Mixed results for watch-and-wait strategy in rectal cancer
medwireNews: Although a watchful waiting approach to rectal cancer surgery is associated with a high rate of rectal preservation among patients who achieve a clinical complete response after neoadjuvant therapy, it may adversely affect survival and also distant control in certain patients, suggests data from a case series.
Philip Paty and colleagues from the Memorial Sloan Kettering Cancer Center in New York, USA, explain that a watch-and-wait strategy is “a nonstandard approach” following attainment of a clinical complete response, “but it has become more widely practiced with the advent of total neoadjuvant therapy and with increasing demand by patients in the context of a [clinical complete response].”
The researchers therefore evaluated the outcomes of 249 patients who received neoadjuvant therapy for rectal adenocarcinoma at their institution between 2006 and 2015, 113 of whom agreed to watchful waiting involving active surveillance and possible salvage surgery, while 136 underwent immediate total mesorectal excision resulting in a pathological complete response.
As reported in JAMA Oncology, the 5-year rate of overall survival was 73% in the watch-and-wait group and 94% in the immediate surgery group; the disease-free survival rates at this timepoint were 75% and 92%, respectively, and the disease-specific survival rates were 90% and 98%.
Twenty-two (19.5%) of the patients undergoing watchful waiting were found to have local recurrence on routine surveillance, compared with none of the patients who had immediate surgery. By contrast, the incidence of distant metastases was more comparable between the groups, at 8% and 4%, respectively.
However, in the watch-and-wait group, distant metastases occurred significantly more often among the 22 patients with local recurrence than the 91 patients without, at rates of 36% versus 1%.
“Whether radical resection after [neoadjuvant therapy] would have mitigated this risk or whether the metastases were formed by early disseminating cancer cells prior to consideration for resection is unknown”, say the study authors.
“Attempting to understand the biology of metastases and local regrowth after [neoadjuvant therapy] will require prospective translational studies with evaluation of clinical and molecular features of the primary, recurrent, and metastatic clones.”
Of note, all 22 watch-and-wait patients with local recurrence underwent salvage surgery – total mesorectal excision in 20 and transanal excision in two individuals – which resulted in freedom from pelvic progression in all but two patients, giving a local control rate of 91% and a rectal preservation rate of 82%.
The study authors therefore conclude that “[a] watch-and-wait strategy may be safe for most patients, but better risk stratification is needed for more precise patient selection to identify those at high risk of local regrowth who are not optimal candidates.”
In an accompanying piece, Charles Thomas Jr (Oregon Health and Science University, Portland, USA) describes the findings as “a helpful data set” that can be used by a multidisciplinary care team and patients as part of the shared decision-making process.
However, he points out that “unless the care team is truly multidisciplinary and thus primed to evaluate, treat, and diligently follow-up patients in a close manner, the [watch-and-wait] approach may not be in the best interest of the patient”, and suggests that physicians “hold tight” until data become available from an ongoing phase II trial by the same investigators.
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