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World Journal of Urology
Published in: World Journal of Urology 2/2020

Open Access 01-02-2020 | Benign Prostatic Hypertrophy | Original Article

Impact of disease progression on individual IPSS trajectories and consequences of immediate versus delayed start of treatment in patients with moderate or severe LUTS associated with BPH

Authors: Salvatore D’Agate, Timothy Wilson, Burkay Adalig, Michael Manyak, Juan Manuel Palacios-Moreno, Chandrashekhar Chavan, Matthias Oelke, Claus Roehrborn, Oscar Della Pasqua

Published in: World Journal of Urology | Issue 2/2020

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Abstract

Purpose

Despite superiority of tamsulosin–dutasteride combination therapy versus monotherapy for lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH), patients at risk of disease progression are often initiated on α-blockers. This study evaluated the impact of initiating tamsulosin monotherapy prior to switching to tamsulosin–dutasteride combination therapy versus immediate combination therapy using a longitudinal model describing International Prostate Symptom Score (IPSS) trajectories in moderate/severe LUTS/BPH patients at risk of disease progression.

Methods

Clinical trial simulations (CTS) were performed using data from 10,238 patients from Phase III/IV dutasteride trials. The effect of varying disease progression rates was explored by comparing profiles on- and off-treatment. CTS scenarios were investigated, including a reference (immediate combination therapy) and six alternative virtual treatment arms (delayed combination therapy of 1–24 months). Clinical response (≥ 25% IPSS reduction relative to baseline) was analysed using log-rank test. Differences in IPSS relative to baseline at various on-treatment time points were assessed by t tests.

Results

Delayed combination therapy initiation led to significant (p < 0.01) decreases in clinical response. At month 48, clinical response rate was 79.7% versus 74.1%, 70.3% and 71.0% and IPSS was 6.3 versus 7.6, 8.1 and 8.0 (switchers from tamsulosin monotherapy after 6, 12 and 24 months, respectively) with immediate combination therapy. More patients transitioned from severe/moderate to mild severity scores by month 48.

Conclusions

CTS allows systematic evaluation of immediate versus delayed combination therapy. Immediate response to α-blockers is not predictive of long-term symptom improvement. Observed IPSS differences between immediate and delayed combination therapy (6–24 months) are statistically significant.
Appendix
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Metadata
Title
Impact of disease progression on individual IPSS trajectories and consequences of immediate versus delayed start of treatment in patients with moderate or severe LUTS associated with BPH
Authors
Salvatore D’Agate
Timothy Wilson
Burkay Adalig
Michael Manyak
Juan Manuel Palacios-Moreno
Chandrashekhar Chavan
Matthias Oelke
Claus Roehrborn
Oscar Della Pasqua
Publication date
01-02-2020
Publisher
Springer Berlin Heidelberg
Published in
World Journal of Urology / Issue 2/2020
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-019-02783-x

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