Retrospective data suggest a survival benefit for PTR in synchronous mCC, which is the topic of ongoing prospective trials. Whether outcome after PTR varies by primary tumour sidedness, an important prognostic factor in colorectal cancer (CRC), is currently unknown. We investigated the impact of upfront PTR followed by systemic treatment in synchronous mCC according to sidedness within two randomized phase 3 trials (CAIRO and CAIRO2).
A total of 408 synchronous mCC patients, with available data on both PTR status and sidedness, were included (CAIRO n = 279; CAIRO2 n = 129, excluding patients treated with both bevacizumab and cetuximab). We used mixed effect Cox regression models to study the association between PTR and overall survival (OS) and to estimate hazard ratios (HR). Models were adjusted for age, treatment arm, WHO performance status (PS), serum lactate dehydrogenase (LDH) and year of enrollment as potential confounders. To analyze whether PTR effect was modified by sidedness, we tested the interaction term of PTR status and sidedness.
A total of 191 patients (46.8%) had right-sided mCC and 217 patients (53.2%) had left-sided mCC. The rate of PTR was comparable in right-sided (69.1%) and left-sided (65.0%) mCC. Patients who underwent PTR had better PS and LDH level compared to patients without PTR. Univariable and multivariable analyses demonstrated significant and comparable (pinteraction >0.05) survival benefits after upfront PTR for both right-sided and left-sided mCC (Table).Table: 530P
|HR (95%CI) for OS after PTR versus no PTR|
|Right-sided mCC (n = 191)||Left-sided mCC (n = 217)||pinteraction||Overall effect (n = 408)|
|Univariable||0.53 (0.38-0.73)||0.66 (0.49-0.87)||0.31||0.61 (0.50-0.76)|
|Multivariable||0.60 (0.42-0.84)||0.72 (0.53-0.96)||0.43||0.69 (0.55-0.87)|
The previously reported better survival after PTR among synchronous mCRC patients included in the CAIRO and CAIRO2 trials was significant for all mCC patients in our analysis, independent of sidedness. Prospective randomized trials on the prognostic effect of PTR in synchronous mCC, i.e. the CAIRO4 trial, remain valid for mCC patients with both right- and left-sided primary tumours.
Clinical trial identification
CAIRO: NCT00312000, published: July 14, 2007 (Lancet) CAIRO2: NCT00208546, published: February 5, 2009 (N Engl J Med).
Legal entity responsible for the study
University Medical Center Utrecht, Utrecht, The Netherlands.
Has not received any funding.
All authors have declared no conflicts of interest.