What are the management options for carcinoma of the prostate?

Management of Carcinoma Prostate

Management of prostate cancer must be stratified by risk category, with treatment decisions based on PSA level, Gleason score, clinical stage, and life expectancy—not simply patient age. 1

Risk Stratification Framework

Before selecting treatment, classify patients into risk categories using these criteria 1:

• Low risk: PSA <10 ng/mL AND Gleason score ≤6 AND clinical stage ≤T2a
• Intermediate risk: PSA 10-20 ng/mL OR Gleason score 7 OR clinical stage T2b (but not meeting high-risk criteria)
• High risk: PSA >20 ng/mL OR Gleason score 8-10 OR clinical stage ≥T2c

Clinical tumor stage, Gleason score, and pretreatment PSA are the primary prognostic factors that determine appropriate treatment strategy. 1, 2

Management by Risk Category

Low-Risk Disease

For low-risk localized prostate cancer, active surveillance, interstitial brachytherapy, external beam radiation therapy (EBRT), and radical prostatectomy are all appropriate monotherapy options. 1, 2

Active surveillance is particularly appropriate for patients with low-risk disease, as it has demonstrated 99% disease-specific survival at 8 years. 2 This approach involves:

• Regular PSA and digital rectal examination monitoring 1
• Repeat prostate biopsies to detect progression 1
• Intervention only when evidence of tumor progression appears 1

Active surveillance is best suited for men with shorter life expectancy (<10 years) or those with very small cancer volumes who wish to avoid treatment side effects. 1

Radical prostatectomy is the standard treatment for patients with stage T1a, T1b, T1c, or T2 prostate cancer who have life expectancy >10 years and accept treatment-related complications. 2 Based on randomized controlled trial data, radical prostatectomy may be associated with lower risk of cancer recurrence and cancer-related death compared to watchful waiting. 1

EBRT should be delivered using conformal techniques to a minimum target dose of 70 Gy given in 2.0 Gy fractions or equivalent. 2 Conformal radiotherapy reduces late toxicity compared with conventional radiotherapy. 2

Brachytherapy is an option for low-risk patients, with iridium as the standard isotope for temporary implants. 2

Intermediate-Risk Disease

Active surveillance, interstitial brachytherapy, EBRT, and radical prostatectomy are all appropriate treatment options for intermediate-risk localized prostate cancer. 1

Patient preferences regarding urinary, sexual, and bowel function should guide treatment selection, as different modalities have varying side effect profiles. 1

For patients considering EBRT, the use of adjuvant and concurrent hormonal therapy may prolong survival based on randomized controlled trial evidence. 1

High-Risk Disease

High-risk patients who choose EBRT should receive combined hormone therapy (for at least 2 years) with 3D radiation therapy, as this combination has been shown to prolong survival in randomized controlled trials. 1, 2

When comparing watchful waiting to radical prostatectomy in high-risk patients, radical prostatectomy may lower the risk of cancer recurrence and improve survival. 1

While active surveillance, brachytherapy, EBRT, and radical prostatectomy remain options for high-risk disease, recurrence rates are high with any single modality. 1 Despite lack of definitive evidence of superiority among treatments, the high risk of disease progression and death makes active treatment generally preferred over surveillance in this population. 1

Locally Advanced Disease (Stage T3)

External beam radiotherapy combined with hormone therapy is the standard treatment for locally advanced disease. 2

For Stage T2b-T4 (Stage B2-C) prostatic carcinoma, goserelin (ZOLADEX) in combination with flutamide should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy. 3

Metastatic Disease

Androgen deprivation therapy (ADT) through surgical castration (bilateral orchiectomy) or medical castration (LHRH agonists like goserelin) is the standard first-line treatment for metastatic prostate cancer. 1, 3

When starting LHRH agonist therapy, an antiandrogen should be given for 3-4 weeks initially to prevent testosterone flare. 1

Combined androgen blockade (medical castration plus antiandrogen) may provide a small survival benefit but with increased toxicity. 1 Patients willing to accept increased toxicity for this small survival benefit should be offered a nonsteroidal antiandrogen in addition to castrate therapy. 1

For castration-resistant prostate cancer (CRPC), abiraterone acetate is indicated at 1,000 mg once daily (taken at least 1 hour before or 2 hours after food) in combination with prednisone 5 mg twice daily. 4 Abiraterone inhibits CYP17, blocking androgen biosynthesis in testicular, adrenal, and prostatic tumor tissues. 4

Special Populations

Patients with Life Expectancy <10 Years

For patients with stage T1c or T2 prostate cancer and life expectancy <10 years, a watchful waiting policy should be considered, particularly for lower stage and grade disease. 1

Watchful waiting involves forgoing definitive treatment initially and providing palliative treatment only if local or metastatic progression occurs. 1 This may include transurethral resection for urinary obstruction or hormonal therapy/radiotherapy for metastatic lesions. 1

Stage T1a or T1b Disease

For patients with life expectancy >10 years, two options exist: primary curative treatment or re-evaluation of the remaining prostate to confirm residual tumor. 1 The remaining prostate should be biopsied if postoperative digital rectal examination is abnormal and/or 3-month postoperative PSA is >4 ng/mL or reduced by <50%. 1

Monitoring and Follow-Up

The criterion for progression after radical prostatectomy, external-beam radiotherapy, or brachytherapy is an increase in PSA concentration measured on three successive occasions at monthly intervals. 1

Following radical prostatectomy, the criterion for complete remission is an undetectable PSA concentration (under 0.1 ng/mL) for at least 7 years. 1 Patients should be monitored with a sensitive PSA assay, with salvage radiotherapy to the prostate bed given in the event of PSA failure. 2

A minimum 15-year follow-up is necessary to evaluate the efficacy of treatment for localized prostate cancer, with 10-year metastasis-free survival as an acceptable intermediate criterion. 1

Critical Staging Investigations

Digital rectal examination and transrectal ultrasound should be performed prior to biopsies. 1

Abdominal and pelvic CT scan should be performed in patients with T2a stage disease or higher, PSA >15 ng/mL, and Gleason score ≥7. 1

Bone scan should be performed in the presence of bone pain, locally advanced prostatic lesion (≥T3Nx or T1-4N1-3), presence of Gleason grade 4 or 5, and PSA ≥10 ng/mL. 1

Common Pitfalls

The great disparity between prostate cancer incidence and mortality indicates many men may not benefit from definitive treatment—autopsy studies show 60-70% of older men have prostate cancer, yet only 3% die from it. 1 This underscores the importance of risk stratification rather than treating all diagnosed cancers aggressively.

Life expectancy, not chronological age, should drive treatment decisions. 1 Older men with high-risk disease are more likely to die from prostate cancer than younger men and should not be undertreated based solely on age. 5

Patient preferences regarding functional outcomes (urinary, sexual, bowel function) must be incorporated into decision-making, as no single treatment is optimal for all patients. 1