TY - JOUR
T1 - Use of Concomitant Androgen Deprivation Therapy in Patients Treated with Early Salvage Radiotherapy for Biochemical Recurrence After Radical Prostatectomy
T2 - Long-term Results from a Large, Multi-institutional Series
AU - Gandaglia, Giorgio
AU - Fossati, Nicola
AU - Karnes, R. Jeffrey
AU - Boorjian, Stephen A.
AU - Colicchia, Michele
AU - Bossi, Alberto
AU - Seisen, Thomas
AU - Cozzarini, Cesare
AU - Di Muzio, Nadia
AU - Noris Chiorda, Barbara
AU - Zaffuto, Emanuele
AU - Wiegel, Thomas
AU - Shariat, Shahrokh F.
AU - Goldner, Gregor
AU - Joniau, Steven
AU - Battaglia, Antonino
AU - Haustermans, Karin
AU - De Meerleer, Gert
AU - Fonteyne, Valérie
AU - Ost, Piet
AU - Van Poppel, Hendrick
AU - Montorsi, Francesco
AU - Briganti, Alberto
N1 - Publisher Copyright:
© 2017 European Association of Urology
PY - 2018/4
Y1 - 2018/4
N2 - Background: Hormonal manipulation concomitant to salvage radiotherapy (SRT) given for biochemical recurrence (BCR) after radical prostatectomy (RP) improved outcomes in two randomized trials. However, neither of these studies focused on men treated at low prostate-specific antigen (PSA) levels. Objective: To test if the impact of androgen deprivation therapy (ADT) on metastasis in patients undergoing early SRT varies according to prostate cancer (PCa) features. Design, setting, and participants: A total of 525 patients received SRT at PSA levels ≤2 ng/ml. Outcome measurements and statistical analyses: Multivariable Cox regression analyses assessed factors associated with metastasis. We tested the hypothesis that the impact of ADT varied according to the risk of metastasis. An interaction with groups (concomitant ADT vs no ADT) and the probability of distant metastasis according to a newly developed model was tested. A nonparametric curve explored the relationship between the risk of metastasis and 10-yr metastasis rates according to ADT. Results and limitations: Median PSA and radiotherapy dose were 0.42 ng/ml and 66 Gy, respectively. Overall, 178 (34%) patients received ADT. At a median follow-up of 104 mo, 71 patients experienced metastasis. Grade group ≥4 (hazard ratio [HR]: 1.66; 95% confidence interval [CI]: 1.01–3.30), pT3b/4 (HR: 2.61; 95% CI: 1.51–4.52), and dose (HR: 0.82; 95% CI: 0.76–0.89) were associated with metastasis. The impact of ADT differed according to the risk of metastasis calculated using a multivariable model (p = 0.01). This was confirmed when considering patients treated with early SRT (p = 0.046), where ADT was associated with a reduction in the rate of metastasis only in eSRT; patients with more aggressive characteristics (ie, pT3b/4 and grade group ≥4, or pT3b/4 and PSA at eSRT ≥0.4 ng/ml). Conclusions: The beneficial effect of ADT concomitant to eSRT varied significantly according to disease characteristics, such that only men with more aggressive PCa features benefit from ADT in the eSRT setting for BCR after RP. Patient summary: The oncological benefits of concomitant androgen deprivation therapy (ADT) in patients undergoing salvage radiotherapy (SRT) vary according to pathological characteristics. Only patients with more aggressive disease characteristics seemed to benefit from the use of hormonal manipulation at the time of early SRT. Conversely, the potential side effects of ADT could be spared in patients with low prostate-specific antigen levels and favorable pathological features. Concomitant androgen deprivation therapy at the time of early salvage radiotherapy has been shown to improve 10-yr metastasis-free survival only in patients with more aggressive disease characteristics.
AB - Background: Hormonal manipulation concomitant to salvage radiotherapy (SRT) given for biochemical recurrence (BCR) after radical prostatectomy (RP) improved outcomes in two randomized trials. However, neither of these studies focused on men treated at low prostate-specific antigen (PSA) levels. Objective: To test if the impact of androgen deprivation therapy (ADT) on metastasis in patients undergoing early SRT varies according to prostate cancer (PCa) features. Design, setting, and participants: A total of 525 patients received SRT at PSA levels ≤2 ng/ml. Outcome measurements and statistical analyses: Multivariable Cox regression analyses assessed factors associated with metastasis. We tested the hypothesis that the impact of ADT varied according to the risk of metastasis. An interaction with groups (concomitant ADT vs no ADT) and the probability of distant metastasis according to a newly developed model was tested. A nonparametric curve explored the relationship between the risk of metastasis and 10-yr metastasis rates according to ADT. Results and limitations: Median PSA and radiotherapy dose were 0.42 ng/ml and 66 Gy, respectively. Overall, 178 (34%) patients received ADT. At a median follow-up of 104 mo, 71 patients experienced metastasis. Grade group ≥4 (hazard ratio [HR]: 1.66; 95% confidence interval [CI]: 1.01–3.30), pT3b/4 (HR: 2.61; 95% CI: 1.51–4.52), and dose (HR: 0.82; 95% CI: 0.76–0.89) were associated with metastasis. The impact of ADT differed according to the risk of metastasis calculated using a multivariable model (p = 0.01). This was confirmed when considering patients treated with early SRT (p = 0.046), where ADT was associated with a reduction in the rate of metastasis only in eSRT; patients with more aggressive characteristics (ie, pT3b/4 and grade group ≥4, or pT3b/4 and PSA at eSRT ≥0.4 ng/ml). Conclusions: The beneficial effect of ADT concomitant to eSRT varied significantly according to disease characteristics, such that only men with more aggressive PCa features benefit from ADT in the eSRT setting for BCR after RP. Patient summary: The oncological benefits of concomitant androgen deprivation therapy (ADT) in patients undergoing salvage radiotherapy (SRT) vary according to pathological characteristics. Only patients with more aggressive disease characteristics seemed to benefit from the use of hormonal manipulation at the time of early SRT. Conversely, the potential side effects of ADT could be spared in patients with low prostate-specific antigen levels and favorable pathological features. Concomitant androgen deprivation therapy at the time of early salvage radiotherapy has been shown to improve 10-yr metastasis-free survival only in patients with more aggressive disease characteristics.
KW - Androgen deprivation therapy
KW - Prostate cancer
KW - Radical prostatectomy
KW - Salvage radiotherapy
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U2 - 10.1016/j.eururo.2017.11.020
DO - 10.1016/j.eururo.2017.11.020
M3 - Article
C2 - 29229176
AN - SCOPUS:85043576589
SN - 0302-2838
VL - 73
SP - 512
EP - 518
JO - European urology
JF - European urology
IS - 4
ER -