Nadir Testosterone after Long-Term Followup Predicts Prognosis in Patients with Prostate Cancer Treated with Combined Androgen Blockade

Abstract

Nadir testosterone 20 ng/dl was the most significant cutoff level for overall survival in Japanese patients with prostate cancer treated with combined androgen blockade.

Maximal testosterone suppression in the management of recurrent and metastatic prostate cancer

“…31 A multicentre study analyzed data from 225 patients receiving complete androgen blockade with an LHRH agonist or antagonist, or surgical castration plus antiandrogens for localized, locally advanced, or metastatic PCa. 26 The data demonstrated improved outcomes for patients with testosterone levels <0.7 nmol/l compared with those with testosterone ≥0.7 nmol/l. Median PFS was 16.3 vs. 11.0 months (p=0.1163), while median OS was 68.3 vs. 28.3 months (p<0.0014), respectively.…”

“…[21][22][23]27,29 Four of six retrospective studies of localized, locally advanced, or metastatic PCa also demonstrated improved outcomes (lower rates of testosterone breakthrough, PFS, CSS, or OS) for patients achieving testosterone suppression ≤0.7 nmol/l or ≤1.1 nmol/l compared to those with serum testosterone levels >0.7 nmol/l or >1.1 nmol/l, respectively. 26,28,30,31 A similar trend was seen in a recent post-hoc analysis of the ICELAND study, which demonstrated an association between lower nadir testosterone level and a trend toward longer time to PSA (CRPC) progression (≤0.7 nmol/l vs. >0.7 nmol/l to ≤1.7 nmol/l; HR 5.06; 95% CI 1.3-16.1; p=0.062; at the time of publication, the ICELAND study report was only available in abstract form). 32 Overall, these data provide compelling support for a relationship between low testosterone levels and improved outcomes.…”

“…Among the 11 trials reviewed, nine reported survival-related outcomes for patients with testosterone levels ranging from ≤0.1 nmol/l to <1.1 nmol/l, 21,22,24,[26][27][28][29][30] eight of which showed significant improvements in these outcomes. A single retrospective study observed a significant improvement in OS with testosterone levels of ≤0.1 nmol/l compared with levels >0.1 nmol/l; p=0.014) 24 and two studies, one prospective 22 and one retrospective, 30 showed significant improvements in PFS-related outcomes (time to CRPC, p=0.05 and survival free of androgen-independent progression, p<0.03, respectively) at testosterone levels <1.1 nmol/l compared with >1.1 nmol/l.…”

“…Median PFS was 16.3 vs. 11.0 months (p=0.1163), while median OS was 68.3 vs. 28.3 months (p<0.0014), respectively. 26 Additional univariate analyses showed that significantly improved OS outcomes were limited to low testosterone levels of <0.6 nmol/l (p=0.0190), <0.7 nmol/l (p=0.0020), and <1.1 nmol/l (p=0.0146), but not associated with very low testosterone levels <0.3 nmol/l and <0.4 nmol/l.…”

“…26,28,30,31 The largest study (n=2196) analyzed testosterone breakthrough data for patients receiving adjuvant LHRHA therapy following curative radiotherapy. 31 Lower rates of testosterone breakthrough (increase in serum testosterone >0.7 nmol/l during ADT) were associated with improved PSA kinetics, an indicator of disease control.…”