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: gciancio@med.miami.edu (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: chris.parker@icr.ac.uk

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