What are the treatment options for early prostate cancer, including observation and therapies like surgery, radiation, hormone therapy with medications such as leuprolide (leuprolide) or goserelin (goserelin), and second-line interventions?

Treatment of Early Prostate Cancer: Observation vs Active Therapies

For early prostate cancer, treatment selection must be based on risk stratification and life expectancy: active surveillance is the preferred approach for very low and low-risk disease with life expectancy ≥10 years, while radical prostatectomy or radiation therapy are standard options for intermediate and high-risk disease. 1

Risk Stratification Framework

Treatment decisions depend critically on accurate risk classification:

• Very low risk: Gleason score ≤6, PSA <10 ng/mL, <3 positive biopsy cores, ≤50% cancer in any core, PSA density <0.15 ng/mL/g 1
• Low risk: Gleason score ≤6 and PSA <10 ng/mL 2, 1
• Intermediate risk: Gleason score 7, or PSA 10-20 ng/mL 2, 1
• High risk: Gleason score 8-10, or PSA >20 ng/mL 1

Treatment Algorithm by Risk Category and Life Expectancy

Very Low and Low-Risk Disease

For life expectancy <10 years:

• Observation (watchful waiting) is recommended, involving monitoring without immediate curative intent 2, 1
• PSA measurement and digital rectal examination at regular intervals 1
• Delayed hormone therapy only if symptomatic progression occurs 1
• This approach is supported by data showing 5-10 year cancer-specific mortality is very low for low-risk disease 2

For life expectancy ≥10 years:

• Active surveillance is the preferred option 1, 3
• Protocol includes: PSA measurement every 6 months, digital rectal examination every 12 months, repeat prostate biopsy every 12 months 1
• Intervention triggered by Gleason score progression or PSA doubling time <3 years 4
• Active surveillance achieves 99% disease-specific survival at 8 years for low-risk disease 2
• An early confirmatory biopsy (within first year) is essential to avoid underestimating tumor grade 4

Alternative curative options for low-risk disease:

• Radical prostatectomy with or without pelvic lymph node dissection (if predicted probability of lymph node involvement ≥2%) 2, 1
• External beam radiation therapy (minimum 70 Gy in 2.0 Gy fractions) 2, 1
• Brachytherapy with permanent implants 2

Intermediate-Risk Disease

For life expectancy <10 years:

• Active surveillance remains a reasonable option 2
• Only 13% of men with T0-T2 disease developed metastases 15 years after diagnosis 2

For life expectancy ≥10 years:

• Radical prostatectomy with pelvic lymph node dissection (if predicted probability of lymph node metastasis ≥2%) 2, 1
• External beam radiation therapy (3D-CRT/IMRT with daily IGRT) with or without 4-6 months of androgen deprivation therapy 2, 1
• Adding short-term ADT (4-6 months) to radiation therapy provides cancer-specific survival benefit 2
• Brachytherapy as monotherapy is NOT recommended for intermediate-risk disease, particularly with Gleason pattern 4 or 5 or PSA >10 ng/mL 2

High-Risk Disease

Standard treatment:

• Long-term ADT (2-3 years) plus radical radiation therapy is the preferred treatment based on survival benefit demonstrated in randomized controlled trials 1
• External beam radiation therapy should be delivered to a minimum target dose of 70 Gy 2
• Androgen suppression should be given before, during, and after radiotherapy for a minimum of 6 months duration 2

Comparative Effectiveness of Treatment Modalities

Radical prostatectomy vs watchful waiting:

• A randomized trial of 695 patients with early-stage prostate cancer showed radical prostatectomy improved overall survival by 5% at 10 years (73% vs 68%, P=0.04) 2
• However, these results may not be generalizable to screen-detected cancers 2

Side effect profiles differ significantly:

• Radical prostatectomy increases erectile dysfunction by 35% (80% vs 45%) and urinary leakage by 28% (49% vs 21%) compared to watchful waiting 2
• Radiation therapy has higher rates of bowel dysfunction but lower rates of incontinence and better preservation of baseline sexual function compared to surgery 2

Androgen Deprivation Therapy Considerations

For localized disease:

• ADT as primary treatment for localized prostate cancer does NOT improve survival and is not recommended 2
• ADT should only be used in combination with radiation therapy for intermediate and high-risk disease 2, 1

Medications:

• Goserelin (LHRH agonist) combined with flutamide and radiation showed significantly lower local failure rates (16% vs 33% at 4 years) compared to radiation alone in stage B2-C disease 5
• Leuprolide acts as an inhibitor of gonadotropin secretion, reducing testosterone to castrate levels within 2-4 weeks 6
• Critical caveat: Monitoring of serum testosterone is necessary with leuprolide, as insufficient androgen suppression has been documented despite continuous treatment 7

Post-Treatment Surveillance

After radical prostatectomy:

• PSA should be undetectable (<0.2 ng/mL) within 2 months 1, 3
• Measure PSA every 6-12 months for first 5 years, then annually 2, 1
• Biochemical recurrence defined as PSA ≥0.2 ng/mL on two consecutive measurements 1

After radiation therapy:

• PSA should reach ≤1.0 ng/mL within 16 months 1
• Follow same PSA monitoring schedule as post-prostatectomy 1
• Biochemical recurrence defined as PSA rise ≥2 ng/mL above nadir 1

For biochemical recurrence:

• Salvage radiation therapy to the prostate bed should be initiated early (PSA <0.5 ng/mL) for improved outcomes 1, 3

Critical Decision Points and Common Pitfalls

Avoid these errors:

• Do NOT use cryotherapy or HIFU as standard initial treatments for localized prostate cancer 3
• Do NOT diagnose "hormone-resistant prostate cancer" without confirming serum testosterone is within castration range 7
• Do NOT perform brachytherapy alone for intermediate-risk disease with Gleason pattern 4/5 or PSA >10 ng/mL 2

Essential counseling:

• Patients must consult with both a urologist and radiation oncologist before making treatment decisions 1
• Discuss treatment-related adverse effects including urinary incontinence, erectile dysfunction, and bowel dysfunction 1, 3
• More than 50% of patients significantly overestimate the survival benefit of treatment 2