E U R O P E A N U R O L O G Y 6 0 ( 2 0 1 1 ) 1 3 0 3 – 1 3 0 81306
Lawrence C. Jenkinsa, Michael A. Gorina, Gaetano Ciancioa,b,*
aDepartment of Urology, University of Miami Miller School of Medicine,
Miami, FL, USAbDepartment of Surgery, Division of Transplantation,
University of Miami Miller School of Medicine, Miami, FL, USA
*Corresponding author. University of Miami Miller School of
Medicine, Post Office Box 012440, Miami, FL 33101, USA.
E-mail address: [email protected] (G. Ciancio)
DOI: 10.1016/j.eururo.2011.08.068
Re: Radiotherapy and Short-Term Androgen Deprivationfor Localized Prostate Cancer
Jones CU, Hunt D, McGowan DG, et al
N Engl J Med 2011;365:107–18
Expert’s summary:
Radiation Therapy Oncology Group (RTOG) 94-08 was a large
randomized trial comparing external beam radiotherapy
(EBRT) alone with EBRT plus 4 mo of neoadjuvant hormone
therapy (NAHT) in men with clinically localized prostate
cancer. Starting in 1994, the trial accrued 1979 men with
a prostate-specific antigen level of <20 ng/ml. They received
EBRT at doses of 46.8 Gy to the pelvis and 66.6 Gy to the
prostate using 1.8-Gy fractions. Those randomized to NAHT
received four monthly luteinizing hormone-releasing hor-
mone agonist injections and flutamide 250 mg three times
per day, with EBRT starting after 2 mo. The primary end
point was overall survival. Ten-year overall survival was
significantly improved by the use of NAHT (62% vs 57%;
hazard ratio [HR]: 0.85; 95% confidence interval [CI], 0.74–
0.99; p = 0.03). Ten-year prostate cancer–specific mortality
was reduced by the use of NADT (4% vs 8%; HR: 0.53;
p = 0.001). No significant differences were seen in terms of
late toxicity.
Expert’s comments:
This trial will be dismissed by some oncologists on the
grounds that the radiotherapy technique used is now outdat-
ed; however, that would be a mistake. There are not many
large, mature, randomized trials for the treatment of localized
prostate cancer. There are even fewer that show a significant
overall survival advantage in the absence of any late toxicity.
The magnitude of benefit for NAHT is remarkable, with the
risk of death from prostate cancer reduced by half. In compar-
ison with the recent data on radical prostatectomy (vs watch-
ful waiting) from the Prostate Cancer Intervention Versus
Observation Trial (PIVOT) trial [1], NAHT appears both more
effective and far less toxic.
It would also be a mistake to conclude that RTOG 94-08
shows that NAHT is not needed for low-risk disease. The
subgroup analysis by risk group was unplanned, and there
was no significant interaction between risk group and
treatment effect in terms of overall survival. It is true that
many men with low-risk disease have harmless cancers that
do not need any treatment. As we become better at
identifying which so-called low-risk cancers need treat-
ment, the absolute benefit from NAHT will increase.
The benefit of NAHT in men receiving modern, high-dose
radiotherapy remains uncertain; however, whereas NAHT
halves the risk of prostate cancer death, the effect of
radiotherapy dose escalation on mortality remains unproven.
Furthermore, whereas the morbidity of NAHT is temporary,
radiotherapy dose escalation has permanent sequelae.
Arguably, the more important issue is not whether NAHT
improves the outcome of modern radiotherapy but rather
whether radiotherapy dose escalation is required in men
receiving NAHT.
Conflicts of interest: The author has nothing to disclose.
Reference
[1] Wilt TJ. The VA/NCI/AHRQ CSP#407: Prostate Cancer Intervention
Versus Observation Trial (PIVOT): main results from a randomized
trial comparing radical prostatectomy to watchful waiting in men
with clinically localized prostate cancer. Plenary presentation at:
American Urological Association Annual Meeting; May 14-19, 2011;
Washington, DC, USA.
Chris Parker
Royal Marsden Hospital, Sutton, UK
E-mail address: [email protected]
DOI: 10.1016/j.eururo.2011.08.069
Re: Randomised Prostate Cancer Screening Trial: 20 YearFollow-up
Sandblom G, Varenhorst E, Rosell J, Lofman O, Carlsson P
BMJ 2011;342:d1539
Experts’ summary:
Prostate cancer (PCa) screening continues to generate contro-
versy. Both the European Randomized Study of Prostate Cancer
Screening and the Goteborg randomized screening trial
reported significant reductions in PCa-specific mortality
with prostate-specific antigen (PSA)–based screening [1,2],
whereas the US Prostate, Lung, Colorectal and Ovary cancer-
screening trial reported no mortality difference between
men randomized to screening compared with controls [3].
Adding to this debate is this recent study by Sandblom
et al. In 1987, 9026 men aged 50–69 yr in Norrkoping,
Sweden, were identified through the National Population