The licensed indication for bicalutamide 150 mg has recently changed in the UK and several other countries. In the UK, bicalutamide 150 mg is indicated as an alternative to castration for patients with locally advanced prostate cancer, either alone or as an adjuvant therapy; it is no longer indicated in patients with localized disease who would normally be managed by observation. Whilst it would be unusual to commence hormone treatment in patients with clinically localized prostate cancer who would otherwise undergo watchful waiting, there nevertheless remains a degree of uncertainty within the clinical community about which patients should and should not be considered for bicalutamide 150 mg. This article reviews the conclusions of the most recent analysis of the bicalutamide Early Prostate Cancer (EPC) programme that have led to the changes in the license for prescribing bicalutamide 150 mg, and considers their clinical implications.
The ongoing EPC programme is the world's largest prostate cancer treatment study, involving >8000 patients . Initiated in 1996, it consists of three complementary randomized, double-blind, placebo-controlled trials examining whether adding bicalutamide 150 mg/day to standard care (be it radical prostatectomy, radiotherapy or watchful waiting) can reduce the risk of prostate cancer progression and improve overall survival in patients with localized or locally advanced disease.
The latest analysis of the EPC programme data, in 2003 at a median of 5.4 years of follow-up , confirmed previous findings  that bicalutamide 150 mg significantly delays disease progression (hazard ratio, HR, 0.73; P < 0.001)  and prolongs the time to PSA failure (HR 0.49; P < 0.001)  compared with standard care alone. The greatest benefit was in patients at highest risk of progression. Given the relatively early stage of the study, it is hardly surprising that in the overall results there was no difference in survival between patients receiving placebo or bicalutamide 150 mg (HR 1.03; P = 0.58; 15% mortality) .
Further exploratory analyses, beyond the remit of the original protocol, revealed no difference in survival across all subgroups, except in those patients managed by observation. Within the watchful-waiting subgroup, with bicalutamide 150 mg there was a small trend toward reduced survival in patients with localized disease (HR 1.23; 95% CI 1.00–1.50) but a small trend toward prolonged survival in patients with locally advanced disease (HR 0.81; 95% CI 0.63–1.04) compared with observation alone . The reduction in deaths in patients with locally advanced disease receiving bicalutamide was driven by a reduction in prostate cancer mortality. The increased deaths in patients with localized disease receiving bicalutamide was caused by a relative increase in deaths related to causes other than prostate cancer, which appear unrelated to any one specific cause .
So who should be considered for bicalutamide 150 mg therapy? The latest results from the EPC programme have shown that the greatest progression-free survival benefits for this treatment are in patients with locally advanced disease. As such patients are at significant risk of disease progression, any additional therapies that can reduce this risk, with minimal effects on lifestyle, are important.
The standard care for patients with locally advanced disease is often external-beam radiotherapy and, in this setting, the EPC programme data show that adding bicalutamide 150 mg as adjuvant therapy significantly reduces the risk of disease progression (HR 0.58; P = 0.0035) . Furthermore, many patients with clinically localized disease who have had a radical prostatectomy are re-staged by the pathologist to pT3, or locally advanced disease, and here again adjuvant bicalutamide 150 mg significantly reduced the risk of disease progression (HR 0.71; P = 0.0034) . Patients with locally advanced disease are not always suitable for, or opt not to receive, local therapy; under these circumstances, bicalutamide 150 mg again showed a significant risk reduction in terms of disease progression compared with observation alone (HR 0.53, P < 0.001) . Moreover, as bicalutamide 150 mg has important quality-of-life advantages over castration, in terms of maintaining libido, allowing better physical activity and preserving normal bone mineral density [8,9], it offers an attractive alternative to androgen deprivation by surgical or medical castration.
In summary, the EPC programme continues to show, at a median of 5.4 years of follow-up, that bicalutamide 150 mg provides an important clinical benefit for patients with prostate cancer by reducing the risk of disease progression for those with locally advanced disease. It will be important to see whether these clinical benefits are maintained over time and ultimately translate into a survival advantage.