EURURO Vol. 71 No. 4

632 692

RT has shown benefit in terms of biochemical progression-
free survival (PFS) after 5 yr in retrospective series and
in PFS for ‘‘high-risk’’ tumours , and recent data from
RTOG 9601 suggested both cancer-specific survival
(CSS) and OS benefits for adding 2 yr of bicalutamide to SRT.
According to GETUG-AFU 16, also short-term application of
a GnRH-analogue (6 mo) can significantly improve 5 yr PFS
after SRT ).
A large retrospective case-matching study evaluated
adjuvant RT (ART) versus early SRT and included pT3N0 R0/
R1 patients only (ADT was excluded); 390 of 500 patients
receiving observation plus early SRT (median pre-SRT PSA
was 0.2 ng/ml) were propensity matched with 390 patients
receiving ART. At 2 and 5 yr after surgery, rates for no
evidence of disease (NED) were 91% and 78%, respectively,
for ART compared with 93% and 82%, respectively, after SRT.
Subgroup analyses did not yield significant differences for
the two approaches. It was concluded that early SRT does
not impair PCa control but clearly helps reduce overtreat-
ment, which is a major issue in ART .
2.4. Management of prostate-specific antigen relapse following
radiation therapy
Salvage RP (SRP) is most likely to achieve local control. In a
recent systematic review , SRP was shown to provide 5-
and 10-yr BCR-free survival (BCR-FS) estimates ranging
from 47% to 82% and from 28% to 53%, respectively. The 10-
yr CSS and OS rates ranged from 70% to 83% and from 54% to
89%, respectively. SRP is associated with increased morbid-
ity (anastomotic stricture rate 30%, rectal injury 2%) and
high levels of incontinence and erectile dysfunction (ED)
. SRP should be considered only for patients with low
comorbidity, life expectancy of at least 10 yr, a pre-SRT PSA
level <10 ng/ml and biopsy Gleason score 7, no lymph
node involvement before SRT, and initial clinical stage of T1
or T2.
Salvage cryoablation of the prostate (SCAP) has been
proposed as an alternative to SRP. In a review of the use of
SCAP for recurrent cancer after RT, the 5-yr biochemical
disease-free survival estimates ranged from 50% to 70%. A
durable response can be achieved in approximately 50% of
patients with a pre-SCAP PSA level <10 ng/ml . In a
multicentre study reporting the current outcome of SCAP in
279 patients, the 5-yr BCR-FS estimate according to the
Phoenix criteria was 54.5 4.9%. Positive biopsies were
observed in 15 of 46 patients (32.6%) who underwent prostate
biopsy after SCAP A case-matched control study
compared SRP and SCAP. The 5-yr BCR-FS rate was 61%
following SRP, significantly better than the 21% rate observed
after SCAP. The 5-yr OS rate was also significantly higher in the
SRP group (95% vs 85%) . With the use of third-generation
technology, SCAP complication rates have decreased; a recent
study reported an incontinence rate of 12%, retention in 7% of
patients, rectourethral fistulae in 1.8%, and ED in 83%
For carefully selected patients with primary localised
PCa and histologically proven local recurrence, high-dose
rate (HDR) or low-dose rate (LDR) brachytherapy is another
salvage option with an acceptable toxicity profile .
Fifty-two patients were treated at the Scripps Clinic with
HDR brachytherapy over a period of 9 yr With a
median follow-up of 60 mo, the 5-yr biochemical control
rate was 51%, and only 2% grade 3 genitourinary toxicities
were reported. Comparable results came from a 42-patient
phase 2 trial at Memorial Sloan Kettering Cancer Center
Of note, the median pretreatment dose was 81 Gy given
with intensity-modulated RT, and the prescription HDR dose
of 32 Gy was delivered in four fractions over 30 h. The BCR-
FS rate after 5 yr was 69% (median follow-up of 36 mo).
Grade 2 late side effects were seen in 15%, and one patient
developed grade 3 incontinence. These data contrast with
earlier studies reporting higher rates of side effects
Using LDR brachytherapy with Pd 103, long-term
outcome was reported in 37 patients with a median
follow-up of 86 mo . The biochemical control rate after
10 yr was 54%; however, the crude rate of grade 2 toxicity
was 46%, and grade 3 toxicity was 11%. These side effects
were comparable with a series of 31 patients treated with
salvage I 125 brachytherapy in the Netherlands. Freedom
from BCR after salvage HDR and LDR brachytherapy is
promising, and the rate of severe side effects at experienced
centres seems to be acceptable, although numbers are
small.
Salvage HIFU has also emerged as an alternative thermal
ablation option for radiation-recurrent PCa. Most of the data
have been generated by one high-volume centre . With
a median follow-up of 48 mo, 56% of men required ADT.
Complication rates are comparable to other salvage
treatment options, with a 0.4% rate of rectourethral fistula
and a 19.5% incidence rate of grade 2/3 incontinence
).
2.5. Management of nodal relapse only
BCR rates were found to be associated with PSA at surgery
and location and number of positive nodes . The
majority of patients treated surgically showed BCR as a
consequence of micrometastatic deposits not detected with
PET/CT scan. 11C-choline PET/CT has shown good sensitivi-
ty and specificity for the early detection of nodal metastases
after RP . Salvage lymph node dissection (LND) can
achieve a complete biochemical response in a proportion of
patients. However, most patients progress to BCR within 2
yr after surgery . The ideal candidates for salvage
LND have not been identified yet, and this approach should
be reserved for highly selected patients only
).
3. Systemic disease control )
In patients with nonmetastatic localised PCa not suitable for
curative treatment, ADT should be used only in patients
requiring symptom palliation. In men with asymptomatic
locally advanced T3–4 disease or BCR after attempt at cure,
ADT may benefit patients with PSA >50 ng/ml and PSA DT
< 12 mo , but routine use should be avoided .
In symptomatic metastatic patients, immediate treat-
ment is mandatory; however, controversy still exists
E U R O P E A N U R O L O G Y 7 1 ( 2 0 1 7 ) 6 3 0 – 6 4 2 632