TY - JOUR
T1 - Defining the Most Informative Intermediate Clinical Endpoints for Patients Treated with Salvage Radiotherapy for Prostate-specific Antigen Rise After Radical Prostatectomy
AU - Martini, Alberto
AU - Fossati, Nicola
AU - Karnes, R. Jeffrey
AU - Boorjian, Stephen A.
AU - Boeri, Luca
AU - Bossi, Alberto
AU - Di Muzio, Nadia
AU - Cozzarini, Cesare
AU - Noris Chiorda, Barbara
AU - Gandaglia, Giorgio
AU - Robesti, Daniele
AU - Bartkowiak, Detlef
AU - Böhmer, Dirk
AU - Shariat, Shahrokh F.
AU - Goldner, Gregor
AU - Battaglia, Antonino
AU - Joniau, Steven
AU - Berghen, Charlien
AU - De Meerleer, Gert
AU - Fonteyne, Valérie
AU - Ost, Piet
AU - Van Poppel, Hein
AU - Montorsi, Francesco
AU - Wiegel, Thomas
AU - Briganti, Alberto
N1 - Publisher Copyright:
Copyright © 2019 European Association of Urology. All rights reserved.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - Intermediate clinical endpoints (ICEs) might aid in trial design and potentially expedite study results. However, little is known about the most informative ICE for patients receiving salvage radiation therapy (sRT) after radical prostatectomy. To investigate the most informative ICE for patients receiving sRT, we used a multi-institutional database encompassing patients treated at eight tertiary centers. Overall, 1301 men with node-negative disease who had not received any form of androgen deprivation therapy were identified. Associations of biochemical (BCR) and clinical recurrence (CR) within 1, 3, 5, and 7yr after surgery with the risk of overall mortality were evaluated using multivariable Cox regression analyses fitted at the landmark points of 1, 3, 5, and 7yr after sRT. The discriminative ability of each model for predicting overall survival (OS) was assessed using Harrell's c index. Median follow-up for survivors was 5.6yr (interquartile range 2.0-8.8). On multivariable analysis, progression to CR within 3yr from sRT (hazard ratio 4.19, 95% confidence interval 1.44-11.2; p= 0.008) was the most informative ICE for predicting OS (c index 0.78) compared to CR within 1, 5, and 7yr (c index 0.72, 0.75, and 0.71). In conclusion, progression to CR within 3yr after sRT, irrespective of the time of surgery, was the most informative ICE for prediction of OS. Our study is hypothesis-generating. If these results are confirmed in future prospective studies and surrogacy is met, this information could be applied for study design and could potentially expedite earlier release of results from ongoing randomized controlled trials. PATIENT SUMMARY: Clinical recurrence of prostate cancer within 3yr after salvage radiation therapy, irrespective of the time of radical prostatectomy, represents the most informative intermediate clinical endpoint for the prediction of overall survival. This information could be applied in the design of future studies and could potentially expedite earlier release of results from ongoing randomized controlled trials.
AB - Intermediate clinical endpoints (ICEs) might aid in trial design and potentially expedite study results. However, little is known about the most informative ICE for patients receiving salvage radiation therapy (sRT) after radical prostatectomy. To investigate the most informative ICE for patients receiving sRT, we used a multi-institutional database encompassing patients treated at eight tertiary centers. Overall, 1301 men with node-negative disease who had not received any form of androgen deprivation therapy were identified. Associations of biochemical (BCR) and clinical recurrence (CR) within 1, 3, 5, and 7yr after surgery with the risk of overall mortality were evaluated using multivariable Cox regression analyses fitted at the landmark points of 1, 3, 5, and 7yr after sRT. The discriminative ability of each model for predicting overall survival (OS) was assessed using Harrell's c index. Median follow-up for survivors was 5.6yr (interquartile range 2.0-8.8). On multivariable analysis, progression to CR within 3yr from sRT (hazard ratio 4.19, 95% confidence interval 1.44-11.2; p= 0.008) was the most informative ICE for predicting OS (c index 0.78) compared to CR within 1, 5, and 7yr (c index 0.72, 0.75, and 0.71). In conclusion, progression to CR within 3yr after sRT, irrespective of the time of surgery, was the most informative ICE for prediction of OS. Our study is hypothesis-generating. If these results are confirmed in future prospective studies and surrogacy is met, this information could be applied for study design and could potentially expedite earlier release of results from ongoing randomized controlled trials. PATIENT SUMMARY: Clinical recurrence of prostate cancer within 3yr after salvage radiation therapy, irrespective of the time of radical prostatectomy, represents the most informative intermediate clinical endpoint for the prediction of overall survival. This information could be applied in the design of future studies and could potentially expedite earlier release of results from ongoing randomized controlled trials.
KW - Biochemical recurrence
KW - Intermediate clinical endpoints
KW - Metastasis
KW - Prostate cancer
KW - Salvage radiation therapy
UR - http://www.scopus.com/inward/record.url?scp=85104900363&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85104900363&partnerID=8YFLogxK
U2 - 10.1016/j.euo.2019.11.003
DO - 10.1016/j.euo.2019.11.003
M3 - Article
C2 - 31810893
AN - SCOPUS:85104900363
SN - 2588-9311
VL - 4
SP - 301
EP - 304
JO - European Urology Oncology
JF - European Urology Oncology
IS - 2
ER -