EURURO Vol. 72 No. 5

700 860

the HD study. The RAVES trial is a phase 3 multicenter trial
performed in Australia and New Zealand that randomizes
patients to aRT versus sRT administered within 4 mo following
the first PSA 0.2 ng/ml. Overall, 470 patients will be included
and accrual is expected to be completed by the end of the year
Finally, the GETUG-17 trial is a French study that aims at
comparing aRT + luteinizing hormone-releasing hormone ago-
nists versus sRT + luteinizing hormone-releasing hormone
agonists in men with pT3R1 pN0 or pNx disease at RP.
3.8. How can we optimize postoperative RT? Optimal dose,
volume, and technique
The association between RT dose and oncologic outcomes
observed in the primary setting led to the hypothesis that
higher doses might be beneficial even in men undergoing
postoperative RT . Although the median dose delivered
to patients undergoing immediate RT included in random-
ized trials was 60–64 Gy retrospective studies
proposed a role for dose escalation. Cozzarini et al
observed that patients undergoing aRT treated with 70 Gy
had significantly improved BCR-free and cancer-specific
survival rates compared with those receiving <70 Gy at a
median follow-up of 108 mo. When considering sRT, clinical
guidelines suggest that a minimum dose of 64–65 Gy should
be delivered. Nonetheless, the beneficial impact of dose
escalation on BCR-free and complete remission-free survival
has also been observed in this context .
Stish et al reported that the delivery of 68 Gy or greater
significantly reduced the risk of BCR in a large contemporary
cohort of men undergoing sRT. Two systematic reviews
addressed this issue, reporting a 2–2.5% improvement in
recurrence-free survival for each additional Gy delivered
Of note, one prospective trial currently randomizes
patients undergoing sRT to 64 Gy or 70 Gy (NCT01272050)
and its oncologic results are needed to comprehensively
assess the role of dose escalation in patients undergoing sRT.
The use of pelvic radiation in addition to the prostate and
seminal vesicle bed RT might be associated with improved
oncologic outcomes This approach would allow
potentially maximize disease control by sterilizing sites of
micrometastases in the pelvic lymph nodes. Spiotto et al
evaluated 114 patients undergoing aRT or sRT
considered at high risk of lymph node involvement
according to pathologic characteristics. The authors
reported an advantage in BCR-free survival in men treated
with whole-pelvis RT (WPRT) compared with prostate bed
irradiation only at a median follow-up >5 yr. Similarly,
Moghanaki et al evaluated patients receiving sRT
without ADT and showed that WPRT was associated with
improved BCR-free survival only when administered at pre-
RT PSA levels >0.4 ng/ml. Song et al confirmed these
findings and reported that the greatest advantage associat-
ed with WPRT was in men with more aggressive disease
characteristics and higher risk of lymph node invasion.
Finally, a comprehensive tumor control probability model
recently suggested that recurrence is often related to
relapse outside the irradiated volume and supported the
role for lymph-node irradiation in patients with Gleason
score <7 and PSA levels 1 ng/ml or in those with Gleason
score 7 and PSA >0.3 ng/ml . However, smaller studies
have reported conflicting results Further informa-
tion about the role of WPRT will be provided by the RTOG
05-34 trial (NCT00567580), comparing progression-free
survival between patients randomized to prostatic bed RT
alone short-term ADT or WPRT short-term ADT.
Finally, the oncologic benefits associated with novel
techniques such as intensity-modulated RT (IMRT) are still
debated, where recent studies failed to show an advantage
of these approaches over three-dimensional conformal RT
in terms of BCR-free and metastases-free survival
However, IMRT allows a sculpting of high doses
around the tumor bed and the pelvic area with deep dose
gradients. The potential advantages of this approach might
result in a reduced incidence of toxicities associated with
postoperative RT
3.9. Concomitant administration of ADT
Although several retrospective studies reported that the
addition of ADT to postoperative RT might be beneficial in
terms of BCR-free survival conflicting
data exist on the role of hormonal treatment on stronger
endpoints such as metastases-free and overall survival
The rationale for the use of hormonal
manipulation during aRT or sRT might be an effect on
subclinical metastases. In this context, the greatest oncologic
benefit associated with concomitant ADT was observed in
men with more aggressive disease characteristics .
Jackson et al recently evaluated a cohort of more than
600 patients treated with aRT or sRT and reported that
concomitant ADT significantly improved BCR-free survival.
Moreover, the use of hormonal manipulation for 1 yr or more
had an impact on the subsequent risk of BCR and clinical
recurrence in men with high-risk features (ie, Gleason score
8–10, seminal vesicle involvement, and/or pre-RT
PSA > 1 ng/ml). The RADICALS HT trial is currently random-
izing patients to no ADT versus 6-mo ADT versus 24-mo ADT
with a gonadotropin-releasing hormone (GnRH) agonist and
will help to clarify the role of ADT during postoperative RT.
When considering patients treated exclusively in a
salvage setting, the results of two randomized controlled
trials addressing this issue were recently published
The GETUG-AFU-16 trial (NCT00423475) random-
ized 743 patients who experienced BCR after RP to RT alone
versus RT plus 6-mo goserelin. All patients included in this
study had complete biochemical response after surgery. At
5-yr follow-up, patients treated with sRT plus ADT had
higher BCR-free and CR-free survival rates as compared to
their counterparts receiving sRT alone. No differences were
observed in late adverse effects between the two groups.
However, a longer follow-up is needed to evaluate the
impact of short-term ADT on survival. The RTOG 9601 trial
randomized 761 patients with detectable PSA or BCR after
surgery to sRT alone versus sRT plus 24-mo bicalutamide
At a median follow-up of 12.6 yr, patients treated with
sRT plus ADT had significantly higher clinical recurrence-
free and cancer-specific and overall survival rates. Late
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