Continuing Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer

Rationale for Continuing ADT

The National Comprehensive Cancer Network recommends continuing androgen deprivation therapy (ADT) with an LHRH agonist or antagonist indefinitely in patients with metastatic castration-resistant prostate cancer (mCRPC) to maintain castrate serum testosterone levels (<50 ng/dL) 1, 2, 3
Castration-resistant disease does not mean androgen-independent disease, as prostate cancer cells remain dependent on residual androgen signaling from non-gonadal sources, including intratumoral androgen synthesis and adrenal production 4
All novel therapies for mCRPC are studied and approved with concurrent ADT as the backbone, demonstrating survival benefits while maintaining castrate testosterone levels 1, 2, 5

The National Comprehensive Cancer Network recommends verifying serum testosterone is <50 ng/dL (<1.7 nmol/L) through laboratory testing before diagnosing CRPC, and optimizing ADT delivery or switching LHRH agents if testosterone is not adequately suppressed 1, 2
Secondary hormone therapies, such as abiraterone + prednisone, enzalutamide, or other androgen receptor pathway inhibitors, should be added on top of continued ADT, not as replacements 1, 2, 6
Chemotherapy, such as docetaxel or cabazitaxel, should be added on top of continued ADT, not as replacements 1, 5, 6
Immunotherapy, such as sipuleucel-T, should be added on top of continued ADT, not as replacements 5
Radiopharmaceuticals, such as radium-223, should be added on top of continued ADT, not as replacements 5
Targeted therapies, such as PARP inhibitors for HRR mutations, or 177Lu-PSMA-617 for PSMA-positive disease, should be added on top of continued ADT, not as replacements 1, 6

The 2023 NCCN Guidelines explicitly state that ADT should be continued in patients with mCRPC while additional therapies are sequentially applied, with the highest level of evidence support 1, 2, 3
The 2014 ASCO/Cancer Care Ontario guideline recommends continuing androgen deprivation indefinitely regardless of additional therapies, with moderate benefit and moderate recommendation strength 5
Multiple guidelines from 2013-2023 consistently emphasize the principle of continuing ADT without exception, with high-level evidence support 1, 4, 5, 7, 8

Testosterone levels should be monitored periodically to ensure maintenance of castrate levels throughout treatment, as recommended by the National Comprehensive Cancer Network 1
ADT should be continued even when PSA becomes undetectable, as radiographic progression can still occur, as recommended by the National Comprehensive Cancer Network 1
ADT should be maintained through all lines of therapy until end-of-life care, as recommended by the American Society of Clinical Oncology 5