Is Malignancy Associated With Arthroplasty? A Meta-analysis.

Abstract

Background: Although implants have been linked to malignancies in other medical contexts, such as the relationship between anaplastic large cell lymphoma and breast implants, the potential association between orthopaedic implants and cancer remains unclear. Several studies have investigated this question, but findings have been inconsistent. A comprehensive meta-analysis is needed to clarify whether total joint arthroplasty increases the risk of malignancy.

Questions/purposes: (1) Is receiving a THA or TKA associated with an increased risk of cancer? (2) Are certain implant types (such as metal-on-metal or cemented) associated with increased cancer risk? (3) Is follow-up duration associated with changes in observed cancer risk estimates?

Methods: A systematic review and meta-analysis were conducted using PubMed, Embase, and SCOPUS to identify studies assessing cancer incidence rates in patients who received hip or knee arthroplasty compared to patients in control groups who did not receive arthroplasty. Databases were queried from inception through the final search date (November 23, 2024). Eligible studies reported or allowed derivation of an effect estimate comparing overall cancer incidence rates in recipients of THA or TKA with an external reference population. From 1838 screened articles, 16 studies were included, all of which provided extractable effect estimates that were entered into one or more of our meta-analyses. Included studies consisted primarily of record-linkage studies connecting national, longitudinally maintained arthroplasty registers to similarly longitudinal national mortality and cancer registers. Study quality was assessed using the Newcastle-Ottawa Scale, which awards up to nine points across three categories, with higher scores indicating lower risk of bias. The 16 included studies scored between 6 and 8 (mean ± SD 7.1 ± 0.8), reflecting generally high methodological quality. The primary analysis included data from 977,465 patients of both sexes and all age groups who underwent hip or knee arthroplasty and were followed up for over 7,415,134 person-years. Effect estimates were pooled with a random-effects model because heterogeneity was present (between-study σ2 = 0.016 versus within-study σ2 = 0.002; Q = 1195, p < 0.001), and a funnel plot showed no evidence of publication bias. To explore associations between implant type and cancer risk for patients undergoing THA, we conducted separate meta-analyses for studies reporting on metal-on-metal bearing surfaces and those reporting on cemented fixation. To assess latency effects, we compared cancer incidence rates in patients with more or less than 10 years of follow-up and conducted a meta-regression to evaluate the association between follow-up duration and cancer risk. We did not perform an a priori power analysis.

Results: Patients who underwent THA or TKA did not have an increased risk of cancer compared with the general population (pooled random-effects estimate [REE] = 0.99 [95% confidence interval (CI) 0.92 to 1.07]; p = 0.88). Subgroup analyses showed no increased cancer risk after TKA (pooled REE = 1.02 [95% CI 0.85 to 1.21]; p = 0.83) or THA (pooled REE = 0.99 [95% CI 0.91 to 1.07]; p = 0.73). Cancer risk did not increase among patients undergoing THA who received cemented implants (pooled REE = 1.00 [95% CI 0.87 to 1.15]; p = 0.93) or metal-on-metal implants (pooled REE = 1.02 [95% CI 0.85 to 1.21]; p = 0.86) compared with the general population. Among patients with ≥ 10 years of follow-up, cancer incidence did not differ from the general population (pooled REE = 1.05 [95% CI 0.97 to 1.14]; p = 0.21); similarly, among patients with < 10 years of follow-up, no increased cancer risk was observed (pooled REE = 0.93 [95% CI 0.81 to 1.06]; p = 0.27). Meta-regression showed no association between follow-up duration and cancer risk (β = -0.004 [95% CI -0.024 to 0.015]; p = 0.66).

Conclusion: Based on these findings, clinicians can continue to recommend arthroplasty without additional cancer-related concern based on current evidence. However, future studies should ensure longer follow-up, improved global representation in large linkage studies, and detailed patient- and implant-specific data to better characterize potential rare or long-latency malignancies.

Level of evidence: Level III, therapeutic study.