What is the treatment for early-stage prostate cancer?

Treatment of Early-Stage Prostate Cancer

For early-stage prostate cancer, treatment selection depends primarily on risk stratification and life expectancy: very low-risk disease with <20 years life expectancy should undergo active surveillance; low-risk disease with ≥10 years life expectancy can choose between active surveillance, radical prostatectomy, or radiation therapy; intermediate and high-risk disease with ≥10 years life expectancy requires definitive treatment with either radical prostatectomy or radiation therapy (often combined with androgen deprivation therapy for intermediate-risk cases). 1

Risk Stratification Framework

Early-stage prostate cancer is categorized into distinct risk groups that determine treatment approach 1:

• Very low-risk: Clinical stage T1c, 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: Clinical stage T1-T2a, Gleason score 2-6, PSA <10 ng/mL 1
• Intermediate-risk: Clinical stage T2b-T2c OR Gleason score 7 OR PSA 10-20 ng/mL 1
• High-risk: Clinical stage T3a OR Gleason score 8-10 OR PSA >20 ng/mL 1, 2

Treatment Options by Risk Category

Very Low-Risk Disease

Active surveillance is the recommended approach for men with very low-risk disease and life expectancy <20 years. 1 This strategy involves:

• PSA testing every 3-6 months for the first 5 years, then annually 2
• Digital rectal examination every 6-12 months 2
• Confirmatory prostate biopsy at 12-24 months after initial diagnosis 1, 3, 4
• Repeat biopsies based on PSA velocity (>0.75 ng/mL/year triggers concern) 3

The rationale is compelling: prostate cancer-specific mortality at 5-10 years is very low for most early-stage cancers, and definitive treatment can be reserved for progression 1. In contemporary series, disease-specific survival with active surveillance approaches 100% with median follow-up of 3.6 years 3.

Low-Risk Disease with ≥10 Years Life Expectancy

Three equivalent options exist: active surveillance, radical prostatectomy, or radiation therapy. 1 The choice depends on patient preference regarding side effect profiles:

Radical prostatectomy 1:

• Pelvic lymph node dissection should be performed if predicted probability of lymph node involvement is ≥2% 1
• The Scandinavian Prostate Cancer Group Study 4 demonstrated that radical prostatectomy reduced prostate cancer death risk from 29% to 18% at 18 years compared to watchful waiting (P=0.001) 1
• Higher rates of urinary incontinence (49% vs 21%) and erectile dysfunction (80% vs 45%) compared to watchful waiting 1
• Lower rates of bowel dysfunction compared to radiation therapy 1

Radiation therapy 1:

• Options include 3D-conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT) with daily image-guided radiation therapy (IGRT), or brachytherapy 1
• Similar long-term erectile dysfunction rates to surgery but higher bowel dysfunction rates 1
• Lower short-term erectile dysfunction compared to surgery 1

Active surveillance remains appropriate for low-risk patients who prefer to avoid immediate treatment side effects, using the monitoring protocol described above 1, 4, 5.

Intermediate-Risk Disease with ≥10 Years Life Expectancy

Definitive treatment is recommended; active surveillance is NOT recommended for unfavorable intermediate-risk disease. 1 Treatment options include:

Radiation therapy with short-term androgen deprivation therapy (ADT) 1:

• External beam radiation therapy (EBRT) ± 4-6 months of ADT ± brachytherapy boost 1
• Brachytherapy alone is an option for favorable intermediate-risk cases 1

Radical prostatectomy 1:

• With pelvic lymph node dissection if predicted probability of lymph node metastasis ≥2% 1
• For patients with favorable intermediate-risk features (Gleason 3+4=7, <50% positive cores, only one intermediate-risk factor), active surveillance may be considered 1

Important distinction: Patients with favorable intermediate-risk (predominantly Gleason grade 3, <50% positive cores, only one NCCN intermediate-risk factor) may be considered for active surveillance, but this is not appropriate for unfavorable intermediate-risk disease 1.

High-Risk Localized Disease

Combination therapy with radiation plus long-term ADT is the standard approach. 2

• External beam radiation therapy combined with 2-3 years of ADT 2
• RTOG 92-02 demonstrated superior outcomes with long-term (2+ years) versus short-term (4 months) ADT, particularly for Gleason 8-10 disease (overall survival 45% vs 32%, P=0.0061) 2
• EORTC 22961 confirmed superior survival when 2.5 years of ADT was added to radiation therapy 2

Critical Treatment Considerations

Androgen Deprivation Therapy Limitations

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

Cryotherapy Status

Cryosurgery is not recommended as primary therapy due to lack of long-term comparative data with surgery and radiation. 1 While 5-year biochemical disease-free rates range from 65-92% in low-risk patients, insufficient evidence exists to recommend it over established treatments 1.

Active Surveillance Progression Triggers

Criteria for transitioning from active surveillance to active treatment include 3, 4:

• Increase in Gleason score on repeat biopsy (most common trigger, 27-100% of treated patients) 4
• PSA doubling time <3 years (13-48% of treated patients) 4
• Patient preference (7-13% receive treatment with no evidence of progression) 4

Common Pitfalls to Avoid

Do not rely on initial biopsy alone: Up to 38% of patients on active surveillance have higher-grade disease on repeat biopsy 3. A confirmatory biopsy at 12-24 months is essential to avoid underestimating tumor grade 4.

Do not screen men >70 years: Testing for prostate cancer in asymptomatic men should not be done in men over age 70 1.

Do not use PSA screening without informed consent: Population-based PSA screening reduces prostate cancer mortality but causes overdiagnosis and overtreatment; screening should only occur after discussing potential benefits and harms 1.

Treatment Decision-Making Process

The algorithmic approach is:

1. Confirm diagnosis and risk category using clinical stage, Gleason score, and PSA level 1
2. Assess life expectancy using age and comorbidities 1
3. For life expectancy <10 years: Watchful waiting regardless of risk category 1
4. For life expectancy ≥10 years: Match treatment intensity to risk category as outlined above 1
5. Ensure multidisciplinary consultation: Men should consult both urologist and radiation oncologist before deciding 1
6. Counsel on side effects: Treatment causes sexual dysfunction, infertility, bowel problems, and urinary issues 1

The treatment landscape has evolved significantly, with approximately 75% of prostate cancers now detected at localized stages where 5-year survival approaches 100% 6. This shift emphasizes the importance of appropriate risk stratification to avoid overtreatment while ensuring aggressive cancers receive definitive therapy.