Nicholas J. Kuntz, MD
Judd W. Moul, MD, FACS
BASICS
DESCRIPTION
• Biopsy-proven adenocarcinoma of the prostate, clinically confined to the prostate gland
• Clinical T1 or T2, N0, M0
EPIDEMIOLOGY
Incidence
• Prostate cancer (CaP) (American Cancer Society Data)
– Estimated 233,000 new cases and 29,480 deaths in 2014 in US
• Localized prostate cancer (LCaP)
– 81% of newly diagnosed CaP
Prevalence
• Age dependent
– CaP cumulative prevalence in US men
Age 50–60: 44%; Age 70–80: 83%
• 20–35% worldwide
RISK FACTORS
• Age
• Family history of CaP with highest risk in 1st-degree relative
– Suggestion that familial breast cancer increasies prostate cancer risk
• African American race
– 40% increased risk of disease
– 2.4 times risk of mortality
Genetics
See “Prostate cancer, general considerations”
PATHOPHYSIOLOGY
• Genetic predisposition
• Chronic inflammatory states
• Oxidative stress
ASSOCIATED CONDITIONS
• Benign prostatic hypertrophy (BPH)
• Lower urinary tract symptoms (LUTS) (unrelated to cancer)
• Obesity
GENERAL PREVENTION
• See also “Prostate Cancer, prevention”
• There are unfortunately no approved agents for the chemoprevention of CaP. Major clinical trials include:
• 5α-reductase inhibitors
– Finasteride (PCPT trial, 2003)
25% CaP risk reduction
– Dutasteride (REDUCE trial, 2009)
27% CaP risk reduction
• Vitamin E and selenium (SELECT trial, 2011)
– Increases the risk of CaP by 17%
DIAGNOSIS
HISTORY
• LCaP is rarely symptomatic
• Unintentional weight loss or new-onset skelet al pain suggests nonlocalized disease
• LUTS
– More commonly attributed to BPH
PHYSICAL EXAM
• Digital rectal exam (DRE)
– No palpable nodule (cT1)
– Nodule confined to prostate gland (cT2)
– Ablation of lateral sulcus or palpable seminal vesicles suggests more advanced disease than T2
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Prostate-specific antigen (PSA)
– Produced by prostatic epithelium
– Half-life of 2–3 days; Not specific to CaP
– A continuous parameter
The higher the value, the more likely the existence of CaP (1)[A]
• Routine PSA screening is controversial
– 2013 AUA Guidelines (2):
Under age 40 yr: Do not screen [C]
40–54 yr, average risk: Do not screen [C]
<55 yr at higher risk: Individualized decision [C]
55–69 yr: Shared decision-making if considering PSA screening [B]
Greatest benefit of screening in men ages 55–69 yr
Routine screening interval: 2 yr [C]
>70 yr and <10–15-yr life expectancy: Do not screen [C]
• Other PSA parameters
– PSA velocity/doubling time
Limited use in diagnosis (1)[A]
Velocity >2 ng/mL: Increased risk for death from CaP
– % free PSA <10
Increased (56%) risk of cancer (1)[A]
– PSA density
≥0.15 mg/mL/g suggests CaP
• CaP antigen 3 (PCA3) (see “PCA3 Prostate Cancer Gene 3 urine assay”)
– Limited clinical use in diagnosis
– May help in decision to a repeat biopsy in men with a negative 1st biopsy (1)[A]
Imaging
• 2014 NCCN Guidelines for LCaP:
– No imaging if low risk
– Bone scan: PSA >10 ng/mL or Gleason ≥8
– Pelvic CT or MRI
Lymph node involvement risk >10%
• ProstaScint imaging: Not indicated for LCaP
• No imaging modality can accurately estimate the extent of tumor and location within or surrounding the prostate
Diagnostic Procedures/Surgery
• Prostate biopsy (3)[C]
– Diagnosis is based on histologic exam
– Transrectal ultrasound guided (TRUS) transrectal or transperineal needle biopsy
Laterally directed, 18G, 10–12 cores
Increases detection rate
– Periprostatic local anesthetic injection
– Antibiotic prophylaxis is always recommended
– Infection rate: 0.5–1% (see “Prostate biopsy, Infections and Complications”)
Pathologic Findings
• Gleason score (See “Gleason Grading/Scoring System”)
• Proportion of biopsies positive for carcinoma
• Presence of extraprostatic extension
• High-grade PIN and perineural invasion is usually reported
DIFFERENTIAL DIAGNOSIS
• Abnormal DRE: Granulomatous prostatitis prostatic cyst, calcifications, cancer
• Elevated PSA: UTI, BPH, acute or chronic prostatitis, recent prostatic instrumentation
TREATMENT
GENERAL MEASURES
• Assess life expectancy, overall health status, and tumor characteristics prior to treatment decisions (4)[A]
• Review risk and benefits of all treatments and engage patient in informed decision making process.
• Treatment recommendations based on cancer biology, patient overall health, life expectancy, and preferences
• Gleason score and tumor stage are predictive of cancer outcomes
• Risk strata are used to develop treatment recommendations (4)[A]
– Low risk: PSA 10 and a Gleason score of 6 or less and clinical stage T1c or T2a
– Intermediate risk: PSA >10–20 or a Gleason score of 7 or clinical stage T2b
– High risk: PSA >20 or a Gleason score of 8 to 10 or clinical stage T2c
MEDICATION
First Line
• Primary androgen deprivation therapy (ADT)
– Rarely indicated for LCaP (4)[C]
Palliation of symptomatic patients
Extensive or poorly differentiated tumors
Short life expectancy
– Not recommended by 2014 NCCN Guidelines
• Neoadjuvant ADT for surgical treatment
– Not recommended (1)[A]
• Neoadjuvant/concurrent androgen deprivation for 6 mo–3 yr with XRT increases survival vs. XRT alone or hormonal therapy alone (select intermediate and all high-risk patients)
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Radical prostatectomy (RP)
– Removal of prostate gland, seminal vesicles, and ampulla of the vas; pelvic lymph node dissection for elevated risk of positive nodes
– Cancer “cure” in truly localized disease
– Option for low, intermediate risk with ≥10-yr life expectancy and selected high-risk patients (1)[B]
– Similar survival between RP and watchful waiting in low-risk CaP, <65 yr (4)[B]
– Technique:
Open (perineal or retropubic)
Laparoscopic (LRP), Robotic assisted laparoscopic prostatectomy (RALP): Lower blood loss and transfusion rates; oncologic and long-term outcome similar
Pelvic lymphadenotomy (PLND) if predicted nodal mets is ≥2%
Nerve-sparing surgery: Preoperatively potent patients, T1c, Gleason <7, and PSA <10 (1)[B]
Non–nerve-sparing for high risk (high erectile dysfunction rates)
• Salvage RP
– Highly selected patients with local recurrence
– Absence of metastatic disease
– High morbidity
ADDITIONAL TREATMENT
Radiation Therapy
• External beam RT (EBRT)
– Intensity-modulated RT (IMRT) is preferred
– Image-guided RT (IGRT) if dose >78 Gy
– Dose: Low risk: 75–79 Gy, 8–9-wk fractionation; intermediate/high risk: Up to 81 Gy
– Combined with ADT
Neoadjuvant, concomitant, or adjuvant ADT
Increased survival in high-risk patients if given before and during EBRT (1)[B]
4–6 mo or 2–3 yr for high risk (high Gleason or high volume based on biopsy)
– Irradiation to the pelvic lymph nodes; no general indication; ongoing trials (1)[B]
• Brachytherapy
– Delivered via interstitial seeds
Temporary: High-dose rate (HDR): Ir192
Permanent: Low-dose rate (LDR): I125 or Pd103
– Monotherapy: Low-risk disease
Dose: I125 145 Gy and Pd103 125 Gy
– Combined with EBRT: Intermediate/high risk
40–50 Gy of EBRT
± 4–6 mo of ADT
– Higher risk of side effects:
Previous TURP
Large (60–80 g) or small (<20 g) gland
Bladder outlet obstruction
• Stereotactic body RT (SBRT), ie, CyberKnife
– Highly conformal, high dose
– Hypofractionation (as little as 5 fractions)
– May be equivalent to EBRT; under trial
• Proton therapy
– Not recommended for routine use currently
Additional Therapies
• Active Surveillance
– See “Prostate Cancer, Very Low Risk and Active Surveillance”
• Cryosurgical ablation of the prostate (CSAP)
– Patients not suitable for RP or life expectancy <10 yr, gland <40 mL
– Freezing techniques to induce cell death
Placement of 12–15 17G cryoneedles under TRUS guidance
Thermosensors at external sphincter and bladder neck
Insertion of urethral warmer
2 freeze–thaw cycles: –40°C at midgland and at the neurovascular bundle
– NCCN: Currently not recommended as routine primary therapy for LCaP
• High-intensity focused ultrasound (HIFU) and vascular-targeted photodynamic (VTP) therapies
– Currently not considered valid treatment options
Complementary & Alternative Therapies
Not applicable
ONGOING CARE
PROGNOSIS
• Dependent on risk strata
– Low, intermediate, and high risk
– Indicate probability of biochemical failure after definitive local therapy
• See on line prediction tools such as http://www.mskcc.org/cancer-care/adult/prostate/prediction-tools orPartin tables: http://urology.jhu.edu/prostate/partintables.php (Accessed August 23, 2014)
COMPLICATIONS
• RP
– Significantly reduced if performed in a high-volume hospital and experienced surgeon
– Intraoperative: Rectal injury (0–5%), major bleeding (1–12%), death (0–2%)
– Postoperative: Deep vein thrombosis (0–8%), pulmonary embolus (1–8%), lymphocele (1–3%)
– Long term: Incontinence (0–50%), stricture (2–9%), impotence (30–100%)
• RT
– Short term: Bowel symptoms (bleeding, diarrhea, fecal incontinence), irritative voiding symptoms
– Long term:
Genitourinary (16%): Strictures, hematuria, cystitis, incontinence
Gastrointestinal (10%) Proctitis, chronic diarrhea, small bowel obstruction
Increased risk of secondary cancers
FOLLOW-UP
Patient Monitoring
• No consensus for follow-up after definitive treatment of LCaP
• Usually followed for at least 10 yr
• NCCN: PSA every 6–12 for 5 yr, then every year, DRE every year (omitted if PSA undetectable)
• Palpable nodule on DRE and rising PSA can indicate local disease recurrence (1)[B]
• See “Prostate cancer, biochemical recurrence (elevated PSA)”
Patient Resources
• National Cancer Institute. www.cancer.gov/cancertopics/types/prostate
• AUA patient guide. www.auanet.org/common/pdf/education/clinical-guidance/Prostate-Cancer-PatientGuide.pdf
REFERENCES
1. Heidenreich A, Bellmunt J, Bolla M, et al. EAU guidelines on prostate cancer. Part 1: Screening, diagnosis, and treatment of clinically localised disease. Euro Urol. 2011;59(1):61–71.
2. Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA guideline. J Urol. 2013;190(2):419–426.
3. Damber JE, Aus G. Prostate cancer. Lancet. 2008;17:371(9625):1710–1721.
4. Thompson I, Thrasher JB, Aus G, et al. Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol. 2007;177(6):2106–2131.
ADDITIONAL READING
• Healy KA, Gomella LG. Retropubic, laparoscopic, or robotic radical prostatectomy: Is there any real difference? Semin Oncol. 2013;40(3):286–296.
• NCCN Practice Guidelines Version 1.2014. http://www.nccn.org./ Accessed January 6, 2014
• Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367(3):203–213.
See Also (Topic, Algorithm, Media)
• Prostate Cancer, Castration resistant
• Prostate Cancer, Genomic markers
• Prostate Cancer, Locally Advanced (T3, T4)
• Prostate Cancer, Metastatic (N+, M+)
• Prostate cancer, Very Low Risk and Active Surveillance
• PSA Elevation, General
• Reference Tables: TNM: Prostate Cancer
CODES
ICD9
• 185 Malignant neoplasm of prostate
• V16.42 Family history of malignant neoplasm of prostate
ICD10
• C61 Malignant neoplasm of prostate
• Z80.42 Family history of malignant neoplasm of prostate
CLINICAL/SURGICAL PEARLS
• Represents majority of newly diagnosed men with CaP; minority of men will die from their disease.
• Nerve-sparing RP technique is standard of care.
• Surgical outcomes are highly dependent on surgeon experience.
• Radiation techniques, improving disease control, and reducing side effects.
• Consider active surveillance if low risk and <10-yr life expectancy.