soon to study a regimen of short-course radiation with FOLFOXIRI chemotherapy with a primary objective of maximizing clinical complete response rates.”
Despite the appeal of organ preservation for patients with locally advanced rectal adenocarcinoma, prospective, randomized cooperative group studies are needed to confirm the noninferiority of a watch-and-wait strategy, as well as the applicability of watch and wait to routine community oncological practice, according to a related editorial by Christopher H. Crane, MD, and Paul B. Romesser, MD, PhD, both of the department of radiation oncology at Memorial Sloan Kettering Cancer Center, and Grace Smith, MD, PhD, MPH, of the department of radiation oncology at The University of Texas MD Anderson Cancer Center.
“In Brazil, Cecconello and colleagues are conducting a randomized phase 2 trial comparing the 3-year DFS of [watch and wait] and radical surgery in [patients with locally advanced rectal adenocarcinoma] who achieve a clinical complete response after preoperative chemoradiation. Although this is an important first step, widespread adoption of [watch and wait] will likely be limited, and the use of [watch and wait] will likely remain controversial until randomized phase 3 data demonstrate noninferiority and improved patient-reported outcome.” – by Jennifer Southall
For more information:
Erqi Pollom, MD, MS, can be reached at Stanford University, 875 Blake Wilbur Drive, Stanford, CA 94305; email: erqiliu@stanford.edu.
Disclosures: Pollom reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Romesser reports serving as a consultant for EMD Serono for work on radiation sensitizers. Crane and Smith report no relevant financial disclosures.
Collapse
Crane CH, et al. J Natl Cancer Inst. 2020;doi:10.1093/jnci/djaa005.
Miller JA, et al. J Natl Cancer Inst. 2020;doi:10.1093/jnci/djaa003.
Click Here to Manage Email Alerts