Prostate Cancer by Dr. Jeffrey Wong

Prostate Cancer

Epidemiology

Incidence rates highest among African Americans, intermediate in whites and lowest in Japanese and Chinese
Also high among Switzerland, Norway, Luxembourg, Iceland and Canada

Definitive Risk Factors

Age: prevalence of prostate cancer increases with age, and after age 50, both incidence and mortality rates increase at near exponential rates
Family History: risk of man developing Pca depends on age of onset of and number of affected relatives
Race: black men in US have higher incidence rate of clinical prostate cancer than white men, black men are routinely diagnosed with later stage disease, and survival rates, even when corrected for stage, are uniformly lower for black men

Probable Risk Factors

Dietary Fat: diet of Japanese men has less fat and since fat content of Japanese diet has increased so has incidence of Pca
Hormones: testosterone is necessary for normal prostate epithelium to grow and early prostate cancer has been shown to be endocrine dependent

Potential Risk Factors

Cadmium: trace mineral found in cigarette smoke and alkaline batteries, high levels in those working with welding and electroplating occupations, weak association
Vitamin A: or retinol is fat soluble that is essential for normal differentiation of epithelial cells, physiologic growth, visual function, and reproduction
Vitamin D: Pca more common in Northern countries as compared to those closer to equator, mortality rates are inversely proportional to UV radiation, which is necessary for synthesis of Vit D

Pathology of Adenocarcinoma of Prostate

Prostatic Intraepithelial Neoplasia

Consists of architecturally benign prostatic acini or ducts lined by cytologically atypical cells
Divided into low grade PIN(PIN 1) and high grade PIN(PIN2 and PIN3)
Low grade PIN should not be commented on in diagnostic reports since difficult to distinguish from benign and no increased risk of carcinoma on repeat biopsy
In prostates with carcinoma, there is an increase in the size and number of high grade PIN foci as compared with prostates without carcinoma
Also with increasing number of multifocal high grade PIN, there are a greater number of multifocal carcinomas
When high grade PIN is found on biopsy, there is a 30% to 50% risk of finding carcinoma on subsequent biospsy
PIN itself does not give rise to an elevated PSA
Repeat biopsy if high grade PIN found on needle biopsy
It appears that high grade PIN is a precursor lesion to many peripheral intermediate grade to high grade adenocarcinomas of prostate, PIN need not be present for carcinoma to arise

Adenocarcinoma

Location

Spread of Tumor

Perineural invasion by itself does not worsen prognosis because perineural invasion merely represents extension of tumor along a plane of decreased resistance and not invasion into lymphatics
Most common sites of mets are lymph nodes, followed by bone mets, lung mets extremely uncommon, bladder, liver, adrenal

Tumor Volume

In general, the size of a prostate cancer correlates with its extent
Transition zone tumors in general penetrate the capsule at larger volumes than peripheral zone tumors, as result of their lower grade and greater distance from edge of gland

Grade

Gleason System: both primary(predominant) and secondary(second most prevalent) architectural patterns are identified and assigned a grade from 1 to 5, with 1 being most differentiated and 5 least differentiated
Gleason sum 7 tumors have a significantly worse prognosis than Gleason 5 to 6 cancers, although they are not as aggressive as Gleason 8 to 10 cancers

Ultrasound of Prostate and Biopsy

Transrectal US

Most important finding is a hypoechoic peripheral zone lesion
More subtle indications of carcinoma, including bulging or irregularity of prostatic capsule, extension of hypoechoic areas from the central zone into seminal vesicle, or any area corresponding to an abnormal DRE

Diagnosis and Staging of Prostate Cancer

DRE

Because of significant risk of prostate cancer, prostate biopsy should be recommended for all men who have DRE abnormalities, regardless of PSA because 25% of men with cancer have PSA less than 4

PSA

Member of kallikrein gene family
Serine protease produced by prostatic epithelium and periurethral glands in the male
Secreted into seminal fluid and is involved in liquefaction of seminal coagulum
PSA bound to alpha₁-antichymotrypsin and alpha₂-macroglobulin
Clearance of complexed PSA is thought to be cleared by liver
Half life is 2-3 days
Finasteride has been shown to decrease PSA levels by 50% after 12 mos, baseline PSA before initiation of treatment and should follow serial PSA measurements

Age Specific PSA

PSAD

PSAD of 0.15 or greater has been proposed as a threshold for recommending prostate biopsy in men with PSA between 4.0 and 10

PSA Velocity

Free PSA

Shown that men with prostate cancer have a greater fraction of serum PSA complexed to ACT-lower percentage of total PSA that is free-than men without prostate cancer
A free/total PSA cutoff of 0.18 or less significantly improved the ability to distinguish cancer and noncancer
Catalona: maintaining a sensitivity for detecting 90% among men with PSA between 4-10 and a nonsuspicious DRE, found that a free PSA of 23% or less would eliminate 31% unnecessary biopsies in men with prostate glands larger than 40cm³, wheras, a free PSA cutoff of 14% or less would eliminate 79% unnecessary biopsies in men with glands less than 40cm³

Staging

T1 clinically unapparent tumor-not palpable or visible by imaging
T1a tumor found incidentally at TUR; 5% or less of tissue is cancerous
T1b more than 5% is cancerous
T1c tumor found by needle biopsy because of elevated PSA
T2 palpable tumor confined to prostate
T2a tumor involves half of a lobe or less
T2b tumor involves more than half of lobe but not both lobes
T2c tumor involves both lobes
T3 palpable tumor extending through prostate capsule and or involving seminal vesicle
T3a unilateral extracapsular extension
T3b bilateral extracapsular extension
T3c tumor invades seminal vesicle
T4 tumor is fixed or invades adjacent structures other than seminal vesicles
T4a tumor invades bladder neck and/or external sphincter and/or rectum
T4b tumor invades levator muscles and/or fixed to pelvic sidewall

Clinical and Pathological Staging

Important pathological criteria that are predictive of prognosis after radical prostatectomy are tumor grade; surgical margin status; and presence of extracapsular disease, seminal vesicle invasion or involvement of pelvic lymph nodes
As general guidelines, majority of men(70-80%) with PSA values less than 4 have pathologically organ confined disease
More than 50% of men with PSA greater than 10 already have established capsular penetration
Most men(75%) with serum PSA greater than 50 have positive lymph node