MATERIALS AND METHODS

A retrospective review of all hypogonadal men with a history of CaP

treated with either brachytherapy or EBRT (collectively referred to as

‘radiation treatment’) who subsequently received TRT at Baylor College

of Medicine was performed after Institutional Review Board approval; 17

men were identiFed, 4 of whom were excluded owing to lack of available

prostate biopsy data or baseline PSA values. All men underwent radiation

treatment for CaP between 1994 and 2009 and TRT was initiated

between 2006 and 2010. The diagnosis of hypogonadism was based on

the presence of symptoms, including low libido, erectile dysfunction, low

energy, poor concentration, inadvertent weight gain and sleep distur-

bances, as well as serum T

300 ng dl

. Initial TRT consisted of a trans-

dermal T formulation in 12 patients and subcutaneous T pellets in

1 patient. ±our patients were placed on androgen deprivation therapy

(ADT) prior to starting radiation treatment, one of whom was diagnosed

with high-grade disease. Men were also risk-stratiFed using the National

Comprehensive Cancer Network (NCCN) guidelines and 4, 7 and 2 patients

were found to be at very low or low, intermediate, or high risk for CaP

recurrence, respectively.

Baseline serum T, free T (±T), hemoglobin (Hgb), hematocrit (Hct),

estrogen (E), sex hormone-binding globulin (SHBG) and PSA levels were

determined after completion of EBRT or placement of brachytherapy

seeds, but before initiation of TRT. Subsequent hormonal evaluation was

performed approximately every 3 months after TRT initiation. PSA velocity

(PSAV) was calculated using linear regression of three or more serum PSA

values obtained over at least a 12-month period. Of note, PSAV was not

determined for one patient, as only two PSA values were available and

these were within 5 months of each other. The majority of serum hormone

evaluations were performed by the Laboratory for Male Reproductive

Research and Testing at Baylor College of Medicine on a single Beckman

Coulter Access2 assay system (Beckman Coulter, Brea, CA, USA), with a

minority of samples analyzed by outside laboratories. Subjective improve-

ment in libido, erections and energy was assessed using direct questioning

of patients prior to initiation of TRT and during follow-up.

Data were analyzed using Microsoft OfFce Excel (Microsoft, Redmond,

WA, USA) and SPSS (IBM Corporation, Somers, NY, USA). Statistical com-

parisons between baseline and follow-up values were performed using

the Wilcoxon rank-sum test, with a

-value

0.05 considered statistically

signiFcant.

RESULTS

Thirteen hypogonadal patients with a history of CaP were treated

with TRT after completion of radiation treatment (Table 1). The

median time to initiation of TRT after radiation treatment was 13.5

months, and the time from initiation of radiation treatment to last

follow-up PSA was 45.6 months. The median age at TRT initiation

was 68.0 years. Prostate biopsy results evidenced four patients

with Gleason (Gl) 6, 7 with Gl 7 and 2 with Gl 8 disease, with no

men having evidence of locally advanced CaP. Using the NCCN

guidelines to risk stratify our cohort, we found 4, 7 and 2 patients

to be at very low or low, intermediate, or high risk for CaP

recurrence, respectively. Of the 13 patients in the cohort, 3 were

treated with brachytherapy and 10 with EBRT. ±our patients

received ADT in addition to radiation treatment for PSA levels of

1.9, 14, 15 and 18 ng ml

and Gl 4

7, 4

7, 3

and 4

8 disease, respectively. Three patients were started on

TRT prior to being diagnosed with CaP and TRT was restarted after

CaP treatment.

The median follow-up period after TRT initiation was 29.7

months (range 2.3–67.3 months). Baseline median (interquartile

range) serum values were: T 178.0 (88.0–263.5) ng dl

, ±T 5.1

(3.6–5.8) pg ml

, E 18.0 (11.0–35.0) pg ml

, SHBG 31.5 (19.3–

36.5) nmol l

and PSA 0.30 (0.06–0.95) ng ml

. Median serum T

was signiFcantly higher after TRT initiation compared with

baseline throughout the duration of follow-up, except for the

time periods of 18–24 and

30 months (Table 2). No signiFcant

increases from baseline ±T or E were observed during follow-up.

There was an overall increase in the mean SHBG during the course

of treatment with signiFcance reached at 18–24 months follow-up

(38.5 (34.3–56.3) nmol l

0.042).

Median PSA in the cohort was 0.30 (42.8–49.0) ng ml

baseline and 0.66 (0.16–1.35) ng ml

at median follow-up

(

0.345). No signiFcant changes in PSA were observed during

the follow-up period of up to 67.3 months (Table 2). The median

difference between baseline and PSA at median follow-up was

0.055 ng ml

and the median PSAV within the cohort was

0.004

(

0.080 to 0.010) ng ml

per year. Biochemical recurrence was

suspected in one patient with Gl 4

8 disease who had been

treated with brachytherapy as well as ADT. This patient had a pre-

radiation treatment PSA of 18 ng ml

, a pre-TRT PSA of

0.009 ng ml

, with a nadir of 0.002 ng ml

after starting TRT, which

subsequently rose to 1.82 ng ml

with a PSAV of 0.93 ng ml

per year, prompting cessation of TRT and workup for CaP recur-

rence. Repeat prostate biopsy, computed tomography and bone

scans showed no evidence of cancer, at which point the patient

resumed TRT. His PSA has since remained stable at 1.31 ng ml

on TRT. The second patient who received ADT in addition

to radiation treatment had a pre-radiation treatment PSA of

15 ng ml

, a baseline PSA of 0.4 ng ml

prior to TRT initiation,

and a maximum PSA of 1.29 ng ml

while on TRT, which sub-

sequently decreased to 0.629 ng ml

during treatment. TRT was

not stopped at any point during this patient’s follow-up. The third

patient who received ADT had a pre-radiation treatment PSA of

14 ng ml

while on TRT, a maximum PSA of 0.30 ng ml

while

on TRT, with stable PSA and no evidence of recurrence. ±inally, the

fourth patient who received ADT had a pre-radiation treatment

PSA of 1.9 ng ml

, a baseline PSA of 0.09 ng ml

prior to TRT

initiation, a maximum PSA of 0.1 ng ml

during treatment, with

transient cessation of TRT due to supraphysiological T levels.

A side effect of exogenous T administration is the development

of erythrocytosis. In our cohort, only three patients had baseline

Hgb and Hct values available and, as a result, we were unable to

make direct comparisons between baseline and follow-up Hgb

and Hct. However, the maximum Hgb and Hct in any single

Table 1.

Patient Demographics

Pre-radiation treatment PSA, median (IQR),

ng ml

(

)

5.8 (3.0–14.0), (9)

Prostate biopsy Gleason sum (

(%))

Gleason 6

4 (31%)

Gleason 7

7 (54%)

Gleason 8

2 (15%)

Comorbidities (

(%))

Diabetes mellitus

2 (15%)

Hypertension

5 (38%)

Hyperlipidemia

3 (23%)

Coronary artery disease

3 (23%)

Smoking (previous or current)

5 (38%)

Post-radiotherapy erectile dysfunction

9 (69%)

Cancer Treatment (

(%))

Brachytherapy

3 (23%)

EBRT

10 (77%)

Radiotherapy

ADT

4 (31%)

Age at TRT initiation (years), median (IQR)

68.0 (62.0–77.0)

Months between XRT completion and TRT

initiation, median (range)

13.5 (2.6–170.9)

Months between XRT completion and last

follow-up PSA, median (range)

45.6 (11.7–219.8)

Months between TRT initiation and last follow-

up PSA, median (range)

29.7 (2.3–67.3)

Abbreviations: ADT, androgen deprivation therapy; EBRT, external beam

radiotherapy; IQR, interquartile range; PSA, prostate-speciFc antigen;

TRT, testosterone replacement therapy; XRT, radiation therapy.

Testosterone replacement after radiation treatment for prostate cancer

AW Pastuszak

et al

2013 Macmillan Publishers Limited

International Journal of Impotence Research (2013), 24 – 28