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Lancet Gastroenterol Hepatol. 2018 Dec;3(12):825-836. doi: 10.1016/S2468-1253(18)30301-7. Epub 2018 Oct 12.

Factors affecting local regrowth after watch and wait for patients with a clinical complete response following chemoradiotherapy in rectal cancer (InterCoRe consortium): an individual participant data meta-analysis.

Author information

1
Division of Surgical Oncology and General Surgery, Princess Margaret Hospital and University Health Network, University of Toronto, Toronto, ON, Canada.
2
Manchester Cancer Research Centre and NIHR Manchester Biomedical Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK.
3
Centre for Prognosis Research, Research Institute for Primary Care and Health Sciences, Keele University, Staffordshire, UK.
4
Servicio Cirugia General, Sector de Coloproctologia, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
5
Exeter Colorectal Unit, and Exeter Surgical Health Sciences Research Unit (HESRU), Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, UK.
6
Department of Surgery, Netherlands Cancer Institute, Amsterdam, Netherlands; GROW, School of Oncology and Developmental Biology, University of Maastricht, Maastricht, Netherlands.
7
Department of Radiology, Netherlands Cancer Institute, Amsterdam, Netherlands.
8
Harvard Radiation Oncology Program, Boston, MA, USA.
9
Department of Radiation Oncology, New York University Langone Medical Center, New York, NY, USA.
10
North Wales Cancer Treatment Centre, Rhyl, UK.
11
Clatterbridge Cancer Centre, Liverpool, UK.
12
Royal Liverpool Hospital NHS Foundation Trust, Liverpool, UK.
13
Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
14
Royal Preston NHS Foundation Trust, Preston, UK.
15
Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK.
16
Department of Abdominal and Pelvic Surgery, Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA), Rio de Janeiro, Brazil.
17
Division of Colon and Rectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China.
18
Department of Surgery, Philadelphia VA Medical Center, and Division of Colon and Rectal Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
19
Danish Colorectal Cancer Center South, Vejle Hospital, Vejle, Denmark; Leeds Cancer Centre, St James's University Hospital, and Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
20
Danish Colorectal Cancer Center South, Vejle Hospital, Vejle, Denmark.
21
Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL, USA.
22
Instituto Angelita e Joaquim Gama, São Paulo, Brazil.
23
Ludwig Institute for Cancer Research, Molecular Biology and Genomics Lab, São Paulo, Brazil.
24
Instituto Angelita e Joaquim Gama, São Paulo, Brazil; Ludwig Institute for Cancer Research, Molecular Biology and Genomics Lab, São Paulo, Brazil.
25
Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK; Centre for Prognosis Research, Research Institute for Primary Care and Health Sciences, Keele University, Staffordshire, UK. Electronic address: andrew.renehan@manchester.ac.uk.

Abstract

BACKGROUND:

In patients with rectal cancer who achieve clinical complete response after neoadjuvant chemoradiotherapy, watch and wait is a novel management strategy with potential to avoid major surgery. Study-level meta-analyses have reported wide variation in the proportion of patients with local regrowth. We did an individual participant data meta-analysis to investigate factors affecting occurrence of local regrowth.

METHODS:

We updated search results of a recent systematic review by searching MEDLINE and Embase from Jan 1, 2016, to May 5, 2017, and used expert knowledge to identify published studies reporting on local regrowth in patients with rectal cancer managed by watch and wait after clinical complete response to neoadjuvant chemoradiotherapy. We restricted studies to those that defined clinical complete response using criteria equivalent to São Paulo benchmarks (ie, absence of residual ulceration, stenosis, or mass within the rectum on clinical and endoscopic examination). The primary outcome was 2-year cumulative incidence of local regrowth, estimated with a two-stage random-effects individual participant data meta-analysis. We assessed the effects of clinical and treatment factors using Cox frailty models, expressed as hazard ratios (HRs). From these models, we derived percentage differences in mean θ as an approximation of the effect of measured covariates on between-centre heterogeneity. This study is registered with PROSPERO, number CRD42017070934.

FINDINGS:

We obtained individual participant data from 11 studies, including 602 patients enrolled between March 11, 1990, and Feb 13, 2017, with a median follow-up of 37·6 months (IQR 25·0-58·7). Ten of the 11 datasets were judged to be at low risk of bias. 2-year cumulative incidence of local regrowth was 21·4% (random-effects 95% CI 15·3-27·6), with high levels of between-study heterogeneity (I2=61%). We noted wide between-centre variation in patient, tumour, and treatment characteristics. We found some evidence that increasing cT stage was associated with increased risk of local regrowth (random-effects HR per cT stage 1·40, 95% CI 1·00-1·94; ptrend=0·048). In a subgroup of 459 patients managed after 2008 (when pretreatment staging by MRI became standard), 2-year cumulative incidence of local regrowth was 19% (95% CI 13-28) for stage cT1 and cT2 tumours, 31% (26-37) for cT3, and 37% (21-60) for cT4 (random-effects HR per cT stage 1·50, random-effects 95% CI 1·03-2·17; ptrend=0·0330). We estimated that measured factors contributed 4·8-45·3% of observed between-centre heterogeneity.

INTERPRETATION:

In patients with rectal cancer and clinical complete response after chemoradiotherapy managed by watch and wait, we found some evidence that increasing cT stage predicts for local regrowth. These data will inform clinician-patient decision making in this setting. Research is needed to determine other predictors of a sustained clinical complete response.

FUNDING:

None.

Comment in

PMID:
30318451
DOI:
10.1016/S2468-1253(18)30301-7
[Indexed for MEDLINE]
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