Prevalence and risk factors of persistent cough in patients diagnosed with renal cell carcinoma: a systematic review and meta-analysis.

objectivesCough occurring in patients with renal cell carcinoma (RCC) was first described in 1935 and is a frequently discussed symptom on patient forums. We aimed to systematically review the available evidence to explore the prevalence and risk factors for persistent cough in patients diagnosed with RCC to establish whether cough could be a presenting symptom of RCC.

designThis epidemiological systematic review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement 2020. DATA SOURCES: Medline, Embase, Science Citation Index, The Cochrane Library, ClinicalTrials.gov and the WHO trials register were searched without language restrictions until 1 June 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included articles of all study designs reporting cough in patients (18 years or older) with RCC attributed to the disease itself or to treatment. DATA EXTRACTION AND SYNTHESIS: Data from included articles was extracted using a preprepared and piloted form, and quality assessment was conducted independently by two authors. The risk of bias was assessed in studies other than case reports or case series using the critical appraisal instrument for studies reporting prevalence data. Narrative techniques were used for data analysis and, where appropriate, meta-analysis using a fixed-effects model was performed.

resultsOf 509 studies screened, 105 full-text articles were assessed, with 46 papers subsequently excluded, resulting in 59 analysed in depth. There were 105 patients with RCC reported as having a cough due to the disease itself within 30 case reports and 8 case series. When present, most coughs were described as persistent and dry in nature. The cause of cough was attributed to various aetiologies including pulmonary and endobronchial metastasis and paraneoplastic syndromes. Studies reporting patients with RCC developing a cough because of systemic treatment were heterogeneous. Two studies with 238 patients on temsirolimus and 230 on interferon-α (IFN-α) were suitable for meta-analysis using a fixed-effects model. Patients on temsirolimus were more likely to develop a cough than those on IFN-α (OR 1.95 with a 95% CI of 1.05 to 3.63, overall effect Z=2.12 (p=0.03), I

conclusionCough can occur in patients with RCC, as part of the disease pathogenesis, as an adverse effect of systemic treatment or due to unrelated causes such as pre-existing conditions (eg, asthma). Further research is required to determine the true prevalence and cause and to assess whether cough could be a presenting symptom for RCC. PROSPERO REGISTRATION NUMBER: CRD42022302962.