Name of the study
Lateral Nodal Recurrence in Rectal Cancer
Researchers and contact information
Dr. M. (Miranda) Kusters
Other principal investigators
Prof. dr. P.J. (Pieter) Tanis
Prof. dr. C.A.M. (Corrie) Marijnen
Drs. E.G.M. (Eline) van Geffen
Distal rectal cancers have a tendency to spread to lateral lymph nodes (LLNs), especially in cT3/T4 rectal tumours. Enlargement (≥7mm short axis size) of these LLNs has been associated with increased recurrence rates in the lateral compartments in two large retrospective cohort studies (Lateral Node Consortium and Snapshot Rectal Cancer 2016 study). Moreover, intermediate LLNs with malignant features have an increased risk compared to absence of LLNs, but a lower risk than the enlarged group.
These LLNs are located outside the mesorectal fascia, and therefore not adequately treated by neoadjuvant (chemo)radiation and total mesorectal excision (TME) surgery. There is a promising role for lateral lymph node dissection (LLND) to lower this risk, but this challenging procedure requires appropriate training. Moreover, knowledge of lateral nodal disease is still limited among treating clinicians and LLNs are often not reported in MRI reports. Consequently, they often have not been considered for neoadjuvant treatment and often not separately targeted in for neoadjuvant radiotherapy.
In the Netherlands, the multi-disciplinary teams (including radiologists, radiation oncologists, surgeons and pathologists) have been educated and trained to enhance knowledge and awareness of LLNs and to implement nerve-sparing minimally invasive LLND. The LaNoReC describes a prospective evaluation of oncological outcomes after multi-disciplinary training, thereby aiming for a 50% reduction in LLR rates for patients with primarily enlarged LLNs (≥7mm). Additionally, this study aims to prospectively evaluate oncological outcomes of patients with intermediate LLNs and investigate whether there is a role for LLND in this group.
To decrease the LLR rate by dedicated training of the multidisciplinary team and selective LLND with nerve-sparing techniques. The quality of life of patients will also be evaluated.
National prospective registration study
All patients with rectal cancer and one or more enlarged lateral lymph node(s) (a short axis ≥7mm) in the internal iliac or obturator compartment measured on the primary MRI, will be included. Moreover, patients with intermediate lateral lymph node(s) (short axis 5-7mm) and one or more malignant features (irregular margins, loss of fatty hilum, heterogeneity and round shape) will be included. Exclusion criteria are patients younger than 18 years old, previous pelvic irradiation, a previous lateral lymph node dissection for a pelvic malignancy, synchronous metastases, synchronous colon cancer with a higher stage than the rectal cancer, other malignancies in the previous 3 years which could influence oncological outcomes (these patients need to be discussed with the research team before inclusion), an absolute contraindication for general anesthesia, pregnancy or familiar adenomatous polyposis (FAP).
Lateral local recurrence free survival after 3 years
Morbidity, disease free survival, overall survival and quality of life
The sample size is based on the 3-year lateral local recurrence rate of 13% in low cT3/4 rectal cancers with nodes of ≥7mm after CRT + TME only (without LLND). This rate is based on the multicenter Lateral Node Consortium Study and the Snapshot Rectal Cancer 2016 study.
The hypothesis is that this rate can be reduced to <6% with adequate CRT + TME + LLND. With a significance level of 0.05, power of 80% and a drop-out rate of 5%; 200 patients are needed for a 1:1 historical- to treatment-ratio.
Patients with intermediate lateral lymph nodes (5-7mm) and one or more malignant features are included to evaluate long term outcomes, but will not be part of main analyses.
This is a prospective registration study. Therefore, patients will receive the normal standard protocol of care as they would outside of the study. This includes neoadjuvant (chemo)radiotherapy followed by an LLND. The whole multidisciplinary team will be trained in recognizing LLNs, targeting of LLNs with radiotherapy, performing a LLND and assessing the presence of LLNs in the pathological specimen. The indicated surgical treatment is offered to the patients but not compulsory. If the patient and/or physician does not qualify for a LLND or is in need of more extensive surgery (i.e. pelvic exenteration, not nerve sparing), the patient can still be included in the registration arm and will be analyzed separately.
MDT: multidisciplinary team
MRI: Magnetic Resonance Imaging
LLND: lateral lymph node dissection
Amsterdam UMC, locatie VUmc, Amsterdam
Amsterdam UMC, locatie AMC, Amsterdam
More participating centres will follow