using TTh in men with CaP. These results confrm

prior reports oF a low rate oF recurrent CaP in men

who receive TTh.

We observed a slight increase in PSA in men on

TTh with high risk CaP, consistent with prior

studies showing slight increases in PSA For several

months aFter TTh initiation in hypogonadal men. In

a randomized, controlled trial oF TTh in 44 men

Marks et al noted this PSA increase in the treatment

and placebo groups.

In a study oF 75 hypogonadal

men with or without PIN treated with TTh slight

PSA increases were observed in the PIN positive and

negative groups with only 1 CaP case Found in the

PIN positive group aFter 1 year oF TTh.

Supplementary

table

(http://jurology.com/

)

shows the literature on TTh in men with CaP.

Previous studies oF the eFfcacy and saFety oF TTh

aFter RT For CaP in a total oF 69 men demonstrated

no BCR and no PSA increases.

In 2007 Sarosdy

evaluated 31 men with CaP treated with brachy-

therapy Followed by TTh.

There was a transient

increase in PSA in 1 patient during a median oF

5 years. Subsequently Morales et al evaluated 5

hypogonadal men with localized CaP treated with

EBRT and TTh, and also Found a transient increase

in PSA in 1.

Pastuszak et al evaluated a cohort oF

13 men with localized CaP treated with EBRT or

brachytherapy and TTh.

The men were Followed a

median oF 2.5 years and only 1 had a transient PSA

increase. In 2014 Balbontin et al reported a series oF

20 men with CaP treated with brachytherapy Fol-

lowed by TTh who were Followed a median oF 2.5

years.

They observed a decrease in PSA in the

cohort From 0.07 to 0.01 ng/ml.

Studies in men treated with RP have similarly

demonstrated low rates oF CaP recurrence or pro-

gression with minimal changes in mean PSA at

Followup as long as 12 years.

A retrospective re-

view oF 103 hypogonadal men on TTh and 49 non-

hypogonadal men with a history oF CaP treated with

RP showed a small, statistically signifcant increase

in PSA in the hypogonadal cohort on TTh.

There

was lower BCR in that group during the 28-month

Followup compared with that in an untreated com-

parison group. Overall in men treated with RP the

existing literature reveals that CaP recurrences

were reported in only 4 oF 177 patients (2%)

(supplementary table 2, http://jurology.com/

). This

value is lower than published rates oF 6% to 9%

3 years aFter RP and 14% at 5 years.

4,5,7,16

addition, even in a study oF 13 hypogonadal men

with CaP who were on TTh and active surveillance

no clinical progression was observed during a me-

dian 2.5 years oF Followup.

In our cohort 6 oF 98 (6%) men met BCR criteria.

Notably 3 men with suspected BCR originally un-

derwent brachytherapy with PSA peaking and

subsequently decreasing (table 2). Rather than

representing BCR, this may have been a post-

brachytherapy PSA bounce and was unlikely to be

a direct eFFect oF TTh. When examining outcomes in

the high risk subgroup, 2 oF 11 men (18.2%) met

BCR criteria. Previously reported CaP recurrence

rates Following RT in men who did not undergo TTh

range From 13% to 65% with high risk disease in less

than 10% oF these cohorts.

17,18

ZeleFsky et al Found

that For tumors treated with conFormal radiation

5-year BCR was 35% to 65% among men with a

Gleason sum oF greater than 6 depending on tumor

stage and baseline PSA.

Similarly ±ukunaga-

Johnson et al reported 66% 5-year BCR aFter RT

in patients with Gl 8-10 disease and 40% BCR

2 years aFter RT.

It is reassuring that rates oF CaP

recurrence in the current study were lower than

reported recurrence rates aFter RT without TTh.

However, we cannot draw defnitive conclusions on

the saFety oF TTh in this setting due to the study

limited sample size, retrospective nature, overall

short Followup and absent eugonadal control group.

The long-standing concern regarding TTh in men

with CaP originated with the seminal 1941 study oF

Huggins and Hodges, which demonstrated regres-

sion oF metastatic CaP Following castration or es-

trogen administration.

This led to the androgen

dependent model oF CaP. Although it has been

interpreted to suggest that increasing serum T is

deleterious, this view is not supported by modern

evidence. In a large prospective study in 3,886 men

with CaP and 6,448 age matched controls the CaP

risk was unrelated to the serum androgen concen-

tration.

In the placebo arm oF the REDUCE

(Reduction by Dutasteride oF Prostate Cancer

Events) trial in 3,255 men in which participants

underwent prostate biopsies at years 2 and 4 the

CaP risk was also unrelated to the serum T or

dihydrotestosterone concentration.

In a meta-

analysis oF 22 randomized, placebo controlled tri-

als in a total oF 2,351 men who were studied up to

36 months the group on T were at no greater risk For

CaP than the men on placebo.

The apparent paradox between the prostate eF-

Fects oF ADT and the Failure to identiFy an increased

CaP risk in men with higher serum androgens is

explained by the saturation model, which describes

a fnite ability oF androgens to stimulate CaP

growth.

The saturation point appears to be

approximately 250 ng/dl based on evidence From the

TriUS (Testim

Registry in the United States)

trial

and a placebo controlled study oF T gel.

each study PSA increases were Found in men with

baseline T less than 250 ng/dl but not in men with T

greater than 250 ng/dl. A saturation curve was

similarly Found by Rastrelli et al in their population

oF 2,967 men in whom maximal PSA was achieved at

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TESTOSTERONE THERAPY AFTER RADIATION THERAPY FOR PROSTATE CANCER