In a 57‑year‑old man with a PSA of 17 ng/mL and a PI‑RADS 5 peripheral‑zone lesion, can we proceed directly to radical prostatectomy?

Can We Proceed Directly to Radical Prostatectomy?

No, you should not proceed directly to radical prostatectomy in this patient without first obtaining a tissue diagnosis via prostate biopsy. A PI-RADS 5 lesion with PSA 17 ng/mL strongly suggests high-risk prostate cancer, but histologic confirmation with Gleason grading is mandatory before definitive treatment planning. 1

Why Biopsy is Required Before Surgery

• Gleason score is essential for risk stratification and treatment selection. The distinction between Gleason 3+4=7 versus 4+3=7 versus 8-10 has profound implications for whether surgery alone is appropriate or whether multimodal therapy (surgery plus adjuvant radiation) will be needed. 2, 3

• Staging imaging depends on the biopsy result. Once you have the Gleason score, you must obtain bone scintigraphy (mandatory for Gleason ≥8 or PSA >20 ng/mL) and pelvic cross-sectional imaging (CT or MRI) to rule out metastatic disease before proceeding with curative-intent surgery. 4, 3

• PSMA PET/CT should be strongly considered if available for all high-risk patients, as it provides 27% greater accuracy than conventional imaging and changes management in 28% of cases by detecting occult metastases. 4

Treatment Algorithm After Biopsy Confirmation

If Biopsy Shows Intermediate-Risk Disease (Gleason 7, PSA 10-20 ng/mL):

• Radical prostatectomy is a standard option alongside external beam radiation therapy plus short-term ADT (4-6 months) or brachytherapy. 1

• Discuss pelvic lymph node dissection using nomogram-based risk estimates, as intermediate-risk patients may benefit from extended PLND if nodal involvement probability exceeds 10%. 1, 4

If Biopsy Shows High-Risk Disease (Gleason 8-10, PSA >20 ng/mL, or clinical T3a):

• External beam radiation therapy plus long-term ADT (2-3 years) is the preferred treatment, achieving 91% 9-year disease-specific survival with trimodality therapy (EBRT + brachytherapy + ADT). 3

• Radical prostatectomy with extended PLND can be offered only to highly selected patients as part of potential multimodal therapy, but surgery alone achieves only 36% progression-free survival for Gleason 8-10 disease compared to 91% with radiation-based approaches. 1, 3

• If you choose surgery for high-risk disease, the patient must understand that adjuvant radiation therapy will likely be required if pathology shows seminal vesicle invasion, positive margins, or extraprostatic extension. 1

Critical Staging Steps Before Any Definitive Treatment

• Bone scan is mandatory for this patient given PSA 17 ng/mL, even if asymptomatic, as occult bone metastases are common in high-risk disease. 4, 3

• Pelvic MRI or CT is required to evaluate for lymph node involvement and local tumor extension. Any suspicious lymph node must be confirmed by biopsy before treatment planning. 4

• Digital rectal examination must distinguish T3a (extracapsular extension) from T3b-T4 (seminal vesicle or adjacent structure involvement), as this determines whether the patient is high-risk versus very high-risk and guides ADT duration. 4, 3

Common Pitfalls to Avoid

• Never proceed to surgery without histologic confirmation. Even a PI-RADS 5 lesion has a false-positive rate, and you cannot counsel the patient on risks/benefits or plan adjuvant therapy without knowing the Gleason score. 1

• Do not skip staging imaging. If bone scan or PSMA PET reveals metastatic disease, surgery is contraindicated and the patient requires systemic therapy (ADT plus abiraterone, apalutamide, or enzalutamide). 4, 3

• Brachytherapy monotherapy is absolutely contraindicated if biopsy confirms high-risk features (Gleason ≥8 or PSA >20 ng/mL), as it is inferior to EBRT or surgery. 3

• If surgery is performed for high-risk disease and pathology shows adverse features (pT3, positive margins, Gleason 8-10), adjuvant radiation therapy must be offered, as it reduces biochemical recurrence, local recurrence, and clinical progression. 1

Functional Outcomes the Patient Must Understand

• Erectile dysfunction occurs in approximately 80% of men after radical prostatectomy versus 45% with watchful waiting, representing a 35% absolute increase. 2

• Urinary incontinence (any leakage) develops in about 49% after surgery versus 21% with observation, an absolute increase of 28%. 2

• These toxicity rates may be lower at high-volume surgical centers, but the patient must be counseled that functional outcomes are less predictable than oncologic outcomes. 1, 2