ACE inhibitors associated with superior responses in bladder cancer

A retrospective analysis of patients with muscle-invasive bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC) prior to radical cystectomy found that those who were taking angiotensin-converting enzyme inhibitors (ACEi) experienced increased pathologic complete responses (pCR). Researchers speculated that ACEi may amplify the effects of NAC.

The renin-angiotensin system plays a role in the proliferation of cells, blood cells, and connective tissue; it can also be involved in immunosuppression. Previous studies have suggested that ACEi and angiotensin receptor blockers (ARB) may suppress tumour growth, possibly by blocking transforming growth factor-β, which plays a role in bladder cancer.

Dr Jonathan Thomas (Beth Israel Deaconess Medical Centre, Massachusetts, USA) shared the results of his teams’ retrospective review [1]. The analysis included 133 males and 54 females with MIBC who were either treated or not treated with either ACEi or ARB while they were receiving NAC prior to radical cystectomy for MIBC. Of these 187 patients, 114 (61.0%) were treated with cisplatin/gemcitabine, while 53 (28.3%) received dose-dense methotrexate-vinblastine-adriamycin-cisplatin. Among the patients reviewed, 41 (21.9%) were taking an ACEi, while 24 (12.8%) patients were taking an ARB.

Among the 41 patients taking an ACEi, 17 (41.5%) achieved a pCR versus 36 (24.7%) of the 146 patients who were not taking an ACEi. Multivariable analysis identified only ACEi intake as being associated with pCR. ARB intake was not associated with pCR.

The 5-year overall survival (OS) was 64%. The only factor associated with significantly improved OS was pCR (HR 0.18; 95% CI 0.07–0.45; P<0.001). After adjusting for pCR, ACEi was not significantly prognostic of OS (HR 1.12; 95% CI 0.60–2.09; P=0.72). That is, while ACEi intake was associated with achieving a pCR (OR 2.17; 95% CI 1.05–4.48; P=0.037), it was not prognostic of OS; it was speculated that this finding is due to the presence of other factors which could result in patient death. Both OS and pCR were unaffected by ARB intake while receiving NAC.

Next steps should include validation of these findings with external data. Additionally, investigation should be conducted into the potential impact of ACEi/ARB in other treatment settings of MIBC, including a prospective trial to explore the effect ACEi and ARB intake during NAC treatment.

1. Thomas J. Impact of angiotensin inhibitors on pathologic complete response with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC). Abstract 220, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.

 

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Posted on 24 March 202117 May 2024