Is Bicalutamide (Casodex) alone without Leuprolide (Lupron) acetate adequate treatment for hormone-sensitive prostate cancer?

Bicalutamide Alone is NOT Adequate Treatment for Prostate Cancer

Bicalutamide monotherapy without leuprolide is inadequate for treating prostate cancer and is explicitly not approved by the FDA for use alone—the FDA label clearly states that bicalutamide 50 mg is indicated only "in combination therapy with an LHRH analog" and that "bicalutamide 150 mg daily is not approved for use alone or with other treatments." 1

Why Combination Therapy is Required

FDA-Approved Indication

• Bicalutamide 50 mg is FDA-approved exclusively for combination with an LHRH analog (such as leuprolide) for Stage D2 metastatic prostate cancer 1
• The FDA explicitly states that bicalutamide 150 mg daily is NOT approved for monotherapy 1
• Treatment with bicalutamide should be started at the same time as the LHRH analog 1

Guideline Recommendations Strongly Favor Combination Therapy

For locally advanced nonmetastatic disease:

• The American Society of Clinical Oncology (ASCO) recommends ADT (castration with leuprolide or goserelin) plus abiraterone and prednisolone as the preferred first-line treatment, showing a 79% relative improvement in failure-free survival 2
• In resource-constrained settings where abiraterone is unavailable, combined androgen blockade using ADT plus bicalutamide may be offered rather than castration monotherapy 2

The evidence hierarchy clearly shows:

• Combined androgen blockade (LHRH agonist + bicalutamide) demonstrates superior outcomes compared to castration alone, with median time to progression of 11.6 years versus 7.1 years (HR 0.78, P < .001) 2
• Meta-analyses show combined androgen blockade with nonsteroidal antiandrogens improves overall survival (HR 0.88,95% CI 0.82-0.95, P = 0.0009) and progression-free survival (HR 0.85,95% CI 0.73-0.98, P = 0.007) compared to castration monotherapy 2

Why Bicalutamide Monotherapy Fails

Insufficient Testosterone Suppression

• When used alone, bicalutamide 50 mg does not lower testosterone levels—it only blocks androgen receptors 3
• The reduction in testosterone from castration (surgical or medical with leuprolide) decreases competition between bicalutamide and testosterone for androgen receptors, allowing effective androgen blockade 3
• Without castration, higher doses of bicalutamide (150 mg) would be needed, but even this is not FDA-approved 1, 3

Evidence Against Monotherapy

• Early trials showed bicalutamide 50 mg monotherapy is less effective than castration 4
• Even at 150 mg daily, bicalutamide monotherapy showed a small but significant survival shortfall (median difference 42 days) compared to castration in metastatic disease 5
• Bicalutamide 150 mg monotherapy showed equivalent survival to castration only in the subgroup with locally advanced nonmetastatic disease, not in metastatic disease 5, 3

Clinical Algorithm for Treatment Selection

For metastatic (Stage D2) prostate cancer:

1. First-line: ADT (leuprolide or goserelin) + abiraterone + prednisolone 2
2. Alternative if abiraterone unavailable: ADT + bicalutamide 50 mg daily 2, 1
3. Never use bicalutamide 50 mg alone 1

For locally advanced nonmetastatic disease:

1. Preferred: ADT + abiraterone + prednisolone (especially with radiation therapy) 2
2. Alternative: Combined androgen blockade (ADT + bicalutamide 50 mg) 2
3. Bicalutamide monotherapy is not standard of care 2

For biochemically recurrent disease after radiation:

• ADT with leuprolide or goserelin is recommended 6
• ADT plus abiraterone and prednisolone is preferred based on STAMPEDE trial 6
• Combined androgen blockade (ADT + bicalutamide) is an acceptable alternative 6

Critical Pitfalls to Avoid

• Do not prescribe bicalutamide 50 mg as monotherapy—this violates FDA approval and provides inadequate androgen suppression 1
• Do not use bicalutamide 150 mg as monotherapy—this is explicitly not FDA-approved despite some international approvals 1
• Do not delay combination therapy—bicalutamide should be started simultaneously with the LHRH analog 1
• Monitor liver function—hepatotoxicity can occur within the first 3-4 months, requiring baseline and regular monitoring 1

Tolerability Considerations

While bicalutamide monotherapy theoretically offers better preservation of sexual function and quality of life compared to castration 5, 4, 7, this potential benefit cannot justify using an inadequate treatment that compromises survival outcomes. The appropriate approach is to use the FDA-approved combination of bicalutamide 50 mg with leuprolide, which provides both efficacy and acceptable tolerability 2, 1.