Risk of developing gallbladder cancer in patients with gallbladder polyps detected on transabdominal ultrasound: a systematic review and meta-analysis

Abstract

Objective: To estimate the risk of malignancy in gallbladder polyps of incremental sizes detected during transabdominal ultrasound (TAUS).

Methods: We searched databases including MEDLINE, Embase, and Cochrane Library for eligible studies recording the polyp size from which gallbladder malignancy developed, confirmed following cholecystectomy, or by subsequent follow-up. Primary outcome was the risk of gallbladder cancer in patients with polyps. Secondary outcome was the effect of polyp size as a prognostic factor for cancer. Risk of bias was assessed using the Quality in Prognostic Factor Studies (QUIPS) tool. Bayesian meta-analysis estimated the median cancer risk according to polyp size. This study is registered with PROSPERO (CRD42020223629).

Results: 82 studies published since 1990 reported primary data for 67,837 patients. 67,774 gallbladder polyps and 889 cancers were reported. The cumulative median cancer risk of a polyp measuring 10 mm or less was 0.60% (99% credible range 0.30-1.16%). Substantial heterogeneity existed between studies (I² = 99.95%, 95% credible interval 99.86-99.98%). Risk of bias was generally high and overall confidence in evidence was low. 13 studies (15.6%) were graded with very low certainty, 56 studies (68.3%) with low certainty, and 13 studies (15.6%) with moderate certainty. In studies considered moderate quality, TAUS monitoring detected 4.6 cancers per 10,000 patients with polyps less than 10 mm.

Conclusion: Malignant risk in gallbladder polyps is low, particularly in polyps less than 10 mm, however the data are heterogenous and generally low quality. International guidelines, which have not previously modelled size data, should be informed by these findings.

Advances in knowledge: This large systematic review and meta-analysis has shown that the mean cumulative risk of small gallbladder polyps is low, but heterogeneity and missing data in larger polyp sizes (>10 mm) means the risk is uncertain and may be higher than estimated.Studies considered to have better methodological quality suggest that previous estimates of risk are likely to be inflated.

Figure 1.

Study selection process.

Figure 2.

Distribution of cancer risk according to gallbladder polyp size measured by transabdominal ultrasound across all included studies. Each dot represents the cancer risk at a particular polyp size for a single study. Studies which reported cancer risk at multiple polyp sizes are depicted by the line connecting the dots associated with the study. The majority of studies showed the risk of cancer to be less than 0.1 for polyp sizes up to 15 mm.

Figure 3.

(a) Meta-analysis summary model showing cumulative risk of gallbladder cancer as a function of polyp size and associated 95% credible interval limits (dashed lines). (b) 95% prediction regions for the estimated cumulative risk. The prediction region covers nearly all the probability space for high thresholds suggesting that the heterogeneity and missing data introduces substantial uncertainty to the model. The summary mean curve and 95% credible region are included but are close to the x-axis. The upper boundary (dashed) is readily apparent, and the lower boundary of the 95% credible region is the dashed line closest to the x-axis.

Figure 4.

Sensitivity analysis of cumulative risk of cancer with credible intervals related to study quality. Studies rated low certainty and above (69 studies; 66,985 patients, 870 cancers) are red. Studies rated moderate certainty and above (13 studies, 51,442 patients, 100 cancers) are blue.