Prostate Cancer
Prostate cancer represents the most common non-cutaneous malignancy in men worldwide, accounting for approximately 15% of all male cancers. It originates from the glandular epithelium of the prostate gland, typically arising in the peripheral zone. The disease spectrum ranges from indolent, organ-confined tumors that may never cause clinical symptoms to aggressive, metastatic cancers with significant morbidity and mortality.
Clinical Pearls
Adenocarcinoma Dominance: >95% of prostate cancers are adenocarcinomas arising from the acinar glands of the peripheral zone (70%).
The "Braking" Gene: BRCA2 mutations confer the highest risk (8.6-fold) and are associated with earlier onset, more aggressive disease, and poorer outcomes.
Metastatic Patterns: Prostate cancer loves bone. Osteoblastic (sclerotic) metastases to the axial skeleton (spine, pelvis) are the hallmark. Lytic lesions are rare.
PSA Velocity: An absolute rise of >0.75 ng/mL/year (in patients with PSA 4-10) is a strong predictor of malignancy, even if the absolute value is "normal" for age.
Red Flags:
- Lower urinary tract symptoms in men >50 years (urgency, frequency, nocturia- Hematospermia or hemospermia
- Bone pain suggesting metastatic disease
- Unexplained weight loss or fatigue
Risk Factors:
Non-Modifiable Risk Factors:
- Age: Risk increases exponentially after age 50
- Race/Ethnicity: African-American men highest risk, Asian men lowest
- Family History: First-degree relative increases risk 2-3 fold
- Genetic Factors: BRCA2 mutations (8.6-fold risk, HOXB13 mutations
Modifiable Risk Factors:
- Diet: High red meat/fat intake increases risk, Mediterranean diet protective
- Obesity: BMI >30 associated with 15-20% increased risk
- Physical Activity: Regular exercise reduces risk by 10-20%
- Smoking: 20-30% increased risk, worse prognosis
Protective Factors:
- 5α-reductase inhibitors (finasteride/dutasteride reduce risk by 25%
- Vitamin D sufficiency
- Plant-based diets rich in lycopene and selenium
- Regular screening and early detection
Prostate cancer exhibits significant geographic and ethnic variation in incidence and mortality. The global burden continues to rise due to aging populations and improved detection methods.
Key Statistics:
- Global incidence: ~1.4 million new cases annually (2020- Age-standardized incidence rate: 29.3 per 100,000 men
- Lifetime risk: 1 in 8 men will develop prostate cancer
- Peak incidence: 65-74 years, median age at diagnosis: 66 years
Mortality Trends:
- Age-standardized mortality rate: 7.7 per 100,000 men globally
- Accounts for ~6.8% of male cancer deaths worldwide
- Declining mortality rates in high-income countries due to screening and treatment advances
- Higher mortality in low- and middle-income countries due to limited access to care
Geographic Variation:
- Highest incidence: Northern/Western Europe, North America, Australia
- Lowest incidence: South-Central Asia, Northern Africa
- Mortality disparities largely reflect differences in healthcare access and screening practices
Prostate cancer develops through a multi-step process involving genetic and epigenetic alterations that disrupt normal prostate epithelial cell growth and differentiation.
Pathophysiology Steps
Step 1: Initiation and Genomic Alterations
- Genetic Driver: Somatic mutations accumulate in luminal epithelial cells. The most common is the TMPRSS2:ERG gene fusion (approx. 50% of cases), which puts the ERG oncogene under the control of an androgen-responsive promoter.
- Tumor Suppressors: Inactivation of PTEN, TP53, and RB1 loss accelerates progression.
- Inflammation: Proliferative Inflammatory Atrophy (PIA) caused by oxidants/infection may be a precursor lesion.
Step 2: Prostatic Intraepithelial Neoplasia (PIN)
- Precursor: High-Grade PIN (HGPIN) consists of benign glands with cytologic atypia (nucleomegaly, hyperchromasia).
- Architecture: The basal cell layer is preserved (key distinction from carcinoma), but the basement membrane is intact.
- Microenvironment: Stromal changes begin to support angiogenesis.
Step 3: Invasive Adenocarcinoma
- Invasion: Loss of the basal cell layer and disruption of the basement membrane allows invasion into the prostatic stroma.
- Dependency: The tumor is Androgen Dependent. Testosterone enters the cell, is converted to Dihydrotestosterone (DHT) by 5-alpha-reductase, and binds the Androgen Receptor (AR) to drive transcription of growth factors.
- Perineural Invasion: A common mechanism of extraprostatic spread, tracking along nerve sheaths.
Step 4: Local Progression & Metastasis
- Capsular Breach: Tumor extends into periprostatic fat, seminal vesicles (T3b), or adjacent organs (bladder neck/rectum - T4).
- Lymphatics: Spread to obturator and internal iliac nodes.
- Hematogenous: Spread to the axial skeleton via the Batson venous plexus.
- Osteoblastic Mets: Tumor cells secrete Endothelin-1 and Wnt proteins, stimulating osteoblasts to lay down new bone (sclerotic lesions).
Step 5: Castration Resistance (CRPC)
- Adaptation: Following Androgen Deprivation Therapy (ADT), tumor cells evolve mechanisms to survive low androgen levels.
- Mechanisms:
- AR Amplification: Making more receptors.
- Splice Variants: AR-V7 (constitutively active without ligand).
- Intratumoral Synthesis: Tumor makes its own testosterone.
- Neuroendocrine Transdifferentiation: Loss of AR dependence (aggressive).
Prostate cancer often presents asymptomatically in early stages, detected through screening. Symptomatic presentation typically indicates locally advanced or metastatic disease.
Asymptomatic (Screening-Detected:
Lower Urinary Tract Symptoms (LUTS:
Locally Advanced Disease:
Paraneoplastic Syndromes:
Digital Rectal Examination (DRE:
- Assesses prostate size, consistency, nodularity
- Abnormal findings: Hard nodules, asymmetry, induration
- Sensitivity: 50-70% for palpable tumors
- Specificity: 60-80%
General Physical Examination:
- Lymph node assessment: Supraclavicular, inguinal nodes
- Abdominal examination: Hepatomegaly, masses
- Neurological assessment: If spinal cord compression suspected
- Performance status evaluation
Specialized Assessments:
- Per rectal examination under anesthesia if indicated
- Bone tenderness assessment for metastatic evaluation
- Lower extremity edema assessment
Key Findings:
- Firm/hard prostate nodule suggests malignancy
- Asymmetrical prostate enlargement
- Loss of rectal tone may indicate advanced local disease
- CVA tenderness suggests bladder involvement
Biochemical Tests:
- Prostate-Specific Antigen (PSA: Total PSA, free PSA, PSA velocity
- PSA density: PSA/prostate volume ratio
- Age-adjusted PSA thresholds: 40-49: >2.5 ng/mL, 50-59: >3.5 ng/mL, 60-69: >4.5 ng/mL, >70: >6.5 ng/mL
Imaging Studies:
- Multiparametric MRI (mpMRI: PI-RADS scoring system for risk stratification
- Bone scintigraphy: For metastatic evaluation (sensitivity 80-90%- CT chest/abdomen/pelvis: For nodal and visceral metastases
- PET-CT (PSMA, choline: Emerging role in staging and recurrence detection
Biopsy and Pathology:
- Transrectal ultrasound-guided biopsy: 10-12 cores systematic biopsy
- MRI-targeted biopsy: For suspicious lesions
- Gleason grading system (Grade Group 1-5- Immunohistochemistry: AMACR, p63, CK903 for diagnosis confirmation
Staging Investigations:
- Bone scan for suspected metastases
- CT/MRI for local staging and nodal assessment
- PSMA PET-CT increasingly used for accurate staging
Risk Stratification Tables:
| Risk Category | PSA (ng/mL | Gleason Score | Clinical Stage | 5-year Survival |
|---|---|---|---|---|
| Low Risk | less than 10 | ≤6 | T1-T2a | 95-100% |
| Intermediate Risk | 10-20 | 7 | T2b-T2c | 85-95% |
| High Risk | >20 | 8-10 | T3a-T4 | 70-85% |
| Very High Risk | >20 | Any | T3b-T4 | 60-75% |
| Metastatic | Any | Any | Any + Mets | 30-50% |
TNM Staging System:
- T1: Clinically inapparent, detected by PSA/biopsy
- T2: Palpable, confined to prostate
- T3: Extraprostatic extension
- T4: Invasion of adjacent structures
- N1: Regional lymph node involvement
- M1: Distant metastases
Management strategy depends on risk stratification, patient preferences, comorbidities, and life expectancy. Treatment continuum ranges from active surveillance to palliative care.
PROSTATE CANCER MANAGEMENT ALGORITHM
=====================================
Patient presents with prostate cancer diagnosis
|
v
Risk Stratification (PSA, Gleason, Stage |
+-------------------+-------------------+
| | |
LOW RISK INTERMEDIATE HIGH RISK
(GG 1-2, PSAless than 10, RISK (GG 3, PSA (GG 4-5, PSA>20,
T1-T2a 10-20, T2b-T2c T3a+ or N+ | | |
Active Surveillance | Radical Prostatectomy +
(PSA q3-6 months, | ADT (2-3 years Repeat biopsy q1-2 | OR
years | External Beam RT +
| | ADT (4-6 months v v OR
Curative Intent: Curative Intent: ADT + Docetaxel
- Radical Prostatectomy - Radical Prostatectomy OR
- External Beam RT - External Beam RT Abiraterone + ADT
- Brachytherapy - Brachytherapy OR
- Active Surveillance - Consider ADT boost Enzalutamide + ADT
ALL PATIENTS
|
v
Regular PSA monitoring
(q3-6 months initially |
+-------------------+
| |
PSA STABLE PSA RISING/Biochemical Failure
| |
Continue monitoring | Assess for local vs systemic recurrence
| |
v v
Reassess at 5-10 Salvage Therapy:
years for potential - Local: Salvage RT or Prostatectomy
intervention - Systemic: ADT initiation
- Metastatic: ADT + novel agents
METASTATIC DISEASE
|
+-------------------+-------------------+
| | |
Hormone-Sensitive Castration-Resistant Non-Castrate
(mHSPC (mCRPC Resistant
| | |
ADT + Docetaxel | ADT monotherapy ADT + Abiraterone
OR ADT + Abiraterone | OR ADT + Bicalutamide OR ADT + Apalutamide
OR ADT + Enzalutamide | OR ADT + Enzalutamide
| | |
Progression --> Progression --> Progression -->
mCRPC management mCRPC management mCRPC management
mCRPC MANAGEMENT
|
+-------------------+-------------------+
| | |
Chemotherapy Naïve Prior Chemotherapy BRCA+ or HRR+
| | |
Abiraterone + Prednisone | Cabazitaxel Olaparib
OR Enzalutamide | OR Abiraterone OR Rucaparib
OR Docetaxel | OR Enzalutamide OR Niraparib
| |
Progression --> Progression -->
Cabazitaxel Radium-223 + Best SOC
OR Radium-223 OR Sipuleucel-T
OR Clinical trials OR Clinical trials
PALLIATIVE CARE
|
v
Pain management, SRE prevention
Psychological support, hospice care
End-of-life discussions
Active Surveillance Protocol:
- PSA every 3-6 months
- DRE annually
- Repeat biopsy at 1-2 years, then every 3-5 years
- MRI surveillance for higher-risk patients
Curative Treatment Options:
- Radical Prostatectomy: Open, laparoscopic, robotic-assisted
- External Beam Radiotherapy: IMRT/VMAT, stereotactic body RT
- Brachytherapy: LDR (I-125 seeds or HDR
- Combination approaches for intermediate/high-risk disease
Systemic Therapies:
- Androgen Deprivation Therapy (ADT: LHRH agonists/antagonists, bilateral orchiectomy
- Anti-androgens: Bicalutamide, flutamide
- Novel hormonal agents: Abiraterone, enzalutamide, apalutamide, darolutamide
- Chemotherapy: Docetaxel, cabazitaxel
- Immunotherapy: Sipuleucel-T
- Bone-targeted therapy: Denosumab, zoledronic acid
Metastatic Disease Management:
- Hormone-sensitive: ADT + docetaxel or novel agents
- Castration-resistant: Sequential use of approved therapies
- Bone metastases: Zoledronic acid/denosumab for SRE prevention
Treatment-Related Complications:
Surgical Complications (Radical Prostatectomy):
- Urinary incontinence: 5-20% persistent at 1 year
- Erectile dysfunction: 50-80% immediate, improves with time/PDE5 inhibitors
- Bladder neck contracture: 5-15%
- Lymphocele: 1-5%
- Anastomotic stricture: 2-10%
Radiation Therapy Complications:
- Acute: Proctitis, cystitis, fatigue, skin reactions
- Late: Rectal bleeding, urethral stricture, bladder fibrosis
- Sexual dysfunction: 30-50% erectile dysfunction
- Secondary malignancies: Rare (less than 1%)
Hormonal Therapy Complications:
- Hot flashes: 50-80%
- Sexual dysfunction: 90% libido loss, 70% erectile dysfunction
- Osteoporosis: 20-50% bone loss, increased fracture risk
- Metabolic syndrome: Weight gain, insulin resistance, dyslipidemia
- Cardiovascular events: Increased risk with GnRH agonists
- Cognitive changes: Memory impairment, depression
- Gynecomastia: 40-70% with anti-androgens
Disease-Related Complications:
- Bladder outlet obstruction: Retention, hydronephrosis
- Ureteric obstruction: Renal failure
- Spinal cord compression: Neurological deficits
- Pathologic fractures: Pain, immobility
- Hypercalcemia: From bone metastases
- Malignant pleural effusion/pericardial effusion
Chemotherapy Complications:
- Neutropenia, anemia, thrombocytopenia
- Peripheral neuropathy (docetaxel, cabazitaxel)
- Fatigue, nausea, alopecia
- Cardiotoxicity (rare)
Prognosis varies significantly by stage at diagnosis and response to therapy. Modern risk stratification and treatment intensification have improved outcomes substantially.
5-Year Survival Rates:
- Localized disease: 98-100%
- Regional disease: 95-100%
- Distant metastases: 30-35%
- Overall 5-year relative survival: 97%
Prognostic Factors:
- Gleason score/Grade Group
- PSA level at diagnosis
- Clinical stage
- Volume of disease
- Response to initial therapy
- Comorbidities and performance status
Biochemical Recurrence Risk:
- Low risk: 10-20% at 10 years
- Intermediate risk: 20-40% at 10 years
- High risk: 40-60% at 10 years
Metastatic Disease Prognosis:
- Hormone-sensitive: Median OS 4-6 years with modern therapies
- Castration-resistant: Median OS 2-3 years, varies by prior treatments
- Poor prognostic factors: Visceral metastases, short PSA doubling time, high ALP
Quality of Life Considerations:
- Treatment impacts urinary, sexual, and bowel function
- Long-term hormonal therapy affects bone health and cardiovascular risk
- Psychological impact: Anxiety, depression, body image issues
- Supportive care improves outcomes and quality of life
Major Guidelines
- NCCN (2023): Categorizes disease by risk groups (Very Low to Very High) for tailored therapy. Recommends genetic testing for High/Very High risk.
- EAU (2023): Strong recommendation for mpMRI before biopsy.
- AUA/ASTRO (2022): Emphasizes Shared Decision Making and active surveillance for Low Risk disease.
Landmark Clinical Trials
1. STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer)
- Design: Multi-arm, multi-stage platform trial.
- Key Finding: Adding Abiraterone or Docetaxel to standard ADT in high-risk locally advanced or metastatic disease significantly improves Overall Survival.
- Impact: Established early intensification (doublet/triplet therapy) as standard of care for hormone-sensitive disease.
2. CHAARTED (Chemohormonal Therapy vs ADT)
- Question: Does early chemo help in hormone-sensitive metastatic disease?
- Result: Docetaxel + ADT improved median OS by 13.6 months (57.6 vs 44.0) compared to ADT alone.
- Nuance: Benefit was primarily driven by "High Volume" disease (visceral mets or >4 bone lesions).
3. PROTECT (Prostate Testing for Cancer and Treatment)
- Question: Surgery vs Radiation vs Monitoring for localized disease.
- Result: At 10 years, NO difference in specific mortality between the three groups (approx 1%).
- Trade-off: Surgery/RT reduced metastasis progression but increased side effects (incontinence/ED). Monitoring had fewer side effects but higher metastasis risk.
4. PROfound (Olaparib in mCRPC)
- Mechanism: PARP Inhibitor in patients with Homologous Recombination Repair (HRR) gene mutations (e.g., BRCA2).
- Result: Improved Radiographic Progression-Free Survival (rPFS) and Overall Survival in patients with BRCA1/2 or ATM mutations.
- Impact: First targeted therapy for genetically defined prostate cancer.
5. VISION (Lu-PSMA-617)
- Modality: Theranostics (Radioligand Therapy).
- Result: Lutetium-177-PSMA-617 added to standard care improved OS (15.3 vs 11.3 months) in pre-treated mCRPC.
- Requirement: Must have PSMA-positive PET scan.
"What is Prostate Cancer?" Prostate cancer develops when cells in the prostate gland begin to grow uncontrollably. The prostate is a walnut-sized gland that produces fluid for semen. Most prostate cancers grow slowly and may never cause problems, but some can spread beyond the prostate to other parts of the body.
"How Did I Get This?" The exact cause is unknown, but risk increases with age, family history, and certain genetic factors. Lifestyle factors like diet and exercise also play a role. It's not caused by sexual activity or masturbation.
"What Tests Will I Need?" You'll need blood tests (PSA), possibly a prostate biopsy, and imaging studies like MRI or CT scans. These help determine the cancer's stage and aggressiveness.
"What Are My Treatment Options?" Treatment depends on cancer stage, your age, overall health, and preferences:
- Active surveillance: Regular monitoring for low-risk cancers
- Surgery: Removing the prostate (prostatectomy)
- Radiation: Using high-energy rays to kill cancer cells
- Hormone therapy: Blocking male hormones that fuel cancer growth
- Chemotherapy: Drugs to kill cancer cells
- Immunotherapy: Boosting your immune system to fight cancer
"What Are the Side Effects?" Treatments can affect urination, sexual function, and bowel habits:
- Surgery may cause urinary incontinence or erectile dysfunction
- Radiation can cause bowel or urinary problems
- Hormone therapy often causes hot flashes, fatigue, and sexual changes
- Chemotherapy may cause nausea, hair loss, and increased infection risk
"What Is My Prognosis?" Most men with prostate cancer do well, especially when caught early. 5-year survival rates are over 98% for localized disease and 97% overall. Your doctor will give you a personalized prognosis based on your specific situation.
"What About My Sex Life?" Sexual function can be affected by treatments, but many men recover function over time. There are treatments like medications, injections, or devices that can help. Discuss your concerns openly with your doctor.
"Will I Need Follow-Up?" Yes, regular PSA tests, doctor visits, and possibly imaging studies to monitor for recurrence. Early detection of any problems allows for prompt treatment.
"Can I Prevent Recurrence?" Healthy lifestyle choices help: regular exercise, balanced diet, maintaining healthy weight, and not smoking. Follow your doctor's recommendations for follow-up care.
-
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. PMID: 33538338
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Rawla P. Epidemiology of Prostate Cancer. World J Oncol. 2019;10(2):63-89. PMID: 31068988
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Pernar CH, Ebot EM, Wilson KM, Mucci LA. The Epidemiology of Prostate Cancer. Cold Spring Harb Perspect Med. 2018;8(12):a030361. PMID: 30054404
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Attard G, Murphy L, Clarke NW, et al. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022;399(10323):447-460. PMID: 34953525
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Fizazi K, Gillessen S, ESMO Guidelines Committee. Updated treatment recommendations for prostate cancer from the ESMO Clinical Practice Guideline considering treatment intensification and use of novel systemic agents. Ann Oncol. 2023;34(6):557-563. PMID: 36958590
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Henry A, Pieters BR, André Siebert F, Hoskin P; UROGEC group of GEC ESTRO with endorsement by the European Association of Urology. GEC-ESTRO ACROP prostate brachytherapy guidelines. Radiother Oncol. 2022;167:244-251. PMID: 34999134
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Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746. PMID: 26244877
-
Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360. PMID: 28728019
-
Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. 2019;381(2):121-131. PMID: 31157963
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Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019;381(1):13-24. PMID: 31157964
-
Smith MR, Saad F, Chowdhury S, et al. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol. 2021;79(1):150-158. PMID: 33172728
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Mottet N, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2021;79(2):243-262. PMID: 33172728
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Cornford P, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. Eur Urol. 2021;79(2):263-282. PMID: 33172729
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Sathianathen NJ, Konety BR, Crook J, Saad F, Lawrentschuk N. Landmarks in prostate cancer. Nat Rev Urol. 2018;15(10):627-642. PMID: 30065357
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Nguyen PL, Alibhai SM, Basaria S, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015;67(5):825-836. PMID: 25097095
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Fenton JJ, Weyrich MS, Durbin S, et al. Prostate-Specific Antigen-Based Screening for Prostate Cancer: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018;319(18):1914-1931. PMID: 29801018
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George DJ, Sartor O, Miller K, et al. Treatment Patterns and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer in a Real-world Clinical Practice Setting in the United States. Clin Genitourin Cancer. 2020;18(3):e227-e237. PMID: 32057714
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Francini E, Agarwal N, Castro E, et al. Intensification Approaches and Treatment Sequencing in Metastatic Castration-resistant Prostate Cancer: A Systematic Review. Eur Urol. 2024;S0302-2838(24)02657-3. PMID: 39306478
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Scher HI, Morris MJ, Stadler WM, et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34(12):1402-1418. PMID: 26903579
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Pommier P, Ferré M, Blanchard P, et al. Prostate cancer brachytherapy: SFRO guidelines 2021. Cancer Radiother. 2022;26(1-2):190-199. PMID: 34955422
Key Examination Findings:
- Digital rectal examination: Palpable nodule, asymmetry, induration
- Lymph node assessment: Supraclavicular and inguinal adenopathy
- Spinal tenderness: Suggests metastatic disease
- Lower extremity edema: May indicate lymphatic or venous obstruction
Clinical Scenarios:
- Elderly male with LUTS: Consider PSA testing and DRE
- Bone pain in known prostate cancer: Evaluate for metastases
- Incidental PSA elevation: Correlate with DRE findings and risk factors
- Abnormal DRE in asymptomatic patient: Proceed to biopsy
Red Flag Recognition:
- Spinal cord compression: Emergency - requires immediate imaging and intervention
- Acute urinary retention: May need urgent catheterization
- Pathologic fractures: Suggest aggressive metastatic disease
-
STAMPEDE Trial (2018: Abiraterone + ADT improves survival in high-risk non-metastatic disease PMID: 34953525 - HR for metastasis-free survival: 0.53 (95% CI 0.44-0.64 - 6-year metastasis-free survival: 82% vs 69%
-
CHAARTED Trial (2015: Docetaxel + ADT improves OS in metastatic hormone-sensitive disease PMID: 25830416 - Median OS: 57.6 vs 44.0 months (HR 0.61 - Benefit greatest in high-volume disease
-
LATITUDE Trial (2017: Abiraterone + ADT improves OS in high-risk metastatic disease PMID: 28728019 - 3-year OS: 66% vs 49% (HR 0.62 - Significant PFS improvement
-
ENZAMET Trial (2021: Enzalutamide + ADT improves OS vs standard ADT PMID: 34534429 - 3-year OS: 80% vs 72% (HR 0.67 - Consistent benefit across subgroups
-
TITAN Trial (2020: Apalutamide + ADT improves OS in metastatic disease PMID: 32469185 - Median PFS: 22.1 vs 14.7 months
- OS benefit maintained at final analysis
Meta-Analyses:
- Novel AR-targeted agents in mCRPC: Consistent OS benefit (4-6 months PMID: 39306478- Treatment intensification in localized disease: Improved outcomes with multimodal therapy PMID: 32057714 Systematic Reviews:
- Active surveillance outcomes: Excellent long-term cancer control in low-risk disease PMID: 29801018- Adverse effects of ADT: Comprehensive assessment of toxicity profile PMID: 25097095
"What is Prostate Cancer?" Prostate cancer develops when cells in the prostate gland begin to grow uncontrollably. The prostate is a walnut-sized gland that produces fluid for semen. Most prostate cancers grow slowly and may never cause problems, but some can spread beyond the prostate to other parts of the body.
"How Did I Get This?" The exact cause is unknown, but risk increases with age, family history, and certain genetic factors. Lifestyle factors like diet and exercise also play a role. It's not caused by sexual activity or masturbation.
"What Tests Will I Need?" You'll need blood tests (PSA, possibly a prostate biopsy, and imaging studies like MRI or CT scans. These help determine the cancer's stage and aggressiveness.
"What Are My Treatment Options?" Treatment depends on cancer stage, your age, overall health, and preferences:
- Active surveillance: Regular monitoring for low-risk cancers
- Surgery: Removing the prostate (prostatectomy- Radiation: Using high-energy rays to kill cancer cells
- Hormone therapy: Blocking male hormones that fuel cancer growth
- Chemotherapy: Drugs to kill cancer cells
- Immunotherapy: Boosting your immune system to fight cancer
"What Are the Side Effects?" Treatments can affect urination, sexual function, and bowel habits:
- Surgery may cause urinary incontinence or erectile dysfunction
- Radiation can cause bowel or urinary problems
- Hormone therapy often causes hot flashes, fatigue, and sexual changes
- Chemotherapy may cause nausea, hair loss, and increased infection risk
"What Is My Prognosis?" Most men with prostate cancer do well, especially when caught early. 5-year survival rates are over 98% for localized disease and 97% overall. Your doctor will give you a personalized prognosis based on your specific situation.
"What About My Sex Life?" Sexual function can be affected by treatments, but many men recover function over time. There are treatments like medications, injections, or devices that can help. Discuss your concerns openly with your doctor.
"Will I Need Follow-Up?" Yes, regular PSA tests, doctor visits, and possibly imaging studies to monitor for recurrence. Early detection of any problems allows for prompt treatment.
"Can I Prevent Recurrence?" Healthy lifestyle choices help: regular exercise, balanced diet, maintaining healthy weight, and not smoking. Follow your doctor's recommendations for follow-up care.
- Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020. CA Cancer J Clin. 2021.
- Mottet N et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. Eur Urol. 2021.
- Sweeney CJ et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer (CHAARTED). N Engl J Med. 2015.
- James ND et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy (STAMPEDE). N Engl J Med. 2017.
- Hamdy FC et al. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer (PROTECT). N Engl J Med. 2016.
- de Bono J et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer (PROfound). N Engl J Med. 2020.
- Sartor O et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer (VISION). N Engl J Med. 2021.
- Parker C et al. Prostate cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2020.
Key Examination Findings:
- Digital rectal examination: Palpable nodule, asymmetry, induration
- Lymph node assessment: Supraclavicular and inguinal adenopathy
- Spinal tenderness: Suggests metastatic disease
- Lower extremity edema: May indicate lymphatic or venous obstruction
Clinical Scenarios:
- Elderly male with LUTS: Consider PSA testing and DRE
- Bone pain in known prostate cancer: Evaluate for metastases
- Incidental PSA elevation: Correlate with DRE findings and risk factors
- Abnormal DRE in asymptomatic patient: Proceed to biopsy
Red Flag Recognition:
- Spinal cord compression: Emergency - requires immediate imaging and intervention
- Acute urinary retention: May need urgent catheterization
- Pathologic fractures: Suggest aggressive metastatic disease
- Severe hypercalcemia: Paraneoplastic manifestation requiring urgent treatment