Size of Largest Colorectal Liver Metastasis is an Independent Prognostic Factor After Neoadjuvant Therapy
Key findings
- This retrospective study of a prospectively maintained database evaluated whether the size of the largest colorectal liver metastasis (CRLM) was associated with survival in 214 patients who underwent neoadjuvant chemotherapy and liver resection
- The group with "large" CRLMs (≥21 mm, the median) had worse median disease-free survival (12.5 vs. 16.6 months; P=0.03) and worse disease-specific survival (71.3 vs. 103.5 months; P=0.04) than those with smaller metastases
- On multivariable analysis, having a large CRLM was an independent and significant predictor of poor disease-free survival (HR, 1.58; 95% CI, 1.07–2.35; P=0.02) and poor disease-specific survival (HR, 1.90; 95% CI, 1.23–2.96; P=0.004)
- Other independent predictors of poorer disease-free survival and disease-specific survival were higher primary tumor N-stage, poor response to neoadjuvant chemotherapy, perineural invasion and ≤2 liver metastases
- Size of the largest CRLM is routinely available on preoperative radiologic imaging and even more accurately on the final pathologic report, and may be helpful in prognostication and making decisions about postoperative care such as adjuvant chemotherapy or targeted treatments
When colorectal cancer metastasis is confined to the liver, hepatic resection offers the best chance for cure. Risk scores have been developed to help predict long-term survival, including several that incorporate the size of the largest colorectal liver metastases (CRLM). According to those scores, CRLMs of 50–80 mm were found to be prognostic discriminators in early reports.
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Since the time the scores were created, however, neoadjuvant chemotherapy has been increasingly utilized to shrink CRLM and determine response to treatment prior to surgery. As a result, many patients may have metastases that are smaller than the previously reported cutoffs.
In a more contemporary study conducted in the neoadjuvant setting, Motaz Qadan, MD, PhD, a hepatobiliary and pancreatic surgical oncologist in the Mass General Cancer Center and a surgeon in the Division Gastrointestinal and Oncologic Surgery at Massachusetts General Hospital, and colleagues found that the median size of the largest CRLM noted by pathologists after hepatectomy was 21 mm, and size was associated with cancer-specific survival. Their report appears in the Journal of Surgical Research.
Study Methods
The team reviewed a prospectively maintained database of 214 patients who underwent neoadjuvant chemotherapy and liver resection for CRLM at Mass General between March 2004 and March 2016. Follow-up data on disease-free survival (DFS), which refers to disease recurrence, and disease-specific survival (DSS), which refers specifically to cancer-related mortality, the primary outcomes, were gathered through March 1, 2019.
Correlation Between Metastasis Size and Survival
Median follow-up was 100 months, median DFS was 15 months and median DSS was 93 months.
The median size of the largest liver metastasis per patient was 21 mm (range, 0–170 mm) and the median number of liver metastases per patient was 2 (range, 1–21). By using the median as a cutoff, the cohort was evenly divided into patients with "large" (≥21 mm) or "small" (<21 mm) liver metastases.
The 112 patients with large metastases showed worse median DFS (12.5 vs. 16.6 months; P=0.03) and worse median DSS (71.3 vs. 103.5 months; P=0.04) than the 112 patients with small metastases.
Predictors of DFS
On multivariable analysis, larger liver metastasis size was an independent and significant predictor of poor DFS (HR, 1.58; 95% CI, 1.07–2.35; P=0.02). Other independent risk factors were higher primary tumor N-stage, poor response to neoadjuvant therapy (progressive disease), lymphovascular invasion, perineural invasion, and ≥2 liver metastases.
Predictors of DSS
Similarly, larger liver metastasis size was an independent and significant predictor of poor DSS (HR, 1.90; 95% CI, 1. 23–2.96; P=0.004). Other independent risk factors were higher primary tumor N-stage, poor response to neoadjuvant therapy, perineural invasion and ≥2 liver metastases.
Applying Findings to the Clinic
The size of the largest CRLM is routinely available on the preoperative radiologic imaging and, more accurately, within final pathologic report. This information may be useful in making prognostication decisions about postoperative care such as adjuvant chemotherapy or targeted treatments.
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