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Response to Misrai et al.

Prostate Cancer and Prostatic Diseases volume 22, pages 182–183 (2019)Cite this article

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We thank Misrai et al. for their interest in and letter about our work. In the sequence of their comments, we offer the following responses. First, the authors are correct that these were post-hoc additional analyses of the REDUCE trial, which never was designed as a study of an intervention for nocturia. This is precisely why we intentionally included the word “observational” in our title. Secondly, although the ICS defines nocturia as one or more voids per night, many epidemiologic studies (e.g., refs. 27–38 in our original paper) have examined not only mortality, but also comorbidities and putative outcomes of nocturia using different thresholds for number of nocturnal voids. As we noted in the paper the association with mortality was not seen with a nocturia threshold of two or more voids (last paragraph of Results), nor was it seen with one or more voids. We do not feel that being beholden to a particular convention, even one established by a highly regarded consensus panel, such as the ICS, negates researchers from examining their data as thoroughly as possible. In that sense, our analyses were indeed very much “data-driven.” Third, as we stated in the fifth paragraph of our Discussion, absence of 24-h frequency volume charts (“bladder diaries”), which often make for a more thorough and comprehensive description of the true frequency of nocturnal voiding, were not used here and is a limitation. Fourth, we fully concur that the obstructive sleep apnea (OSA) could play a partial role in these results. In fact, our group was one of the first to make the observation 15 years ago [1], since replicated by others [2], that nocturia is related to sleep apnea. Whether the MOS sleep questionnaire can specifically substitute for physiologic measurement of OSA is dubious; we agree that most likely it cannot. However, this issue presupposes that OSA underlies the causal pathway between nocturia and mortality. If that is was the case, then treating sleep apnea ought to improve nocturia. Although small, single group studies implies that continuous positive airway pressure (CPAP) treatment of sleep apnea might ameliorate nocturia [3], a relatively large, randomized clinical trial of CPAP could not show that treating sleep apnea improved nocturia [4] Thus, a causal pathway cannot be assumed. Furthermore, there is also well-documented age dependence in OSA, such that the supposed association between OSA and both mortality [5, 6] and various cardiovascular morbidities [7] may be decreased in older age groups, which encompasses the age range of at least some of the participants in REDUCE. Thus, the assumption that the finding that we report is secondary to undiagnosed OSA is suspect at several different levels. Studies of OSA and other sleep disorders among such age groups do serve to remind us, however, that just as Dr. Misrai and colleagues contend, there is still much to be learned about the comorbidities that underpin the complex relationship observed between nocturia and mortality.

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  1. Emory University School of Medicine, Neurology, Atlanta, Georgia, USA

    Donald L. Bliwise

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Correspondence to Donald L. Bliwise.

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Bliwise, D.L. Response to Misrai et al.. Prostate Cancer Prostatic Dis 22, 182–183 (2019). https://doi.org/10.1038/s41391-018-0122-1

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