Watch and wait approach in rectal cancer: Current controversies and future directions

Abstract

According to the main international clinical guidelines, the recommended treatment for locally-advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery. However, doubts have been raised about the appropriate definition of clinical complete response (cCR) after neoadjuvant therapy and the role of surgery in patients who achieve a cCR. Surgical resection is associated with significant morbidity and decreased quality of life (QoL), which is especially relevant given the favourable prognosis in this patient subset. Accordingly, there has been a growing interest in alternative approaches with less morbidity, including the organ-preserving watch and wait strategy, in which surgery is omitted in patients who have achieved a cCR. These patients are managed with a specific follow-up protocol to ensure adequate cancer control, including the early identification of recurrent disease. However, there are several open questions about this strategy, including patient selection, the clinical and radiological criteria to accurately determine cCR, the duration of neoadjuvant treatment, the role of dose intensification (chemotherapy and/or radiotherapy), optimal follow-up protocols, and the future perspectives of this approach. In the present review, we summarize the available evidence on the watch and wait strategy in this clinical scenario, including ongoing clinical trials, QoL in these patients, and the controversies surrounding this treatment approach.

Keywords: Clinical complete response; Dose intensification; Organ preservation; Rectal cancer; Watch and wait.

Figure 1

Discrepancies in magnetic resonance sequences in follow-up imaging after neoadjuvant therapy. Magnetic resonance imaging (MRI) of the rectum for initial staging (upper row): High-resolution T2 sequences (A), high b value diffusion-weighted imaging (DWI) (B) and apparent diffusion coefficient (ADC) map (C). Protuberant wall thickening (arrow) with an adjacent enlarged, heterogeneous lymph node (arrow); signs of restricted diffusion are observed in both sequences (hyperintensity in DWI and hypointensity in ADC). MRI after neoadjuvant treatment in the same patient (bottom row) reveals near complete resolution of the main mass on the various imaging sequences. In the affected node, fewer morphological alterations are visible, but with no decrease in size (D) and with signs of restricted diffusion (E and F), suggesting persistent malignancy. No evidence of nodal malignancy is evidenced on the histological analysis of the surgical specimen.

Figure 2

Clinical incomplete response. A: Endoscopic evaluation after 9 wk of chemoradiotherapy completion, detecting a small, but irregular, residual ulcer. B: Regrowth is more evident 12 wk later, as a deep, irregular and necrotic ulcer.

Figure 3

Clinical complete response. A: Endoscopic view of a rectal tumor prior to the neoadjuvant chemoradiotherapy; B: Endoscopic ultrasound with radial probe, showing that the tumor (T) is located within the mucosa, submucosa and muscular layers (uT2N0); C: Flat scar 10 wk after treatment completion: An endoscopic response feature.