Treatment for Locally Advanced Prostate Cancer (T3, T4)

534

Practical Urology: EssEntial PrinciPlEs and PracticE

with androgen-deprivation therapy, and radical

prostate tissue remains. The AUA Prostate

prostatectomy.

Cancer Guidelines panel systematic review

noted significant variability in definitions of

EBRT with ADT

biochemical recurrence following radical pros-

tatectomy, but endorsed the standard of PSA

The physiologic

rationale

for

combining

>0.2 ng/mL as representing biochemical failure,

although not necessarily a threshold to initiate

androgen-deprivation therapy with radiation

therapy.39 Many clini-

therapy is a potentially synergistic effect on

cians regard a PSA level >0.4 ng/mL following

prostate cancer

cells. Androgen deprivation

radical prostatectomy as an indication for inter-

likely increases

apoptosis in

the

irradiated

vention (ADT), following appropriate staging

field, and may also delay or prevent the devel-

evaluations. Tumor grade, time to PSA recur-

opment of metastatic disease. Clinical support

rence after surgery, and PSA doubling time are

for these hypotheses is provided by the results

associated with the risk of prostate cancer mor-

of two randomized controlled trials (RTOG

tality, and may be used to risk stratify those

85–10 and EORTC), which suggests that imme-

patients who may potentially benefit from early

diate ADT with EBRT results in better out-

a biochemical recur-

comes than EBRT

alone, among

men with

rence.40 A large, retrospective cohort study dem-

locally advanced or high-risk prostate cancer.

onstrated

reduced

incidence

of

metastatic

Furthermore, secondary analyses of additional

disease among high-risk (Gleason sum >7 or

trials (i.e., RTOG

85–31) suggest

that early

PSADT <12 months) men initiated on ADT for

indefinite ADT improves outcomes as com-

PSA recurrence following radical

prostatec-

pared with EBRT alone.

tomy.41,42 However, definitive data regarding the

Radical Prostatectomy

benefit of early versus delayed androgen depri-

vation in this setting is lacking. Men with short

Radical prostatectomy, with or without ADT, is a

PSA doubling times (<15 months) appear to be

at higher risk for disease-specific

mortality.

43

reasonable option

for locally

advanced (T3)

Randomized trials are needed in this area to

prostate cancer. Well-differentiated T3 prostate

further define the role of ADT for PSA recur-

cancers have a disease-specific survival follow-

rence among men at higher risk for prostate

ing radical prostatectomy of approximately 76%.

cancer death.

Androgen-deprivation therapy may improve

outcomes following radical prostatectomy in

this group, although further research is required

PSA Recurrence Following Radiation

to clearly define the role of androgen depriva-

Therapy

tion for locally advanced disease following radi-

cal prostatectomy.

The 1996 consensus definition for PSA recur-

rence following radiation therapy is three con-

Treatment for Recurrence

secutive increases in PSA, with the time of

failure defined as halfway between the first rise

Following Definitive Local

in PSA and the prior measurement.As with PSA

recurrence

following

radical

prostatectomy,

Therapy

rapidly rising PSA

is

a harbinger of more

aggressive disease and shorter time to distant

PSA Recurrence Following Radical

metastasis. Androgen-deprivation therapy is

most commonly used to treat PSA recurrence

Prostatectomy

following radiation therapy. Salvage surgery has

a very high complication rate, and a significant

Undetectable PSA levels are expected following

risk of incontinence, and is therefore rarely per-

radical prostatectomy, thus PSA is potentially a

formed. Cryotherapy of the prostate is a rela-

very sensitive marker for disease recurrence.

tively new option to treat postradiation PSA

However, some patients may develop very low

recurrence, so long-term data on outcomes is

levels of PSA following prostatectomy if benign

lacking.