What is the appropriate adjuvant treatment for a patient after radical prostatectomy with a dominant prostate cancer nodule composed of ~40% Gleason pattern 3 and ~60% Gleason pattern 4, non‑focal extraprostatic extension into the left neurovascular bundle, and negative surgical margins?

Pathology Interpretation and Treatment Recommendation

This pathology report describes a Gleason 4+3=7 (ISUP Grade Group 3) prostate cancer with extraprostatic extension (pT3a) and negative surgical margins—you should offer adjuvant radiotherapy to the prostate bed within the next year, ideally before PSA exceeds 0.2 ng/mL, with consideration of short-term androgen deprivation therapy (ADT) for 4-6 months given the Gleason 4+3 pattern. 1, 2

Understanding the Pathology

Your pathology shows several important adverse features:

• Gleason 4+3=7: This means 60% of the tumor is the more aggressive pattern 4, with 40% pattern 3. This is biologically distinct from Gleason 3+4=7 and carries significantly worse prognosis 3, 4, 5
• Extraprostatic extension (EPE): The cancer has grown through the prostate capsule into the left neurovascular bundle, making this pT3a disease 1
• Non-focal EPE: The "non-focal" descriptor indicates this is not just microscopic extension, which is a higher-risk feature 1
• Negative margins: Fortunately, the surgeon achieved complete excision with no cancer at the cut edges 1

Primary Treatment Recommendation: Adjuvant Radiotherapy

The strongest evidence supports offering adjuvant radiotherapy based on your adverse pathologic features (extraprostatic extension, Gleason 4+3=7). 1, 2

Why Radiotherapy is Recommended

Multiple randomized controlled trials demonstrate that adjuvant RT improves outcomes for patients like you:

• SWOG 8794 showed improved 10-year biochemical failure-free survival for high-risk patients (36% vs 12%, P=0.001) and ultimately demonstrated improved overall survival and metastasis-free survival 1, 2
• EORTC trial demonstrated 5-year biochemical progression-free survival improvement (78% vs 49%) for patients with positive margins or EPE 1
• German ARO 96-02 trial showed improved 5-year biochemical progression-free survival (72% vs 54%, HR 0.53) for pT3 disease with undetectable PSA 1, 2

Radiation Therapy Specifications

• Timing: Should be delivered within 1 year after surgery, once surgical side effects have stabilized 1, 2
• Dose: 64-70 Gy in standard fractionation to the prostate bed 1
• Technique: Use IMRT/VMAT with image-guided radiotherapy (IGRT) 1
• Target: Prostate bed; pelvic lymph nodes are optional and not mandatory in your case 1

Role of Androgen Deprivation Therapy (ADT)

ADT alone without radiation has NO role in your situation since you are node-negative (pN0). 2 However, short-term ADT (4-6 months) combined with adjuvant radiation may be considered given your Gleason 4+3 pattern, though this recommendation is primarily extrapolated from primary radiation data rather than post-prostatectomy trials. 1, 2

Critical Distinction to Understand

• ADT is NOT recommended as monotherapy for node-negative pT3 disease after prostatectomy 2
• ADT may be added to radiation for intermediate-to-high risk features like Gleason 4+3=7 1
• ADT is definitively indicated only if lymph nodes were positive (which yours were not) 2

Alternative Approach: Observation with Early Salvage RT

Some patients and physicians prefer observation with close PSA monitoring, planning for salvage radiotherapy if PSA becomes detectable. 1

If Choosing Observation

• Monitor PSA every 3-6 months 1
• Salvage RT is most effective when PSA is <0.5-1.0 ng/mL 1
• Consider salvage RT if PSA becomes detectable and rises on 2 subsequent measurements 1

However, the trade-off is clear: adjuvant RT reduces biochemical recurrence, local recurrence, and clinical progression more effectively than waiting for PSA rise. 1 The impact on metastasis and overall survival is less certain, with one trial showing benefit and another not demonstrating clear survival advantage. 1

Why Gleason 4+3 Matters

The predominance of pattern 4 (60%) versus pattern 3 (40%) is prognostically significant:

• Gleason 4+3 has 5-year progression rates of 40% compared to 15% for Gleason 3+4 5
• Gleason 4+3 independently predicts biochemical recurrence (HR 1.43, p<0.001) 6
• Gleason 4+3 correlates with more advanced pathological stage and higher risk of metastatic disease 3, 4, 5

Common Pitfalls to Avoid

• Do not delay treatment indefinitely: If choosing adjuvant RT, it should be delivered within 1 year and ideally before PSA exceeds 1.5 ng/mL 1
• Do not use ADT alone: ADT monotherapy without radiation does not improve survival in node-negative disease 2
• Do not assume all Gleason 7 is the same: Your 4+3 pattern carries significantly worse prognosis than 3+4 3, 4, 5
• Do not ignore the non-focal EPE: This is a high-risk feature that strengthens the indication for adjuvant therapy 1

Recommended Discussion with Your Oncologist

You should discuss:

1. Adjuvant RT to prostate bed (64-70 Gy) starting within the next few months 1
2. Addition of short-term ADT (4-6 months) to the radiation, given your Gleason 4+3 pattern 1
3. Alternative of observation with early salvage RT if PSA becomes detectable, understanding this may result in higher recurrence rates 1
4. Potential side effects of radiation (urinary, bowel, sexual function) versus risk of cancer recurrence without treatment 1

The most recent high-quality guidelines from the EAU (2024) and NCCN (2014) both strongly support adjuvant radiotherapy for patients with your pathologic features. 1, 2