Prostate Cancer Treatment
Treatment Selection by Risk Category and Life Expectancy
For localized prostate cancer, treatment must be stratified by risk category (low, intermediate, high) and life expectancy, with active surveillance for low-risk disease in men with ≥10 years life expectancy, radical prostatectomy or radiotherapy (with or without ADT) for intermediate and high-risk disease in healthy men, and watchful waiting for those with <10 years life expectancy. 1
Low-Risk Localized Disease
Definition
Treatment Options Based on Life Expectancy
Life expectancy ≥10 years:
- Active surveillance is the preferred option, including PSA measurement every 6 months, digital rectal examination every 12 months, and repeat prostate biopsy every 12 months 2, 3
- Alternative curative options include radical prostatectomy, external beam radiation therapy (EBRT ≥70 Gy), or brachytherapy (≥120 Gy palladium or ≥140 Gy I-125) 1, 2, 3
- Active surveillance avoids treatment-related morbidity while maintaining the option for curative intervention if disease progresses 2
Life expectancy <10 years:
- Watchful waiting (observation) is recommended, involving monitoring without immediate curative intent, with delayed hormone therapy only if symptomatic progression occurs 2, 3
- The "10-year rule" applies: patients should only be treated if comorbidity-adjusted life expectancy is at least 10 years 1
Critical Caveat
- For men with well-differentiated tumors, potentially curative therapy prolonged life expectancy up to age 75 years but did not improve quality-adjusted life expectancy at any age 4
- Treatment of low-risk disease in men over 70 years generally appears harmful 5
Intermediate-Risk Localized Disease
Definition
- PSA 10-20 ng/mL or Gleason score 7, clinical stage T2b-T2c 1, 2
- Subdivided into favorable (Gleason 3+4) and unfavorable (Gleason 4+3) intermediate risk 1
Treatment Options
Standard treatment (Strong Recommendation):
- Radical prostatectomy with pelvic lymph node dissection 1, 2
- External beam radiotherapy (minimum 70 Gy) plus androgen deprivation therapy (ADT) for 4-6 months 1, 2
Favorable intermediate risk:
- Radiation therapy alone may be used, but the evidence basis is less robust than combining radiotherapy with ADT 1
- Active surveillance may be offered to select patients with favorable intermediate risk, but patients must be informed this comes with higher risk of developing metastases compared to definitive treatment 1
Unfavorable intermediate risk:
- Staging with cross-sectional imaging (CT or MRI) and bone scan should be considered 1
Life expectancy ≤5 years:
- Observation or watchful waiting is recommended 1
Alternative Options
- Cryosurgery may be considered in select patients depending on patient-specific factors, preferences, comorbidities, and life expectancy 1
- Brachytherapy is an acceptable option for intermediate-risk disease 1, 3
Critical Caveats
- Focal therapy and HIFU are not standard care options because comparative outcome evidence is lacking 1
- For moderately differentiated cancers, potentially curative therapy resulted in life expectancy and quality-adjusted life expectancy gains up to age 75 years 4
High-Risk Localized Disease
Definition
Treatment Options (Strong Recommendation)
Standard treatment:
- External beam radiotherapy (minimum 70 Gy) plus long-term ADT for 2-3 years 1, 3
- Radical prostatectomy with extended pelvic lymph node dissection 1, 3
Staging Requirements
- Patients with high-risk disease should be staged for metastases using CT (chest, abdomen, pelvis) and bone scan 1
Critical Caveats
- Active surveillance is not recommended for high-risk localized prostate cancer 1
- Watchful waiting should only be considered in asymptomatic men with limited life expectancy (≤5 years) 1
- Cryosurgery, focal therapy, and HIFU are not recommended for high-risk localized prostate cancer outside of clinical trials 1
- Primary ADT alone should not be used for localized prostate cancer as it does not improve survival 3
- For poorly differentiated disease, potentially curative therapy resulted in life expectancy and quality-adjusted life expectancy gains up to age 80 years 4
Metastatic Hormone-Sensitive Prostate Cancer
First-Line Treatment (Strong Recommendation)
Standard treatment:
- Continuous ADT (bilateral orchiectomy or LHRH agonists) plus novel androgen receptor pathway inhibitors 1, 2, 6
- Abiraterone plus ADT improved median overall survival from 36.5 months to 53.3 months (HR 0.66,95% CI 0.56-0.78) compared with medical castration alone 6
- Alternative androgen receptor pathway inhibitors include enzalutamide, apalutamide, or darolutamide 1, 6
For patients fit enough for chemotherapy:
- ADT plus docetaxel provides survival benefit and represents a paradigm shift from sequential therapy 1, 2
- Docetaxel 75 mg/m² every 3 weeks demonstrated statistically significant overall survival advantage (median 18.9 months vs 16.5 months, HR 0.761, p=0.0094) 7
For frail patients:
- ADT alone is appropriate for patients who cannot tolerate combination therapy 1
Supportive Care
- Men starting ADT should be informed that regular exercise reduces fatigue and improves quality of life 1
- Patients on long-term ADT should be monitored for osteoporosis and metabolic syndrome 2
- Bone health agents should be considered 1
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
First-Line Treatment Options
- Abiraterone 1
- Enzalutamide 1
- Docetaxel (75 mg/m² every 3 weeks) 1, 7
- Radium-223 for patients unfit for above treatments with bone-only metastases 1
Second-Line or Post-Docetaxel Options
Post-Treatment Surveillance and Salvage Therapy
After Radical Prostatectomy
- PSA should be undetectable (<0.2 ng/mL) within 2 months after surgery 2, 3
- Follow-up includes PSA measurement every 3 months during year 1, then every 6 months for 7 years 2
- Biochemical recurrence is defined as confirmed PSA >0.2 ng/mL 2
After Radiotherapy
- PSA should reach ≤1 ng/mL within 16 months after completing radiotherapy 2, 3
- Biochemical recurrence is defined as nadir PSA plus 2 ng/mL 2
Salvage Radiotherapy
- For biochemical recurrence after radical prostatectomy, salvage radiotherapy to the prostate bed should be initiated early (PSA <0.5 ng/mL) 1, 2, 3
- Early salvage radiotherapy improves outcomes compared to delayed treatment 2
Management of Biochemical Relapse
- Early ADT is not routinely recommended for men with biochemical relapse unless they have symptomatic local disease, proven metastases, or PSA doubling time <3 months 1
- Intermittent ADT is recommended for men with biochemical relapse after radical radiotherapy starting ADT 1
Adverse Effects by Treatment Modality (at 2 Years)
Radical Prostatectomy
- Erectile dysfunction (no erections at all): 58% 1
- Urinary incontinence (leaking): 35% 1
- Bowel problems (urgency): 14% 1
- Older men experience higher rates of permanent erectile dysfunction and urinary incontinence compared to younger men 3
External Beam Radiation
Hormone Therapy (ADT)
- Erectile dysfunction: 86% 1
- Associated with gynecomastia 1
- Increased risk of osteoporosis and metabolic syndrome 2
Watchful Waiting
Comorbidity-Adjusted Life Expectancy
Assessment Tool
- Use the Charlson Comorbidity Index to estimate comorbidity-adjusted life expectancy 1, 8
- Age alone is not accurate in estimating life expectancy 1
- The number of comorbid diseases is the most significant predictor of survival after treatment of prostate cancer 1
Life Expectancy by Health Quartile (Examples)
- Age 65, top quartile (no disease): 25.0 years 1
- Age 65, middle quartiles (1-2 diseases): 16.67 years 1
- Age 65, bottom quartile (≥3 diseases): 8.33 years 1
- Age 75, top quartile: 15.36 years 1
- Age 75, middle quartiles: 10.24 years 1
- Age 75, bottom quartile: 5.12 years 1
Clinical Application
- Benefits of potentially curative therapy are restricted to men with no worse than mild comorbidity 4
- Comorbidity and life expectancy impact treatment tolerance and the likelihood of benefiting from aggressive cancer treatment 9
Common Pitfalls to Avoid
- Never use primary ADT alone for non-metastatic disease as it does not improve survival 1, 3
- Never recommend cryotherapy, HIFU, or focal therapy as standard initial treatments for localized prostate cancer 1, 3
- Never use hormone therapy as adjunct to surgery in low-risk patients because it does not increase treatment effectiveness and is associated with gynecomastia and erectile dysfunction 1
- Never recommend active surveillance for high-risk localized prostate cancer 1
- Never deny radical local treatment solely because metastatic lesions are identified on novel imaging techniques (PSMA-PET, whole-body MRI) in patients with localized disease on routine imaging 1
- Never perform vigorous prostatic massage in patients being evaluated for prostate cancer 10
- Brachytherapy can exacerbate urinary obstructive symptoms 3
- Older men are at risk for both overtreatment of low-risk disease and undertreatment of high-risk disease 9