Lateral Nodal Recurrence in Rectal Cancer
Lateral Nodal Recurrence in Rectal Cancer
Local recurrence rates in rectal cancer have reduced dramatically since the introduction of
 the total mesorectal excision (TME) technique and neoadjuvant chemoradiotherapy (CRT) to
 overall rates of 5-year local recurrence to 5-10%.

 However, distal rectal cancers have a tendency to spread to lateral lymph nodes and it was
 recently shown that patients with enlarged lateral lymph nodes of ≥7 mm have a considerable
 chance of a local recurrence, 19.5% in 5 years regardless of CRT with TME. If the enlarged
 (>7mm) lateral lymph node was reduced to <4mm (internal iliac) or <6mm (obturator), none of
 the patients developed a local recurrence, while lymph nodes that stayed enlarged in the
 internal iliac compartment had a local recurrence rate over 5 years of 52.3%. This rate was
 significantly reduced to 8.7% when performing a lateral lymph node dissection (LLND) to (C)RT
 + TME.

 A major drawback of this recent multi-center study is its retrospective nature, for example,
 while each center has general guidelines for irradiating lateral nodal compartments, it might
 be possible that these lymph nodes were not always included in the irradiation fields.

 The LaNoReC trial is a prospective registration study aimed at increasing national awareness
 for enlarged lateral nodes and their role in local recurrences. The main question of this
 study is whether, after standardized and quality controlled irradiation of the lateral nodes
 and selective LLNDs performed in an expertise center, the lateral local recurrence rate in
 rectal cancers with nodes with a short-axis of ≥ 7 mm can be reduced to below 6%.
Local recurrence rates in rectal cancer have reduced dramatically since the introduction of
 the total mesorectal excision (TME) technique. These rates have been lowered further with the
 use of neoadjuvant (chemo)radiotherapy ((C)RT) regimens in appropriate cases, decreasing
 overall rates of 5-year local recurrence to 5-10%. Western surgeons have always relied on
 (C)RT to sterilize the lateral compartment, containing the internal iliac and obturator lymph
 nodes, alleviating fears of operative morbidity and nerve function disorders associated with
 a lateral lymph node dissection (LLND), mainly performed in the East. Furthermore, most
 western clinicians consider lateral nodal disease to represent metastatic disease, not
 amendable to cure.

 Recently, the lateral node study consortium undertook a multi-centre study with 12 centres
 from seven countries, collecting data over a 5-year period, including all consecutive
 patients operated for a cT3 or T4 rectal cancer. In all patients, every series of MRI's was
 re-reviewed by a standardized protocol, examining lateral pelvic nodes, defining these
 according to size and the presence of malignant features and relating these to the
 development of locally recurrent disease.

 In the first publication of the consortium with a total of 1216 patients, it was shown that
 pre-treatment lateral lymph node (LLN) size of ≥7 mm, results in an unacceptably high
 incidence of lateral local recurrence of 19.5%, despite (C)RT with TME. Within the
 consortium, several centres performed LLND's after (C)RT, which resulted in a significantly
 lower rate of lateral local recurrence of 5.7% in nodes ≥7 mm (p = 0.042). Furthermore, LLN
 enlargement did not influence distant metastases rate, suggesting it is a local issue which
 requires to be addressed through targeted treatment in the pelvis, rather simply representing
 a marker of poor prognosis and distant disease.

 To assess the value of restaging MRI, patients who underwent (C)RT and had a restaging MRI
 were then selected, leaving 741 for analyses: 651 had (C)RT+TME, 90 underwent (C)RT+TME+LLND.
 96 patients (14.7%) had nodes ≥7 mm in short-axis on primary MRI (pre-SA). At 3 years after
 surgery, there were no lateral local recurrences in 28 patients (29.2%) with nodes that had a
 short-axis of ≤ 4 mm on restaging MRI (post-SA). There was an important difference between
 the nodes located in the internal iliac compartment versus the ones in the obturator
 compartment. In the internal iliac nodes, there was only a 22% chance of becoming ≤ 4 mm.
 Pre-SA ≥ 7 mm and post-SA > 4 mm in the internal iliac compartment resulted in a 5-year
 lateral local recurrence rate of 52.3%. Adding LLND to (C)RT+TME in these malignant internal
 nodes, resulted in a significantly lower 8.7% lateral recurrence rate (p = 0.0071). For the
 nodes in the obturator compartment, the chance of becoming ≤ 4 mm was 36%, but even in the
 nodes ≤ 6 mm (63%) there was a 0% chance of lateral local recurrence. If the nodes however
 remained post-SA > 6 mm, the chance of lateral local recurrence was 17.8%. This was reduced
 to 0% after a LLND.

 The major drawback of this multi-center study is its retrospective nature and although the
 general guidelines of each center stated that in these types of rectal cancers would always
 have the lateral nodal compartments in the irradiation volume, this remains uncertain.
 Furthermore, whether these lymph nodes were always included for each individual patient and
 whether the node(s) were boosted was impossible to find out. It might be that the internal
 iliac were not always included in the irradiation volume, explaining the low response rate
 and the high lateral local recurrence rate. Also, although it was reconstructed from the
 operation reports that all patients had a complete formal LLND, surgery was not standardized,
 not guaranteeing clearance of all nodes with formal anatomical landmarks and boundaries of
 the dissection.

 The goal of this study is to raise national awareness in the Netherlands that even small
 lateral nodes (7mm) can cause lateral local recurrence if not treated adequately. The main
 question of this study is, whether after standardized and quality controlled irradiation of
 the lateral nodes and selective LLND performed in an expertise center, the lateral local
 recurrence rate in rectal cancers with nodes with a short-axis of ≥ 7 mm can be reduced to
 below 6%.
Inclusion Criteria:

 -  All patients with rectal cancer with one or more lateral nodes with a short-axis of
 ≥7mm.

 MR images are reviewed by a one of the study radiologists and both the nodes in the
 internal iliac as the obturator compartment are assessed. The largest node in each
 compartment is used as the reference short-axis in the flow charts. If there are both ≥7mm
 internal iliac and obturator nodes, the internal iliac flowchart is used

 Exclusion Criteria:

 -  Younger than 18 years old

 -  Pelvic irradiation in the medical history

 -  Previous lateral lymph node dissection related to pelvic malignancy

 -  Synchronous distant metastases

 -  Familiar adenomatous polyposis

 -  Synchronous colon cancer with a higher stage than rectal cancer

 -  Absolute contraindication for general anaesthesia

 -  Pregnancy