Normalization of serum testosterone levels in patients treated with neoadjuvant hormonal therapy and three-dimensional conformal radiotherapy for prostate cancer.
OBJECTIVE
To determine the expected time to serum testosterone normalization after short-course neoadjuvant androgen deprivation therapy (NAAD) and three-dimensional conformal radiotherapy for patients with localized prostate cancer and to identify pretreatment predictors that correlated with the time to testosterone normalization.


METHODS
Between 1993 and 1999, 88 patients with localized prostate cancer, treated with NAAD and external beam radiotherapy, were prospectively monitored after treatment with sequential testosterone levels. NAAD was administered before and during the entire course of radiotherapy and discontinued at the end of treatment. The median duration of NAAD was 6 months. The actuarial rate of serum testosterone normalization from the end of treatment was evaluated, and the presence or absence of androgen deprivation-related symptoms was correlated with serum testosterone levels. Symptoms assessed included weight gain, loss of libido, breast tenderness, breast enlargement, hot flashes, and fatigue.


RESULTS
Serum testosterone levels returned to the normal range in 57 (65%) of the 88 patients and failed to normalize in 31 patients (35%). The median time to normalization was 18.3 months. The actuarial rate of normalization at 3, 6, 12, and 24 months was 10%, 26%, 38%, and 59%, respectively. In a multivariate analysis, a pretreatment testosterone level in the lower range of normal was the only variable that predicted for delayed testosterone normalization after NAAD (p = 0.00047). Among 45 patients with information concerning androgen deprivation-related symptoms recorded 1 year after cessation of NAAD, 24 (53%) had normalized testosterone levels, but in 21 patients (47%), the levels had not yet returned to normal. At 1 year, only 1 (4%) of 24 patients whose testosterone level had returned to normal experienced NAAD-related symptoms compared with 14 (67%) of 21 patients who did not have normal testosterone levels (p <0.001).


CONCLUSIONS
Testosterone levels often remain depressed for extended periods after cessation of short-course NAAD. Lower baseline testosterone levels predict for a delay in testosterone normalization, and the persistence of symptoms related to androgen deprivation correlates with low testosterone levels.
Padula
Gilbert D A
GD
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Zelefsky
Michael J
MJ
Venkatraman
Ennapadam S
ES
Fuks
Zvi
Z
Lee
Henry J
HJ
Natale
Linda
L
Leibel
Steven A
SA
D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage; D008297:Male; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009570:Nitriles; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000628:therapy*; D020266:Radiotherapy, Conformal / Q000379:methods*; D012016:Reference Values; D012044:Regression Analysis; D013739:Testosterone / Q000097:blood*; D013997:Time Factors; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; D013739:Testosterone; C053541:bicalutamide; D016729:Leuprolide