Benefit of Watch-and-Wait Remains Unclear for Rectal Cancer

Patients with localized rectal cancer are most commonly treated with neoadjuvant therapy (NAT) followed by total mesorectal excision (TME). While this combination is highly effective in reducing risk of metastases and prolonging survival, surgery may be associated with significant morbidity and decreased quality of life. Thus, there is a growing need to develop alternate treatment approaches to avoid surgery when possible. A “watch-and-wait” approach after achieving clinical complete response (cCR) to NAT has been examined in several studies and was shown to be safe and to have promising outcomes. But these studies also had small numbers of patients and short follow-up.

A retrospective case analysis from Memorial Sloan Kettering Cancer Center sought to evaluate long-term outcomes of a watch-and-wait strategy of active surveillance in patients (n = 113) with rectal cancer who achieved cCR following NAT. Outcomes were compared to a cohort of patients (n = 136) who underwent surgical resection after NAT and were found to have achieved a pathologic complete response (pCR). The median follow-up for this analysis was 43 months. The most common NATs were, from most to least common, long-course chemoradiation, induction chemotherapy (8 cycles of FOLFOX) followed by long-course irradiation, and long-course chemoradiation followed by consolidation therapy (8 cycles of FOLOFX). Chemotherapy alone was used only in few patients.

Patients who underwent watch-and-wait strategy after achieving cCR with NAT were generally older than patients who elected for surgery, with cancers closer to the anal verge, and were more likely to have received both induction and consolidation chemotherapy. Active surveillance was associated with a high 5-year rate of rectal preservation (79%). While 91 patients (81% ) in the surveillance group remained free of rectal disease, 22 patients developed local recurrence, which was detected during routine surveillance and resected via salvage surgery. The median time to regrowth was 11.2 months from the date of cCR. The majority (91%) of patients undergoing salvage surgery maintained pelvic control. The cohort of patients treated with NAT and TME surgery (pCR group) experienced no pelvic regrowth. At the end of follow-up, 11 (10%) watch and wait patients had a permanent stoma compared to 21 (15%) in the pCR group.

The five-year rate of overall survival (OS) was 73% for patients in the surveillance group, compared to 94% in the pCR group. Five-year disease-free survival (DFS) was 75% in the surveillance group and 92% in the pCR group, while 5-year disease-specific survival was 90% and 98%, respectively. Patients undergoing surveillance who developed local regrowth were more likely to develop distant metastases following salvage therapy than those who did not develop local regrowth (36% vs 1%; P<.001).

The investigators concluded that a watch-and-wait strategy for patients achieving cCR following neoadjuvant therapy results in rectal preservation and pelvic tumor control, but according to longer follow-up, it is associated with worse OS and higher rates of distant metastases.  They pointed out that better-risk stratification is needed in order to identify those who are at high risk for local relapse and distant progression where the watch-and-wait approach may not be an appropriate choice. In an accompanying editorial note, Charles Thomas, Jr, MD (Oregon Health and Science University, Portland, Oregon, United States), agreed, adding that these data indicate cCR is not a surrogate for pCR. He highlighted that for now, the watch-and-wait approach ‘’may not be in the best interest of patients’’ and should only be used in exceptional situations if a well-trained multidisciplinary team is available to evaluate and closely follow the patient. Results from an ongoing, prospective, randomized, phase II trial that may provide additional information are eagerly awaited.

JAMA Oncol. 2019 Jan 10. [Epub ahead of print].
watch-and-wait-rectal-cancer

Clinical Opinion Poll

How would you treat 52 y/o fit woman with HER2+/HR- breast cancer with progression in lung and CNS (multiple mets) 1 yr after adjuvant pertuzumab/trastuzumab/chemo?