Prostate Cancer Management
Treatment for prostate cancer must be selected based on risk stratification using PSA level, Gleason score, and clinical stage, with active surveillance preferred for low-risk disease, radical prostatectomy or radiotherapy for intermediate-risk disease, and radiotherapy plus androgen deprivation therapy (ADT) for high-risk localized disease, while metastatic disease requires ADT combined with docetaxel or androgen receptor pathway inhibitors. 1
Risk Stratification Framework
Risk classification determines the entire treatment approach and must be performed before selecting therapy 1:
- Low-risk disease: PSA <10 ng/mL AND Gleason score ≤6 AND clinical stage T1-T2a 1
- Intermediate-risk disease: PSA 10-20 ng/mL OR Gleason score 7 OR clinical stage T2b 1
- High-risk disease: PSA >20 ng/mL OR Gleason score 8-10 OR clinical stage T2c 1
Life expectancy is critical—curative treatment should not be pursued if life expectancy is <10 years, as the benefit is minimal 1.
Treatment by Risk Category
Low-Risk Localized Disease
Active surveillance is the preferred approach for low-risk prostate cancer 1. This involves serial PSA measurements, prostate biopsies, or MRI monitoring with treatment initiation only if Gleason score or tumor stage increases 2. This strategy avoids overtreatment while maintaining excellent outcomes, as low-risk localized disease has a nearly 100% 5-year survival rate 2.
Alternative curative options for low-risk disease include 1:
- Radical prostatectomy
- External beam radiotherapy
- Brachytherapy (particularly appropriate for low-risk tumors at any age) 1, 3
Intermediate-Risk Localized Disease
Radical prostatectomy and external beam radiotherapy are equally effective treatment options for intermediate-risk disease 1. The choice between these modalities should be based on patient preferences regarding side effects, as both can cause urinary symptoms and sexual dysfunction 4.
- Brachytherapy may be considered for select intermediate-risk patients 1
- External beam radiotherapy may include neoadjuvant and concurrent ADT for 4-6 months 1
High-Risk Localized Disease
External beam radiotherapy combined with ADT is the standard approach for high-risk localized prostate cancer 1. Radical prostatectomy remains an option but radiotherapy with ADT provides superior outcomes in this population 1.
Locally Advanced Disease (Stage T2b-T4/B2-C)
For locally confined Stage T2b-T4 prostate cancer, combination therapy with ZOLADEX (goserelin) plus flutamide should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy 5. This approach is FDA-approved and provides optimal disease control 5.
Post-Treatment Management
After Radical Prostatectomy
Salvage radiotherapy to the prostate bed should be initiated early (PSA <0.5 ng/mL) for biochemical recurrence 1. Delayed salvage radiotherapy significantly reduces effectiveness—this is a critical pitfall to avoid 1.
After Radiotherapy
Early ADT is not routinely recommended after radiotherapy unless patients have 1:
- Symptomatic local disease
- Proven metastases
- PSA doubling time <3 months
Metastatic Disease Management
Metastatic Hormone-Naïve Prostate Cancer
Continuous ADT plus docetaxel chemotherapy is first-line treatment for patients fit enough to receive it 1, 6. This combination significantly improves survival compared to ADT alone 2.
For patients receiving ADT 6:
- When starting an LHRH agonist (such as goserelin), an antiandrogen should be given for 3-4 weeks to prevent testosterone flare
- Regular exercise should be recommended to reduce fatigue and improve quality of life
- Intermittent ADT is not recommended outside clinical trials unless significant intolerance occurs
Adding androgen receptor pathway inhibitors (abiraterone or darolutamide) to ADT improves median overall survival from 36.5 months to 53.3 months (hazard ratio 0.66) 2.
Castration-Resistant Prostate Cancer (CRPC)
Treatment options for metastatic CRPC include 1, 6:
- Abiraterone or enzalutamide for asymptomatic/mildly symptomatic chemotherapy-naïve patients
- Docetaxel chemotherapy for symptomatic patients or those progressing on hormonal therapy
- Radium-223 for bone-predominant, symptomatic disease without visceral metastases
- Denosumab or zoledronic acid for patients at high risk for skeletal-related events
Supportive Care for Bone Metastases
- A single fraction of external beam radiotherapy is recommended for palliation of painful bone metastases 6
- MRI of the spine should be performed to detect subclinical cord compression in men with vertebral metastases 6
Monitoring During Treatment
Patients on long-term ADT require monitoring for 6:
- Osteoporosis using bone densitometry
- Metabolic syndrome
- PSA levels and clinical assessment
- Initial imaging with bone scan and CT/MRI of abdomen and pelvis (systematic surveillance imaging not mandatory without PSA rise or symptoms)
Critical Pitfalls to Avoid
- Overtreatment of low-risk disease: Proper counseling about active surveillance as a safe option is essential 1
- Delayed salvage radiotherapy: Most effective when PSA is <0.5 ng/mL after prostatectomy 1
- Inadequate biopsy sampling: Minimum of 10-12 cores should be obtained 1
- Ignoring life expectancy: Curative treatment offers minimal benefit when life expectancy is <10 years 1
- PSA unreliability in neuroendocrine variants: PSA is not a reliable indicator in undifferentiated metastatic prostate cancer with neuroendocrine features, and these patients should receive chemotherapy plus ADT 6