Urology

Use of structural equation modelling to demonstrate the differential impact of storage and voiding LUTS on symptom bother and quality-of-life during treatment for LUTS associated with BPH: an integrated analysis of 4 randomized, double-blind placebo-controlled trials

McVary KT, Peterson A, Donatucci CF, Baygani S, Henneges C, Clouth J, Wong D, Oelke M. J Urol 2016; Epub 19 April 2016

Measuring clinical benefit in LUTS/BPH therapy

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are bothersome, but generally respond well to treatment.1

The International Prostate Symptom Score (IPSS) was the first validated symptom questionnaire for LUTS/BPH, and changes in IPSS are an accepted measurement of patients’ response to treatment.1

LUTS broadly fall into two categories:

• Bladder storage LUTS, which include urgency, daytime frequency and nocturia1
• Voiding LUTS, which include poor urinary stream, hesitancy and intermittency.1

Bladder storage LUTS are considered to be more bothersome and detrimental to quality of life (QoL) than voiding LUTS. However, no differential analysis of the impact of storage and voiding LUTS on patient improvement has been documented.1 Sub-score measurements for storing and voiding using the IPSS have not been validated and a potential relationship between these scores has not been determined.1

Using structural equation modelling (SEM) of a randomised, controlled clinical trials database, McVary et al evaluated to what extent storage LUTS contribute to overall LUTS improvement and QoL in men with LUTS/BPH.1

Structural equation modelling for LUTS

Structural equation modelling is a well-accepted statistical method that evaluates how unobserved (latent), difficult-to-measure variables relate to each other and to observed measures resulting from these latent variables.

• Observed variables included age, treatment, seven single IPSS items, IPSS-QoL question and four single BPH Impact Index (BII) items1
• Unobserved (latent) variables included anatomical or physiological parameters associated with storage and voiding, IPSS sub-scores and total BII score.1

To assess the relationships between these variables, the authors analysed pooled clinical trial data from a total of 1,462 men with LUTS/BPH who had participated in four randomised controlled trials.1

Improvements of symptom bother and QoL during treatment for BPH are mainly due to improvements in storage LUTS.1

The SEM had sufficient fit to model relationships between storage LUTS, voiding LUTS, QoL and inconvenience caused by disease symptoms (p<0.0001, probability for test of close fit).1

Results showed that:

• Effects of storage on voiding (0.61; p<0.0001) were 2-fold greater than the effects of voiding on storage (0.28; p<0.0001)1
• Storage had a 2-fold greater direct effect (0.64; p<0.0001) on bother than voiding (0.29; p<0.0001)1
• Symptom bother had the greatest impact on QoL (–0.83) and this effect was largely due to storage improvement (p<0.0001).1

Conclusions

As changes in storage LUTS had a greater impact on QoL and bother than changes in voiding LUTS, the authors suggest that clinical trials of pharmacological treatments for LUTS/BPH should put emphasis on the improvement of storage LUTS.1

Report on: Use of structural equation modelling to demonstrate the differential impact of storage and voiding LUTS on symptom bother and quality-of-life during treatment for LUTS associated with BPH: an integrated analysis of 4 randomized, double-blind placebo-controlled trials. McVary KT, Peterson A, Donatucci CF, Baygani S, Henneges C, Clouth J, Wong D, Oelke M. J Urol 2016; Epub 19 April 2016.