Prostate Cancer Diagnosis and First-Line Treatment for Primary Care Providers
Risk Stratification is the Critical First Step
Treatment decisions for prostate cancer must be stratified by disease stage and risk category—localized disease is managed through active surveillance, surgery, or radiation therapy, while metastatic disease requires androgen deprivation therapy as the foundation of treatment. 1
Before selecting any treatment, you must classify patients into risk categories based on three key parameters: PSA level, Gleason score (or ISUP grade), and clinical stage 1. This risk stratification determines both prognosis and guides all subsequent therapeutic decisions 1.
Risk Categories:
- Low risk: T1-2a, Gleason ≤6 (ISUP 1), PSA <10 ng/mL 2
- Intermediate risk: T2b-2c, Gleason 7 (ISUP 2-3), or PSA 10-20 ng/mL 3
- High risk: T3a or Gleason 8-10 (ISUP 4-5) or PSA >20 ng/mL 2
Staging Workup Requirements
For intermediate and high-risk disease, you must obtain bone scintigraphy and cross-sectional imaging (CT or MRI of abdomen/pelvis) to evaluate for metastases 2, 1. High-risk patients also require chest CT 2. Do not deny patients radical local treatment solely because novel imaging techniques (like PSMA-PET) identify metastatic lesions when conventional imaging shows localized disease 2.
Treatment Algorithm by Risk Category and Life Expectancy
Low-Risk Disease
For patients with life expectancy <10 years: Watchful waiting (observation without curative intent) is the recommended approach, with delayed hormone therapy only if symptomatic progression occurs 1.
For patients with life expectancy ≥10 years: Active surveillance is the preferred option 1. This involves:
- PSA measurement every 6 months 1
- Digital rectal examination every 12 months 1
- Repeat prostate biopsy every 12 months 1
Active surveillance avoids treatment-related morbidity while maintaining the option for curative intervention if disease progresses 1. This approach is appropriate for approximately one-third of patients with localized prostate cancer 4.
Alternative curative options for low-risk disease include 1:
- Radical prostatectomy
- External beam radiation therapy (minimum 70 Gy in 2.0 Gy fractions) 3
- Low-dose-rate brachytherapy 3
All three modalities have similar outcomes for low-risk disease, with 10-year survival rates of 90-94% 2. The choice depends heavily on patient preferences regarding side effects 5.
Intermediate-Risk Disease (Including Gleason 7)
For patients with life expectancy >10 years, the standard options are 1, 3:
Radical prostatectomy: Complete removal of the prostate with accurate pathological staging 3. Be aware that this carries up to 80% risk of erectile dysfunction and up to 49% risk of urinary incontinence 3.
External beam radiation therapy: Minimum target dose of 70 Gy 3. Add neoadjuvant and concurrent androgen deprivation therapy for 4-6 months—this improves local control, reduces disease progression, and improves overall survival 2, 3.
Brachytherapy: Can be used as monotherapy for Gleason 3+4=7 with PSA <10 ng/mL, or as a boost with external beam radiation 3. However, use cautiously in patients with significant lower urinary tract symptoms as it can exacerbate urinary obstruction 3.
Critical pitfall: Do NOT use primary androgen deprivation therapy alone as standard initial treatment for localized disease 2, 3. This is a common error.
High-Risk and Locally Advanced Disease
The standard approach is external beam radiation therapy plus hormone treatment 2, 1. Specifically:
- Neoadjuvant and concurrent ADT for 4-6 months 2
- Adjuvant ADT for 2-3 years for patients at high risk of prostate cancer mortality 2
Alternative: Radical prostatectomy plus pelvic lymphadenectomy 2, 1.
The addition of androgen suppression to radiation significantly improves local control, reduces disease progression, and improves overall survival in intermediate or high-risk disease 2.
Metastatic Disease: First-Line Treatment
Continuous androgen deprivation therapy is the recommended first-line treatment for metastatic hormone-naïve prostate cancer 2, 1. This is achieved through:
- Medical castration: LHRH agonists (e.g., goserelin) 2, 6
- Surgical castration: Bilateral orchiectomy 2
When initiating LHRH analogs, accompany with an antiandrogen for 4 weeks to prevent tumor flare 2. There is no proven benefit for continuing total androgen blockade beyond this initial 4-week period 2.
Enhanced First-Line Regimens for Metastatic Disease
For patients fit enough for chemotherapy, adding docetaxel to ADT at initial diagnosis provides significant survival benefit 2, 1, 4. This represents a paradigm shift from sequential therapy 1.
For patients who cannot tolerate chemotherapy, adding androgen receptor pathway inhibitors to ADT improves survival 2, 1, 4:
- ADT + abiraterone: Improved median overall survival from 36.5 months to 53.3 months (HR 0.66) 4
- ADT + enzalutamide 2, 1
- ADT + apalutamide 2, 1
- ADT + darolutamide 2
For low-volume metastatic disease, consider adding radiation therapy to the primary tumor 2.
Critical Caveats and Monitoring
Prevent Gynecomastia
To prevent painful gynecomastia when initiating antiandrogen therapy, give breast irradiation (8-15 Gy in 1-3 fractions) 1-2 weeks before starting treatment 2.
Monitor for ADT Complications
Patients on long-term ADT require monitoring for 2, 1:
- Osteoporosis (using bone densitometry) 2
- Metabolic syndrome 2
- Hyperglycemia and diabetes 6
- Cardiovascular disease 6
Recommend regular exercise to all men on ADT—this reduces fatigue and improves quality of life 2, 1.
Post-Treatment Surveillance
After radical prostatectomy, PSA should be undetectable (<0.2 ng/mL) within 2 months 1. Follow-up includes 1:
- PSA measurement every 3 months during year 1
- Then every 6 months for 7 years
- Digital rectal examination is optional if PSA remains undetectable
For biochemical recurrence (rising PSA), salvage radiation therapy to the prostate bed should be initiated early (PSA <0.5 ng/mL) for best outcomes 2, 1.
Avoid Common Errors
Do not use cryotherapy, HIFU, or focal therapy as standard initial treatments for localized prostate cancer 1. Do not give adjuvant radiotherapy immediately following radical prostatectomy—it has not been shown to improve survival 3.