Diagnosis
Key Examinations for the Diagnosis of Prostate Cancer
- Prostate-specific antigen (PSA) level
- Digital rectal examination (DRE)
- Prostate biopsy
Staging
- Determines the extent of cancer upon diagnosis
- Important factor in the choice of treatment and provides information about the prognosis of the disease
Tumor, Nodes and Metastasis (TNM) System
- Developed by the American Joint Committee on Cancer (AJCC) and Union Internationale Contre le Cancer
Clinical T (cT) | ||
T - Primary Tumor | ||
TX | Primary tumor cannot be assessed | |
T0 | No evidence of primary tumor | |
T1 | Clinically inapparent tumor not palpable or visible by imaging | |
T1a | Tumor incidental histological finding in 5% or less of tissue resected | |
T1b | Tumor incidental histological finding in more than 5% of tissue resected | |
T1c | Tumor identified by needle biopsy (secondary to elevated PSA level) | |
T2 | Tumor confined within the prostate gland (by needle biopsy) | |
T2a | Tumor involves 1/2 of one lobe or less | |
T2b | Tumor involves >1/2 of one lobe but not both lobes | |
T2c | Tumor involves both lobes | |
T3 | Tumor extends through the prostatic capsule | |
T3a | Extracapsular extension (unilateral or bilateral) | |
T3b | Tumor invades the seminal vesicle(s) | |
T4 | Tumor fixed or invades adjacent structures other than the seminal vesicles (bladder, rectum, levator muscles, and/or pelvic wall) | |
Pathological T (pT) | ||
T - Primary Tumor | ||
T2 | Confined in the organ | |
T3 | Positive extension extraprostatically | |
T3a | Unilateral or bilateral extraprostatic extension | |
T3b | Tumor invades seminal vesicle(s) | |
T4 | Fixed tumor or invades adjacent structures other than the seminal vesicles (ie external sphincter, rectum, bladder, levator muscles, &/or pelvic wall) | |
N - Regional Lymph Nodes | ||
NX | Regional lymph nodes cannot be assessed | |
N0 | No regional lymph node metastasis | |
N1 | Regional lymph node metastasis present | |
M - Distant metastasis1 | ||
M0 | No distant metastasis | |
M1 | Distant metastasis | |
M1a | Non-regional lymph node(s) | |
M1b | Bone(s) | |
M1c | Other site(s) with or without bone disease | |
1The most advanced category (M1c) should be used when >1 metastasis site is present
Adapted from: National Comprehensive Cancer Network. NCCN guidelines: prostate cancer. Version 3.2018. |
Staging
- Should be based on the prostate-specific antigen (PSA) level, tumor grade, and positive prostate biopsies
Stage | Tumor | Node | Metastasis | PSA | Grade Group |
I | cT1a-c | N0 | M0 | PSA <10 | 1 |
cT2a | N0 | MO | PSA <10 | 1 | |
pT2 | NO | MO | PSA <10 | 1 | |
IIA | cT1a-c | N0 | M0 | PSA ≥10<20 | 1 |
cT2a | N0 | MO | PSA ≥10<20 | 1 | |
pT2 | NO | MO | PSA ≥10<20 | 1 | |
cT2b | NO | MO | PSA <20 | 1 | |
cT2c | NO | MO | PSA <20 | 1 | |
IIB | T1-2 | N0 | M0 | PSA <20 | 2 |
IIC | T1-2 | N0 | MO | PSA <20 | 3 |
T1-2 | NO | MO | PSA <20 | 4 | |
IIIA | T1-2 | NO | MO | PSA ≥20 | 1-4 |
IIIB | T3-T4 | N0 | M0 | Any PSA | 1-4 |
IIIC | Any T | N0 | MO | Any PSA | 5 |
IVA | Any T | N1 | M0 | Any PSA | Any |
IVB | Any T | Any N | M1 | Any PSA | Any |
Adapted from: National Comprehensive Cancer Network. NCCN guidelines: prostate cancer. Version 3.2018. NCCN website. 2018.; American Cancer Society. Prostate cancer staging. 2018. |
Risk Stratification
- Based on the prostate-specific antigen (PSA) level, biopsy, Gleason score, and tumor, nodes and metastasis (TNM) classification
- Helps in decision making for the management of patients diagnosed with prostate cancer
Risk Group | Clinical Stage | PSA | Grade Group or Gleason Score | Others | |||
Clinically Localized | |||||||
---|---|---|---|---|---|---|---|
Very Low | T1c | & | <10 ng/mL | & | Grade group 1/Gleason score ≤6 | & | <3 prostate biopsy fragments/cores positive, with ≤50% cancer in each fragment/core & PSA density <0.15 ng/mL/g |
Low | T1-T2a | & | <10 ng/mL | & | Grade group 1/Gleason score ≤6 | ||
Intermediate | T2b-T2c | or | 10-<20 ng/mL | or | Grade group 2-3 | ||
Favorable | T2b-T2c | or | 10-20 ng/mL | or | Grade group 2/Gleason score 3+4=7 | & | percentage of positive biopsy core <50% |
Unfavorable | T2b-T2c | or | 10-20 ng/mL | or | Grade group 2/Gleason score 3+4=7 or Grade group 3/Gleason score 4+3=7 | ||
High | T3a | or | >20 ng/mL | or | Grade group 4/Gleason score 8 or Grade group 5/Gleason score 4+5=9 | ||
Locally Advanced | |||||||
Very High | T3b-T4 | Primary Grade group 5 or Grade group 4 or 5/Gleason score 8-10 in >4 cores | |||||
Regional | Any T, N1, M0 | ||||||
Metastatic | Any T, any N, M1 | ||||||
National Comprehensive Cancer Network. NCCN guidelines: prostate cancer version 3.2018. NCCN website. 2018. pp PROS-2 Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO). Clinically localized prostate cancer guideline: Risk stratification, shared decision making, and care options: 2017 update. 2017. pp 683-685; European Association of Urology. Guidelines on prostate cancer. 2014. pp12-13 |
Cancer of the Prostate Risk Assessment (CAPRA)
- A straightforward scoring system (0-10) that predicts likelihood of metastasis, cancer-specific mortality, and overall survival
- Based on the patient’s age, prostate-specific antigen (PSA) levels, Gleason score, clinical stage, and percent of malignant biopsy cores
- Also predicts disease recurrence after radical prostatectomy
Assessment
Gleason Score
- Useful in determining tumor grade, prognostic risk, and management strategies
Gleason Score | Definition |
Gleason X | Gleason score cannot be assessed |
Gleason <6 | Well differentiated (slight anaplasia) |
Gleason 7 | Moderately differentiated (moderate anaplasia) |
Gleason 8-10 | Poorly differentiated/undifferentiated (marked anaplasia) |
Physical Examination
Digital Rectal Examination (DRE)
- Detects prostatic enlargement with volume of >0.2 mL
- Abnormal DREs are associated with high Gleason scores and may be considered for prostate biopsy
Laboratory Tests
Prostate-Specific Antigen (PSA) Level
- A kallikrein-like serine protease produced by prostatic epithelial cells
- Risk for prostate cancer increases with increasing level of prostate-specific antigen (PSA) and may warrant a prostate biopsy
- Predicts extension outside the prostate gland, seminal vesicle invasion, and lymphadenopathies
- Baseline results should be obtained prior to starting treatment as it is also a good measurement for therapeutic efficacy
Prostate Biopsy
- Most common method used in diagnosing prostatic carcinoma
- Should only be offered if prostate-specific antigen (PSA) levels and digital rectal examination (DRE) highly suggest prostate cancer
- Transrectal ultrasound (TRUS)-guided core-needle prostate biopsy is highly recommended for men with prostate-specific antigen (PSA) levels of >4 ng/mL
- Indications:
- Increased risk for prostate cancer and with prostate-specific antigen (PSA) levels of 2.5-4 ng/mL
- Increased prostate-specific antigen (PSA) levels of >0.35 ng/mL within 1 year from baseline of <4 ng/mL
- Increased prostate-specific antigen (PSA) levels of >0.75 ng/mL within 1 year from baseline of 4-10 ng/mL
- Prostate-specific antigen (PSA) levels too high for age range
- Obtaining a minimum of 10-12 cores are recommended
- Should be done under antibiotic coverage
- The perineal approach (transperineal 3D prostate mapping biopsy) is a useful option for special circumstances (eg rectal amputation)
Other Tests
Other Tumor Markers
- Have been associated with prostate cancer diagnosis but are not routinely performed
- Include apoptosis markers [eg B-cell lymphoma 2 (Bcl-2), BCL2 Associated X Protein (Bax)], proliferation rate markers (eg Ki67), p53 mutation/expression, p27, E-cadherin, deoxyribonucleic acid (DNA) plody, p16
- ProPSA (part of the Prostate Health Index) & prostate specific antigen 3 (PCA3) are newly developed, US FDA-approved biomarkers to detect prostate cancer
- An increase in serum acid phosphatase levels may indicate poor prognosis in patients with localized and disseminated disease
Imaging
- Should be based on prostate-specific antigen (PSA) results, Gleason score, and patient’s health status
Plain Film Radiography
- May be used to assess for presence of bone pathologies in symptomatic patients
Ultrasonography
- Transrectal ultrasound (TRUS) may be used to assess the prostate gland if prostate-specific antigen (PSA) levels and digital rectal examination (DRE) results are inconclusive
- Also used as a guide during transrectal prostate biopsies
Computed Tomography (CT) Scan
- May be used to assess for presence of bone pathologies
- May be used for lymph node staging in asymptomatic patients at intermediate-high risk [prostate-specific antigen (PSA) level >10 ng/ mL, Gleason score >8, or clinical stage >T3]
Magnetic Resonance Imaging (MRI)
- Multiparametric MRI (mpMRI) by diffusion-weighted imaging or hydrogen 1 (H1)-spectroscopy may be done to assess if repeat prostate biopsy is needed in patients with negative results in transrectal ultrasound (TRUS)
- Detects large and poorly differentiated tumors and extracapsular extension
- Sensitivity at >2 cc: 67-75% for Gleason <6; 97% for Gleason 7; 100% for Gleason >8
- Positive results may suggest repeat prostate biopsy
Radionuclide Bone Scan
- Used to assess for possible bone involvement
- May be performed for symptomatic patients with prostate-specific antigen (PSA) results of >10 ng/mL, Gleason score >8 and those with decreasing prostate-specific antigen (PSA) doubling time
Gallium 68-Prostate Specific Membrane Antigen (PSMA) PET/CT Scan
- A new PET tracer which demonstrates high sensitivity with histopathological diagnosis
- Can be utilized in staging prostate cancer
Screening
Recommended for men:
- 50 years of age at average risk for prostate cancer and with life expectancy of >10 years
- 45 years of age at high risk for developing prostate cancer (eg African American descent, with 1st-degree relatives diagnosed with prostate cancer who are <65 years old)
- 40 years of age with 1st-degree relatives diagnosed with prostate cancer who are <65 years old and with previous prostate-specific antigen (PSA level of >1 ng/mL)
- With previous prostate-specific antigen (PSA) level of >2 ng/mL taken at 60 years old
- With initial screening which includes prostate-specific antigen (PSA) and digital rectal examination (DRE)
- With negative results but at risk for prostate cancer, repeat screening should be done depending on the prostate-specific antigen (PSA) result:
- Prostate-specific antigen (PSA) <2.5 ng/mL = every 2 years
- Prostate-specific antigen (PSA) >2.5 ng/mL = yearly