The strategy of watch and wait (W&W) in patients with rectal cancer who achieve a complete clinical response (cCR) after neoadjuvant therapy is new and offers an opportunity for patients to avoid ...major resection surgery. However, evidence is based on small-to-moderate sized series from specialist centres. The International Watch & Wait Database (IWWD) aims to describe the outcome of the W&W strategy in a large-scale registry of pooled individual patient data. We report the results of a descriptive analysis after inclusion of more than 1000 patients in the registry.
Participating centres entered data in the registry through an online, highly secured, and encrypted research data server. Data included baseline characteristics, neoadjuvant therapy, imaging protocols, incidence of local regrowth and distant metastasis, and survival status. All patients with rectal cancer in whom the standard of care (total mesorectal excision surgery) was omitted after neoadjuvant therapy were eligible to be included in the IWWD. For the present analysis, we only selected patients with no signs of residual tumour at reassessment (a cCR). We analysed the proportion of patients with local regrowth, proportion of patients with distant metastases, 5-year overall survival, and 5-year disease-specific survival.
Between April 14, 2015, and June 30, 2017, we identified 1009 patients who received neoadjuvant treatment and were managed by W&W in the database from 47 participating institutes (15 countries). We included 880 (87%) patients with a cCR. Median follow-up time was 3·3 years (95% CI 3·1–3·6). The 2-year cumulative incidence of local regrowth was 25·2% (95% CI 22·2–28·5%), 88% of all local regrowth was diagnosed in the first 2 years, and 97% of local regrowth was located in the bowel wall. Distant metastasis were diagnosed in 71 (8%) of 880 patients. 5-year overall survival was 85% (95% CI 80·9–87·7%), and 5-year disease-specific survival was 94% (91–96%).
This dataset has the largest series of patients with rectal cancer treated with a W&W approach, consisting of approximately 50% data from previous cohort series and 50% unpublished data. Local regrowth occurs mostly in the first 2 years and in the bowel wall, emphasising the importance of endoscopic surveillance to ensure the option of deferred curative surgery. Local unsalvageable disease after W&W was rare.
European Registration of Cancer Care financed by European Society of Surgical Oncology, Champalimaud Foundation Lisbon, Bas Mulder Award granted by the Alpe d'Huzes Foundation and Dutch Cancer Society, and European Research Council Advanced Grant.
To evaluate the management and oncological outcomes of rectal cancer patients with local regrowth in a watch-and-wait (W&W) program.
Approximately 15%-30% of patients with a clinical complete ...response after (chemo) radiotherapy who undergo a W&W policy will experience a local regrowth. The risks of these local regrowths have not yet been fully established and main concerns include high postoperative morbidity, requirement of advanced surgery, and pelvic recurrence after regrowth treatment.
All patients with a local regrowth after an initial W&W approach between January 2005 and March 2018 were retrospectively identified from 2 cohorts of rectal cancer patients with a clinical complete response after (chemo) radiotherapy. Type and outcome of regrowth treatment were assessed. Oncological outcome was assessed using Kaplan-Meier estimates.
Eighty-nine out of 385 patients developed a local regrowth after a median of 9 (interquartile range 7-14) months. Median follow-up time was 28 (interquartile range 19-41) months. Eighty-four (94%) patients underwent surgical treatment of the local regrowth: total mesorectal excision was performed in 58 out of 84 (69%) patients and local excision was performed in 26 (31%) patients. The 2-year local recurrence-free rate, distant metastasis-free rate, disease-free survival, and overall survival in the patients undergoing surgical treatment were 97.8%, 91.8%, 90.3%, and 98.4%, respectively.
The vast majority (97%) of patients with regrowth after a W&W policy were able to undergo treatment with curative intent for local regrowth. Uncontrolled pelvic disease was very rare.
Background
To assess whether extending the observation period in patients with a near clinical complete response (near cCR) after chemoradiation (CRT) leads to an impaired oncological outcome.
...Methods
Patients who had a clinical complete response (cCR) 8–10 weeks after CRT restaging with magnetic resonance imaging and endoscopy were offered a watch-and-wait strategy (W&W1), while patients with a near cCR were offered to undergo local excision or a second restaging 6–12 weeks later. Patients who achieved a cCR at the second restaging were also offered a watch-and-wait strategy (W&W2).
Results
Overall, 102 patients with a cCR at the first restaging immediately entered the W&W1, while the remaining 68 patients had a near cCR: 19 patients underwent transanal endoscopic microsurgery and 49 patients opted for a second restaging. Additionally, 44/49 (90%) patients showed a cCR at the second restaging and entered the W&W2. Patients in the W&W1 group had a 2-year local regrowth-free rate (LRFR) of 84% and 2-year overall survival (OS) of 99%, while patients in the W&W2 group had a 2-year LRFR of 73% and OS of 98% (
p
> 0.05). Multivariable Cox regression analyses showed that late inclusion was not a significant predictive factor for higher risk of LR or lower non-regrowth disease-free survival.
Conclusions
Overall, 90% of patients with a near cCR 8–10 weeks after CRT will proceed to a cCR 6–12 weeks later; therefore, it seems logical to extend the observation period rather than to proceed to surgery. Although there is a non-significant increase in local regrowth rate in these patients, it does not seem to impact the oncological outcome.
Objective
The aim of this study was to evaluate whether magnetic resonance imaging (MRI) can accurately identify poor responders after chemoradiotherapy (CRT) who will need to go straight to surgery, ...and to evaluate whether results are reproducible among radiologists with different levels of expertise.
Methods
Seven independent readers with different levels of expertise retrospectively evaluated the restaging MRIs (T2-weighted + diffusion-weighted imaging T2W + DWI) of 62 patients and categorized them as (1) poor responders – highly suspicious of tumor; (2) intermediate responders – tumor most likely; and (3) good – potential (near) complete responders. The reference standard was histopathology after surgery (or long-term follow-up in the case of a watch-and-wait program).
Results
Fourteen patients were complete responders and 48 had residual tumor. The median percentage of patients categorized by the seven readers as ‘poor’, ‘intermediate’, and ‘good’ responders was 21% (range 11–37%), 50% (range 23–58%), and 29% (range 23–42%), respectively. The vast majority of poor responders had histopathologically confirmed residual tumor (73% ypT3-4), with a low rate (0–5%) of ‘missed complete responders’. Of the 14 confirmed complete responders, a median percentage of 71% were categorized in the MR-good response group and 29% were categorized in the MR-intermediate response group.
Conclusions
Radiologists of varying experience levels should be able to use MRI to identify the ± 20% subgroup of poor responders who will definitely require surgical resection after CRT. This may facilitate more selective use of endoscopy, particularly in general settings or in centers with limited access to endoscopy.
Objectives
Rectal cancer patients with a clinical complete response after chemoradiotherapy (CRT) may be followed with a ‘watch-and-wait’ (W&W) approach as an alternative to surgery. MRI plays an ...important role in the follow-up of these patients, but basic knowledge on what to expect from the morphology of the irradiated tumour bed during follow-up is lacking, which can hamper image interpretation. The objective was to establish the spectrum of non-suspicious findings during long-term (> 2 years) follow-up in patients with a sustained clinical complete response undergoing W&W.
Methods
A total of 1509 T2W MRIs of 164 sustained complete responders undergoing W&W were retrospectively evaluated. Morphology of the tumour bed was evaluated (2 independent readers) on the restaging MRI and on the various follow-up MRIs and classified as (a) no fibrosis, (b) minimal fibrosis, (c) full thickness fibrosis, or (d) irregular fibrosis. Any changes occurring during follow-up were documented.
Results
A total of 104 patients (63%) showed minimal fibrosis, 38 (23%) full thickness fibrosis, 8 (5%) irregular fibrosis, and 14 (9%) no fibrosis. In 93% of patients, the morphology remained completely stable during follow-up; in 7%, a minor increase/decrease in fibrosis was observed. Interobserver agreement was excellent (
κ
0.90).
Conclusions
Typically, the morphology as established at restaging remains completely unchanged. The majority of patients show fibrosis with the predominant pattern being a minimal fibrosis confined to the rectal wall. Complete absence of fibrosis occurs in only 1/10 cases. Once validated in independent cohorts, these findings may serve as a reference for radiologists involved in the clinical follow-up of W&W patients.
Key Points
• In rectal cancer patients with a sustained complete response after chemoradiation, the rectal wall morphology as established on restaging MRI typically remains unchanged during long-term MRI follow-up.
• The vast majority of complete responders show fibrosis with the predominant pattern being a minimal fibrotic remnant that remains confined to the rectal wall; complete absence of fibrosis occurs in only 10% of the cases.
• Once validated in independent cohorts, the findings of this study may serve as a reference for radiologists involved in the clinical follow-up of rectal cancer patients undergoing watch-and-wait.
A watch-and-wait approach for patients with rectal cancer and a clinical complete response after neoadjuvant chemoradiotherapy or radiotherapy is associated with better quality of life and functional ...outcome. Nevertheless, prospective data on both parameters are scarce.
To prospectively evaluate quality of life and functional outcome, including bowel, urinary, and sexual function, of patients following a watch-and-wait approach.
A total of 278 patients with rectal cancer and a clinical complete response or near-complete response after neoadjuvant chemoradiotherapy or radiotherapy were included in 2 prospective cohort studies: a single-center study (March 2014 to October 2017) and an ongoing multicenter study (from September 2017). Patients were observed by a watch-and-wait approach. Additional local excision or total mesorectal excision was performed for residual disease or regrowth. Data were analyzed between April 1, 2021, and August 27, 2021, for patients with a minimum follow-up of 24 months.
Quality of life was evaluated with the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 (EORTC-QLQ-C30), EORTC-QLQ-CR38, or EORTC-QLQ-CR29 and 36-Item Short-Form Health Survey. The score for the questionnaires and 36-Item Short-Form Health Survey ranges from 0 to 100. For some scales, a high score indicates a high level of functioning, and for others it indicates a high level of complaints and symptomatology. Functional outcome was assessed by the Low Anterior Resection Syndrome score, Vaizey incontinence score, International Prostate Symptom Score, International Index of Erectile Function, and Female Sexual Function Index.
Of 278 patients included, 187 were male (67%), and the median age was 66 years (range, 34-85 years). In the first 24 months, 221 patients (80%) were observed by a watch-and-wait approach without requiring surgery, 18 patients (6%) underwent additional local excision, and 39 patients (14%) underwent total mesorectal excision. In general, patients observed by a watch-and-wait approach reported good quality of life, with limited variation over time. At 3 months, 56 of 221 patients (25.3%) reported major bowel dysfunction; at 12 months, 53 patients (24.0%) reported it; and at 24 months, 55 patients (24.9%) reported it. At 24 months, 48 of 151 male patients (31.8%) reported severe erectile dysfunction. For female patients, sexual satisfaction and overall sexual function decreased during follow-up. Patients who underwent local excision reported more major bowel dysfunction (10 of 18 patients 55.6%) compared with those without additional surgery. Quality-of-life scores, however, were comparable. After total mesorectal excision, patients scored significantly worse on several quality-of-life subscales.
Results of this study suggest that patients with rectal cancer who were observed by a watch-and-wait approach had good quality of life, with some patients reporting bowel and sexual dysfunction. Quality of life and functional outcome deteriorated when patients required surgery. These data will be useful in daily care to counsel patients on what to expect from a watch-and-wait approach.
The aim was assess the oncological and functional outcome of the watch-and-wait (W&W) approach in older patients with a clinical (near)complete response after neoadjuvant treatment for rectal cancer.
...Patients were included in a W&W-approach (2004–2019) when digital rectal examination, endoscopy and MRI showed a (near)clinical complete response. Patients underwent endoscopy and MRI every 3 months during the first year, and 6-monthly thereafter. Patients aged ≥75 and ≥ 2 years of follow-up (FU) were selected. Oncological outcomes were assessed with Kaplan-Meier curves. Functional outcome was assessed with colostomy-free rate, Vaizey incontinence score, low anterior resection syndrome-score and International Prostate Syndrome Score.
43/304 (14%) of patients in a W&W-approach met the inclusion criteria. Median FU was 37 (24–109) months. 5/43(12%) developed a local regrowth. All were treated surgically, with one patient experiencing a pelvic failure. Distant metastases occurred in 3/43 patients and 4 patients died, 3 of whom not related to rectal cancer. The 3-year local regrowth-free rate was 88%, 3-year non-regrowth disease-free survival 91%, overall survival 97% and 3-year colostomy-free rate 93%. Overall, the bowel- and urinary dysfunction scores at 3, 12 and 24 months indicated good continence, no or minor LARS and moderate urinary problems.
W&W for older patients with a clinical (near) complete response appears to be a safe alternative to a total mesorectal excision (TME), with a very high pelvic control rate, and few rectal cancer related deaths. Most patients can avoid major surgery and a definitive colostomy, and have a reasonable anorectal and urinary function.
•Late dose-volume effects of radiotherapy on the anorectal function were studied in rectal cancer patients.•33.3% of the patients had major LARS (Low Anterior Resection Syndrome).•Clustering and urge ...incontinence were the most common complaints.•Trends towards higher Vaizey and LARS scores after higher doses to the anal sphincter complex were observed.
To assess the long-term anorectal function in rectal cancer patients following a watch-and-wait policy after chemoradiotherapy and to investigate the dose–volume effects of radiotherapy on the anorectal function.
Thirty-three patients with primary rectal cancer who were treated with chemoradiotherapy and a watch-and-wait policy with minimum follow-up of 2 years were included. We assessed the anorectal function using anorectal manometry and patient reported outcomes (Vaizey and LARS score). Dose–volume histograms were calculated for the rectum and anal sphincter complex, and associations between the dose–volume parameters and anorectal function were assessed.
Dmean to the rectum and anal sphincter complex was 50.5 Gy and 44.7 Gy, respectively. After a median follow-up of 38 (range 23–116) months, 33.3% of the patients reported major LARS. Mean LARS score was 23.4 ± 11.3 and mean Vaizey score was 4.3 ± 4.1. The most frequent complaints were clustering of defaecation and faecal urgency. Trends towards a higher Vaizey and LARS score after higher anal sphincter complex dose were observed, although these associations were not statistically significant.
This is the first study to investigate the late dose-volume effects of radiotherapy specifically on the anorectal function in rectal cancer patients. One-third of the patients had major LARS and the most frequent reported complaints were clustering and faecal urgency. Additionally, we observed trends towards worse long-term anorectal function after higher anal sphincter complex radiotherapy dose. However, this should be evaluated on a larger scale. Future efforts to minimise the dose to the sphincters could possibly reduce the impact of radiotherapy on the anorectal function.
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