Initial systemic therapy for castration sensitive prostate cancer
- Richard J Lee, MD, PhD
Richard J Lee, MD, PhD
- Assistant Professor of Medicine
- Harvard Medical School
- Massachusetts General Hospital
- Matthew R Smith, MD, PhD
Matthew R Smith, MD, PhD
- Professor of Medicine
- Harvard Medical School
- Massachusetts General Hospital Cancer Center
- Section Editors
- Nicholas Vogelzang, MD
Nicholas Vogelzang, MD
- Section Editor — Prostate Cancer
- Professor of Medicine
- University of Nevada School of Medicine
- US Oncology Research
- W Robert Lee, MD, MS, MEd
W Robert Lee, MD, MS, MEd
- Section Editor — Prostate Cancer
- Professor of Radiation Oncology
- Duke University Medical Center
- Jerome P Richie, MD, FACS
Jerome P Richie, MD, FACS
- Section Editor — Cancer of the Urethra, Penis, and Ureter; Urologic Surgery; Prostate Cancer
- Elliott Carr Cutler Professor of Surgery
- Harvard Medical School
The critical role of androgens in stimulating prostate cancer growth was established in 1941 by Charles Huggins [1,2]. These findings led to the development of androgen deprivation therapy (ADT) as the treatment for patients with advanced prostate cancer.
Although ADT is palliative, it can normalize serum levels of prostate-specific antigen (PSA) in over 90 percent of patients and can produce objective tumor responses in 80 to 90 percent. This antitumor activity can improve quality of life by reducing bone pain as well as the rates of complications (eg, pathologic fracture, spinal cord compression, ureteral obstruction).
The duration of response to ADT for patients with metastatic disease is highly variable, and most prostate cancer patients eventually experience disease progression despite treatment. Patients who have progressed while on ADT are said to have castration resistant disease, although such tumors may remain responsive to additional therapies directed against androgenic stimulation of the prostate cancer.
Docetaxel was subsequently shown to prolong survival in men with castration resistant prostate cancer. Randomized controlled trials have demonstrated that chemohormonal therapy combining docetaxel with ADT offers a clinically meaningful survival advantage for patients with castration sensitive metastatic disease. (See "Chemotherapy in castration-resistant prostate cancer", section on 'Chemotherapy-naive patients' and 'Chemohormonal therapy' below.)
The initial therapy for men with castration sensitive metastatic prostate cancer will be reviewed here. An overview of the treatment of disseminated prostate cancer is presented separately, as are special considerations for patients whose only manifestation of disseminated disease is a rising serum PSA. (See "Overview of the treatment of disseminated prostate cancer" and "Rising serum PSA after treatment for localized prostate cancer: Systemic therapy".)
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- ANDROGEN DEPRIVATION THERAPY
- Surgical orchiectomy
- Efficacy of initial ADT
- Medical orchiectomy
- - Gonadotropin-releasing hormone agonists
- Mechanism of action
- Serum testosterone level
- GnRH agonists versus orchiectomy
- - GnRH antagonists
- - Combined androgen blockade with antiandrogens
- Initiation of ADT
- Long-term combined androgen blockade
- - Intermittent androgen deprivation
- Metastatic disease
- Rising PSA
- - Timing of treatment initiation
- Symptomatic metastases
- Asymptomatic metastases
- Rising serum PSA
- Other hormonal approaches
- - Antiandrogen monotherapy
- - Enzalutamide
- CHEMOHORMONAL THERAPY
- - STAMPEDE trial
- - CHAARTED trial
- - GETUG-AFU 15 trial
- PREVENTION OF OSTEOPOROSIS
- SIDE EFFECTS OF ANDROGEN DEPRIVATION THERAPY
- SURVEILLANCE DURING TREATMENT
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS