‘Reply to the letter to the editor ‘Androgen deprivation therapy and risk of rheumatoid arthritis in patients with localized prostate cancer’ by Yang et al.’ by V. Conteduca, U. De giorgi and G. Lauletta
Authors: D.D. Yang, P.L. Nguyen
Journal: Annals of Oncology (2018)

To the Editor, We would like to thank Conteduca, De Giorgi and Lauletta for their interest and insightful comments [1.Conteduca V. De Giorgi U. Lauletta G. Reply to the letter to the editor ‘Androgen deprivation therapy and risk of rheumatoid arthritis in patients with localized prostate can’ by Yang et al.Ann Oncol. 2018; 29: 1879-1880Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar]. The authors note the potential causal link between abnormalities in the structure or regulation of genes encoding TP53 and PTEN in activated synovial fibroblasts and the development of rheumatoid arthritis (RA). Loss or mutation of PTEN is commonly an early event in prostatic carcinogenesis and also portends worse prognosis [2.Khemlina G. Ikeda S. Kurzrock R. Molecular landscape of prostate cancer: implications for current clinical trials.Cancer Treat Rev. 2015; 41: 761-766Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar]. Interestingly, it may be that PTEN alterations underlie a possible association between RA and the development of prostate cancer. The data available to us in Surveillance, Epidemiology, and End Results (SEER)-Medicare database, unfortunately, did not allow us to examine this hypothesis, as all patients in the study cohort had a known diagnosis of prostate cancer [3.Yang D.D. Krasnova A. Nead K.T. et al.Androgen deprivation therapy and risk of rheumatoid arthritis in patients with localized prostate cancer.Ann Oncol. 2018; 29: 386Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. We encourage other investigators with appropriate data sources to examine this question. Additionally, as was noted [1.Conteduca V. De Giorgi U. Lauletta G. Reply to the letter to the editor ‘Androgen deprivation therapy and risk of rheumatoid arthritis in patients with localized prostate can’ by Yang et al.Ann Oncol. 2018; 29: 1879-1880Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar], inflammation status may have important prognostic value for patients with prostate cancer. The authors showed that in a sub-analysis of 551 patients with castration-resistant prostate cancer treated with abiraterone or enzalutamide, 23 patients had pre-treatment autoimmune conditions. Seventeen of these 23 patients had pre-treatment metabolic syndrome or inflammatory alterations (P= 0.045), which was associated with significantly shorter progression-free survival and overall survival (hazard ratio 3.7, 95% confidence interval 2.9–5.9, P< 0.0001 and hazard ratio 5.8, 95% confidence interval 4.0–14.3, P< 0.0001, respectively). These results are notable as it suggests that patients with pre-treatment RA, who are more likely to have a state of increased systemic inflammation, may have worse prostate cancer outcomes, including mortality. Based on these authors’ helpful suggestion, we will undertake a future analysis of the SEER-Medicare database to investigate the association between preexisting RA (before prostate cancer diagnosis) or subsequent diagnosis of RA (after prostate cancer diagnosis) and survival outcomes. Unfortunately, as the SEER-Medicare database does not provide data on serological markers of inflammation, we cannot explicitly examine inflammation status. The authors’ comments highlighting the intriguing, complex, and poorly understood links between inflammation and cancer, including prostate cancer, are timely [4.Sfanos K.S. Hempel H.A. De Marzo A.M. The role of inflammation in prostate cancer.Adv Exp Med Biol. 2014; 816: 153-181Crossref PubMed Google Scholar]. A recent exploratory analysis of a phase III trial found that canakinumab, an inhibitor of interleukin 1β, was associated with lower lung cancer incidence and mortality, as well as total cancer mortality, compared with placebo [5.Ridker P.M. MacFadyen J.G. Thuren T. et al.Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial.Lancet. 2017; 390: 1833-1842Abstract Full Text Full Text PDF PubMed Scopus (709) Google Scholar]. The results of these analyses, though unplanned, have spawned significant interest in the role of anti-inflammatory agents as cancer therapies. Alongside this work, we applaud the efforts of investigators, such as Conteduca, De Giorgi and Lauletta, who have examined the role of inflammation in prostate cancer and encourage others to join this effort. None declared.