What are the initial treatment options for a patient diagnosed with Gleason 3+4 prostate cancer?

Gleason 3+4 Prostate Cancer: Initial Treatment Options

For Gleason 3+4 (intermediate-risk) prostate cancer, the standard treatment options are radical prostatectomy with pelvic lymph node dissection or external beam radiation therapy (minimum 70 Gy) with or without 4-6 months of androgen deprivation therapy, with the choice depending primarily on life expectancy and patient preference after counseling about treatment-related morbidity. 1, 2

Risk Classification

Gleason 3+4 prostate cancer is classified as intermediate-risk disease by all major guideline societies 1, 2. This classification is critical because:

• Intermediate risk is defined as Gleason score 7, or PSA 10-20 ng/mL, or clinical stage T2b-T2c 3, 1
• The distinction between Gleason 3+4 versus 4+3 is prognostically significant, with 3+4 having substantially better outcomes 4
• Patients with Gleason 3+4 have a 5-year biochemical recurrence-free survival of approximately 85% compared to 60% for Gleason 4+3 4

Required Staging Workup

Before treatment selection, complete the following staging evaluation 1, 2:

• Cross-sectional imaging (CT or MRI of abdomen and pelvis) to evaluate for lymph node involvement 1
• Bone scan if PSA >10 ng/mL or if symptomatic 1
• PSA measurement and digital rectal examination 2
• Calculate predicted probability of lymph node involvement using nomograms 3

Treatment Algorithm by Life Expectancy

Life Expectancy <10 Years

Observation (watchful waiting) is the recommended approach 3, 2. This involves:

• Monitoring without immediate curative intent 2
• PSA measurement and digital rectal examination at regular intervals 3
• Delayed hormone therapy only if symptomatic progression occurs 2

Alternative options include radiation therapy or brachytherapy alone 3

Life Expectancy ≥10 Years

Active surveillance is NOT recommended for intermediate-risk disease with life expectancy >10 years 3. While some highly selected patients with Gleason 3+4 may be considered for surveillance, this remains controversial 5. The data show that patients with Gleason 3+4 at diagnosis have:

• Lower treatment-free survival (49% vs 64% for Gleason 3+3) 5
• Higher risk of biochemical recurrence after deferred surgery (31% vs 7% at 2 years) 5
• Increased likelihood of requiring treatment during surveillance 5

Standard curative treatment options include 3, 1, 2:

Option 1: Radical Prostatectomy

• Pelvic lymph node dissection should be performed if predicted probability of lymph node involvement is ≥2% 3, 1
• Lymphadenectomy should be limited to ilio-obturator regions 3
• Expected outcomes: PSA should be undetectable (<0.2 ng/mL) within 2 months 2, 6
• Counseling required regarding permanent erectile dysfunction and urinary incontinence (should be <5% requiring >2 pads daily at 1 year) 3

Option 2: External Beam Radiation Therapy

• Minimum dose of 70 Gy using 3D conformal techniques in 2.0 Gy fractions 3, 2
• Androgen deprivation therapy (ADT) for 4-6 months may be added 3, 1
• The combination of radiation plus short-term ADT improves local control and reduces disease progression in intermediate-risk disease 3
• Expected outcomes: PSA should reach ≤1.0 ng/mL within 16 months 3, 2
• Severe late complications (bladder/rectal) should be <5% at 2 years 3

Option 3: Brachytherapy Alone

• May be considered for favorable intermediate-risk patients only (single intermediate-risk factor, low tumor volume) 3
• Contraindicated in patients with obstructive urinary symptoms as it can exacerbate obstruction 2

Critical Decision Points

When to Add ADT to Radiation

Consider adding 4-6 months of ADT to radiation therapy if 3, 1:

• Multiple intermediate-risk factors present
• Higher PSA within the 10-20 ng/mL range
• Greater tumor volume on biopsy
• Patient preference after counseling about sexual dysfunction risks 2

Pelvic Lymph Node Dissection Indications

Perform pelvic lymph node dissection at radical prostatectomy if 3:

• Predicted probability of lymph node involvement ≥2% by nomogram
• May be omitted only if stage T1, Gleason score <6, and PSA <10 ng/mL 3

Important Caveats and Pitfalls

Avoid these common errors:

• Do not use primary ADT alone for localized intermediate-risk disease—it does not improve survival 3, 2
• Do not recommend cryotherapy or HIFU as standard initial treatment due to lack of long-term comparative data 3, 2
• Do not assume all Gleason 7 is the same—approximately 24% of biopsy Gleason 3+4 will be upgraded to 4+3 or higher at prostatectomy, while 47% of biopsy 4+3 will be downgraded 7
• Do not use brachytherapy in patients with significant lower urinary tract symptoms 2

Multidisciplinary Consultation

Patients must consult with both a urologist and radiation oncologist before making treatment decisions 1, 2. Counseling should include:

• Treatment-related adverse effects (incontinence, erectile dysfunction, bowel dysfunction) 1, 2
• Expected recovery timelines
• Impact on quality of life
• Salvage treatment options if initial therapy fails 1

Post-Treatment Surveillance

After Radical Prostatectomy

• PSA every 3 months during year 1, then every 6 months for 7 years 6
• Digital rectal examination optional if PSA remains undetectable 6
• Biochemical recurrence defined as PSA ≥0.2 ng/mL on two consecutive measurements 1

After Radiation Therapy

• PSA every 6 months for first 5 years, then annually 1
• Biochemical recurrence defined as PSA rise ≥2 ng/mL above nadir 1
• Consider salvage radiation to prostate bed if PSA rises after surgery (best outcomes when PSA <0.5 ng/mL) 1, 6