Watch-And-Wait Strategy Tested For Rectal Cancer Patients With Complete Neoadjuvant Response

Survival may be inferior for rectal cancer patients who postpone surgery after achieving a complete clinical response to neoadjuvant therapy

medwireNews: A case series analysis assessing a watch-and-wait approach to rectal cancer surgery for patients who have achieved a complete clinical response to neoadjuvant therapy suggests that the high rate of rectal preservation may come at the cost of reduced overall survival (OS) and an increased risk of distant metastases in those who experience local recurrence. 

“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”, the study authors write in JAMA Oncology

Five-year OS was 73% for the 113 patients with localised rectal adenocarcinoma who received active surveillance with the possibility of salvage surgery after successful neoadjuvant treatment, most commonly chemoradiotherapy.  

This compared with a 5-year rate of 94% for the 136 patients who underwent immediate total mesorectal excision after neoadjuvant treatment and were found at time of resection to have had a complete pathological response. 

The corresponding rates of disease-free survival were 75% and 92%, with disease-specific survival achieved by 90% and 98%, say Philip Paty, from Memorial Sloan Kettering Cancer Center in New York, USA, and co-investigators. 

None of the patients who underwent surgery directly after neoadjuvant therapy developed pelvic recurrence whereas local regrowth was detected during routine surveillance in 20% of patients in the watch-and-wait arm, resulting in 20 total mesorectal excisions and two transanal excisions. After salvage surgery, pelvic control was maintained in 91% of these cases. Rectal preservation was achieved in 82% of the watch-and-wait arm, the team reports.  

Distant metastases occurred in 8% of the watch-and-wait arm versus 4% of those who received immediate surgery; distant metastases were significantly more common in the watch-and-wait patients who experienced local recurrence than those who did not, at 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”, Philip Paty et al observe.

“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”, they say.

Writing in an editor’s note, Charles Thomas Jr, from Oregon Health and Science University in Portland, USA, says the findings “provide a helpful data set from which a multidisciplinary care team and patients can consider as part of a shared decision-making approach to clinically resectable rectal cancer.” 

But he cautions 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.” 

Until results from a phase II trial from the same research team are available, Charles Thomas Jr recommends clinicians evaluating such patients “hold tight because it is likely that we will have stronger prospective data that may provide a sound foundation for evidence-based recommendations on how best to identify optimal candidates and guidelines for execution of watch-and- wait care in resectable rectal cancer.”

 

References 

Smith JJ, Strombom P, Chow OS, et al. Assessment of a wat ch -and-wait strategy for rectal cancer in patients with a complete response after neoadjuvant therapy . JAMA Oncol; Advance online publication 10 January 2019. doi:10.1001/jamaoncol.2018.5896

Thomas Jr CR. Is watch-and-wait ready for prime time? It depend s on priming of the multidisciplinary care team . JAMA Oncol; Advance online publication 10 January 2019. doi:10.1001/jamaoncol.2018.5895

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