YPOGONADISM

, which is diagnosed in approximately

500,000 men annually in the United States, shows

an increasing incidence with age and is character-

ized by low serum T and symptoms including loss of

libido, erectile dysfunction, depression, lethargy,

concentration difFculties, sleep disturbances, osteo-

porosis and loss of muscle mass.

TTh ameliorates

these symptoms in most men. Hypogonadism most

commonly affects middle-aged or older men, a pop-

ulation that is also frequently affected by CaP.

Thus, these conditions often coexist, especially as

RT for CaP is associated with lower serum T.

However,

TTh

has

historically

been

contra-

indicated in men with CaP due to concern that

higher serum T would enhance CaP growth.

Recent clinical experiences have suggested that

TTh is not as risky as once believed in men with

CaP. In multiple series in which TTh was offered to

men following RP 4 CaP recurrences were observed

among 177 cases.

However, the safety of TTh in

men after RT for CaP is more uncertain, in part due

to the small number of reported cases. ±urthermore,

TTh in men with CaP following RT may appear

more risky than after RP, in part due to the chance

of residual CaP after RT, the unknown status of

lymph nodes or surgical margins and absent pa-

thology data on the entire prostate gland. However,

several small studies in a total of 69 patients with

CaP treated with TTh following brachytherapy and/

or EBRT have revealed transient increases in PSA

but no CaP recurrence or progression.

In addi-

tion, in men with CaP on active surveillance no

signiFcant increases in PSA or CaP progression

have been observed.

We present our multi-institutional experience of

the effects of TTh on longitudinal CaP outcomes in

hypogonadal men after RT.

MATERIALS AND METHODS

Patient Identifcation and Data Acquisition

We retrospectively reviewed the records of men with

hypogonadism treated with TTh after RT for CaP at a

total of 4 institutions, including Baylor College of Medi-

cine, Men’s Health Boston, University of South ±lorida,

and South Texas Urology and Urologic Oncology. Insti-

tutional review board approval was obtained from all

participating institutions and data sharing agreements

were put in place. RT encompassed EBRT and brachy-

therapy with men in the cohort undergoing EBRT and/or

brachytherapy. Patients underwent RT for CaP from 1994

to 2012 and received TTh between 1999 and 2013. Men

were diagnosed with hypogonadism by hypogonadal

symptoms, including low libido, erectile dysfunction and

fatigue, as well as by biochemical Fndings, including

serum T 350 ng/dl or less, and/or ±T less than 1.5 ng/dl or

calculated ±T less than 100 pg/ml. Patients received TTh

via gel, injection or subcutaneously implanted pellets.

Baseline serum T, ±T, estradiol, sex-hormone binding

globulin and PSA were determined before TTh initiation.

±ollowup serum hormone values were evaluated every

3 to 6 months thereafter. All followup serum values

presented correspond to the most recent value available.

±ollowup represents the time from initial presentation

through the most recent followup. Laboratory testing was

performed at the Laboratory for Male Reproductive

Research and Testing, Baylor College of Medicine (LIL

and MK); Tosoh Bioscience, San ±rancisco, California

(AM); LabCorp, Burlington, North Carolina (M±S); or

Quest Diagnostics, Madison, New Jersey (AM and RC).

Men were grouped into risk subgroups, including

low

Gl 6 or less, intermediate

Gl 3

4 and 4

3, and

high

Gl 8 or greater. BCR was deemed to have occurred

if any of certain conditions were met, including 1) PSA

greater than absolute nadir plus 2 ng/ml, 2) PSA greater

than current nadir plus 3 ng/ml or 3) 2 consecutive in-

creases in PSA of 0.5 ng/ml or greater.

Current nadir

was deFned as the lowest PSA before the elevated PSA

concerning for BCR. Absolute nadir referred to the lowest

PSA during followup.

Statistical Analysis

Baseline and followup serum values were compared using

the Wilcoxon signed rank test. PSAV was calculated by

linear regression using at least 3 PSA values during

12 months or greater. PSAV was compared across sub-

groups with the Kruskal-Wallis and ±isher exact tests. All

analyses were performed using SPSS

, version 21 with

0.05 considered signiFcant.

RESULTS

We identiFed 98 hypogonadal men with a history of

CaP who underwent RT and were subsequently

started on TTh (supplementary table 1, http://

jurology.com/

). Median age was 70.0 years (range

34 to 85). Of the men 50 (51%) received ADT in

addition to RT for initial CaP management while

the remainder received RT alone. The interval be-

tween ADT cessation and TTh initiation was 5 to

60 months. No individual was receiving ADT at the

time of TTh initiation.

Initial prostate biopsy data were available on 86

men

(87.8%),

including

(3.1%)

with

44 (44.9%) with Gl 6, 28 (28.6%) with Gl 7, 7 (7.1%)

with Gl 8 and 4 (4.1%) with Gl 9 disease. TTh was

started a median of 28.6 months (range 13.8 to 40.4)

after RT. The mode of TTh was gels in 65%, in-

jections in 24% and pellets in 11%. The median time

from TTh initiation to the most recent followup visit

was 40.8 months (range 1.5 to 147).

Table 1 lists baseline and followup results. Median

serum T increased from 209 to 420 ng/dl (p

0.001)

and median free T increased from 5.9 to 10.7 pg/ml

0.001) at followup. Median serum PSA was 0.08

ng/ml at baseline and 0.09 ng/ml at followup

0.05). Serum estradiol and sex-hormone binding

globulin did not change signiFcantly.

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TESTOSTERONE THERAPY AFTER RADIATION THERAPY FOR PROSTATE CANCER