Kinetics of testosterone recovery in clinically localized prostate cancer patients treated with radical prostatectomy and subsequent short-term adjuvant androgen deprivation therapy

Abstract

Androgen deprivation therapy (ADT) is a standard treatment for metastatic, recurrent and locally advanced prostate cancer (PCa). The aim of this study is to investigate the timing and extent of testosterone recovery in clinically localized PCa patients treated with radical prostatectomy (RP) and subsequent short-term adjuvant ADT. A total of 95 localized PCa patients underwent RP and 9-month adjuvant ADT were included in this prospective study. Serum testosterone level was measured before adjuvant ADT, at ADT cessation, and at 1, 3, 6, 9 and 12 months after cessation of ADT. A Cox proportional hazards model was used to assess variables associated with the time of testosterone normalization. The results showed that median patient age was 67 years and median testosterone level before adjuvant ADT was 361 (230-905) ng dl 21 . All patients finished 9-month adjuvant ADT and achieved castrate testosterone level. At 3 months after ADT cessation, testosterone recovered to supracastrate level in 97.9% patients and to normal level in 36.9% patients. The percentage of patients who recovered to normal testosterone level increased to 66.3%, 86.3% and 92.6% at 6, 9 and 12 months, respectively. Cox regression model found that higher baseline testosterone level (o300 ng dl 21 ) was the only variable associated with a shorter time to testosterone normalization (hazard ratio: 1.98; P 5 0.012). In conclusion, in most patients, testosterone recovered to supracastrate level at 3 months and to normal level at 12 months after 9-month adjuvant ADT cessation. Patients with higher baseline testosterone level need shorter time of testosterone normalization.

Negative impact of neoadjuvant hormonal therapy on detecting biochemical recurrence after radical prostatectomy

“…Therefore, an increase in postoperative patients with NHT is of concern in the near future and the establishment of an optimal follow-up schedule for NHT patients is an urgent issue. Several previous studies examined the time course and extent of testosterone recovery after the discontinuation of androgen deprivation therapy [16][17][18][19][20][21][22][23]. In half of the patients, the testosterone level recovered to a supracastrate level around 1 year after cessation of hormonal therapy, but it took an additional 1-12 months to recover to a baseline level [16][17][18][19][20][21][22][23].…”

“…Several previous studies examined the time course and extent of testosterone recovery after the discontinuation of androgen deprivation therapy [16][17][18][19][20][21][22][23]. In half of the patients, the testosterone level recovered to a supracastrate level around 1 year after cessation of hormonal therapy, but it took an additional 1-12 months to recover to a baseline level [16][17][18][19][20][21][22][23]. Furthermore, delayed testosterone recovery is significantly associated with high age [16,[18][19][20][21][22], hypertension [21], diabetes [22], low baseline testosterone level [16,18,[20][21][22], low serum sex hormone-binding globulin level [21], and the long duration of hormonal therapy [18][19][20][21][22].…”

“…For NHT, a luteinizing hormone releasing hormone (LHRH) agonist/antagonist and/or antiandrogen drug are usually selected. Several previous studies demonstrated that testosterone recovery to the normal level after hormonal therapy took several months [16][17][18][19][20][21][22][23]. On the other hand, the duration that NHT affects the pattern of BCR after RP has not been examined.…”

<p>miR-135b-5p Suppresses Androgen Receptor-Enhanced Hepatocellular Carcinoma Cell Proliferation via Regulating the HIF-2α/c-Myc/P27 Signals in vitro</p>

“…25 However, Dai et al found that ADT failed to yield fruitful results. 26 Instead of using anti-androgens to prevent androgen binding to AR, Ma et al 27 and Wu et al 28 applied the AR degradation enhancer ASC-J9 to directly target AR to suppress HCC progression. The experiments reported in this manuscript further support the notion that AR can increase the proliferation of HCC promoting its progression.…”

Unsafe testosterone-based dosing regimen of androgen deprivation therapy in patients with locally advanced or metastatic prostate cancer: a prematurely ended randomized controlled trial (MIDAS-trial)

“…Our results show that the testosterone concentration stays longer below the castrate level as described in current literature. Dai et al showed that, in LHRH-agonist naïve patients, 1 and 3 month(s) after cessation of monthly injections of goserelin acetate 3.6 mg or triptorelin acetate 3.75 mg, testosterone recovered to supracastrate level in 43.2% and 97.9% of the patients [18]. Furthermore, Gulley et al found that, in LHRH-agonist naïve patients, after 6 months of injections of leuprolide 22.5 mg and goserelin 10.8 mg, more than 80% of the patients achieved supracastrate serum testosterone level by 15 weeks.…”