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Risk factors for Prostate cancer?
- Family history
- African descent
- Higher age
Pathology of Prostate cancer?
- More than 95% of the prostate cancers are adenocarcinomas.
- The cytologic characteristics of CaP include hyperchromatic, enlarged nuclei with prominent nucleoli
- Cytoplasm is often abundant; thus, nuclear-to-cytoplasmic ratios are not often helpful in making a diagnosis of CaP, unlike their usefulness in diagnosing many other neoplasms
- Normal prostatic glands always have a basal cell layer. Prostate adenocarcinoma never has a basal cell layer.
- If the diagnosis of CaP is in question, high molecular weight keratin immunohistochemical staining is useful, as it preferentially stains basal cells. Absence of staining is thus consistent with CaP
Types of Prostate cancer?
- 1. Adenocarcinoma (95%)
- - Acinar Adenocarcinoma
- - Intraductal adenocarcinoma - rare aggressive varient.
- 2. Non-adenocarcinomas (<5%)
Most common site of distant metastasis in carcinoma prostate?
- The axial skeleton is the most usual site of distant metastases, with the lumbar spine being most frequently implicated
- The next most common sites in decreasing order are proximal femur, pelvis, thoracic spine, ribs, sternum, skull, and humerus.
- CaP are typically osteoblastic. (RCC are usually osteolytic)
Clinical features of Carcinoma Prostate?
- Symptoms –
- The large majority of patients with early-stage CaP are asymptomatic.
- The presence of symptoms often suggests locally advanced or metastatic disease.
- Obstructive or irritative voiding complaints can result from local growth of the tumor into the urethra or bladder neck or from its direct extension into the trigone of the bladder. Much more commonly, however, such symptoms are attributable to coexisting BPH.
- Metastatic disease to the bones may cause bone pain. Soft tissuemetastases (eg, lung and liver) are rare at the time of initial presentation.
- Metastatic disease to the vertebral column with impingement on the spinal cord may be associated with symptoms of cord compression, including paresthesias and weakness of the lower extremities and urinary or fecal incontinence.
- Signs –
- DRE - Induration or nodularity of prostate.
- Obliteration of median sulcus and the rectal mucosa is tethered to the gland (rectal mucosa cannot be moved over the prostate).
- Locally advanced disease with bulky regional lymphadenopathy may lead to lymphedema of the lower extremities.
- Specific signs of cord compression relate to the level of the compression and may include weakness or spasticity of the lower extremities and a hyperreflexic bulbocavernosus reflex.
Short note on PSA? [TU 56,63,64,70,5/4, 63/4, 61/4]
- PSA is a serine protease in the human kallikrein (hK) family produced by benign and malignant prostate tissues
- PSA is prostate specific, not prostate cancer specific. Other prevalent conditions such as BPH and prostatitis—as well as urethral instrumentation can raise PSA.
- PSA is not able to diagnose Prostate cancer. It only estimates the risk of prostate cancer.
- Normal PSA value - ≤4 ng/mL
- Positive predictive value of a serum PSA between 4 and 10 ng/mL is approximately 20–30%. For levels in excess of 10 ng/mL, the positive predictive value increases from 42% to 71.4%.
- Use of medications such as 5α-reductase inhibitors (including the 1 mg finasteride formulation marked for alopecia as Propecia) must be ascertained, as these medications can artificially lower the PSA by approximately 50%.
What is PSA Kinetics?
Patients whose serum PSA increases by 0.75 ng/mL per year appear to be at an increased risk of harboring cancer. Very rapid PSA increases may be indicative of prostatitis (symptomatic or otherwise) rather than cancer
What is PSA density?
The ratio of PSA to gland volume is termed the PSA density. Some investigators advocate prostate biopsy only if the PSA density exceeds 0.1 or 0.15. The positive predictive value of PSA density is slightly higher than the use of a PSA level >4 ng/ mL
What is PCA3?
Prostate cancer antigen 3 (PCA3) is a noncoding, prostate-specific mRNA, which is overexpressed in the majority of prostate cancers
- Prostate biopsy is performed under TRUS guidance using a spring-loaded biopsy device coupled to the imaging probe.
- For a prostate volume of 30-40 mL, > 8 cores should be sampled. Ten to 12 core biopsies are recommended of the peripheral zone, with > 12 cores not being significantly more conclusive.
- Sextant biopsy is no longer considered adequate.
- On baseline biopsies, the sample sites should be bilateral from apex to base, as far posterior and lateral as possible in the peripheral gland. Additional cores should be obtained from suspect areas by DRE/TRUS.
- Fine-needle aspiration biopsy is no longer recommended.
- Do not use transurethral resection of the prostate as a tool for cancer detection.
- Prostate biopsy is usually performed using local anesthesia and preprocedure antibiotic prophylaxis (usually a fluoroquinolone).
Indication of repeat biopsy after previously negative biopsy?
- Rising and/or persistently elevated PSA
- Suspicious DRE
- Atypical small acinar proliferation
- Extensive (multiple biopsy sites, i.e., > 3) high grade prostatic intraepithelial neoplasia (HGPIN)
- A few atypical glands immediately adjacent to high grade prostatic intraepithelial neoplasia
- Intraductal carcinoma as a solitary finding, > 90% risk of associated high-grade prostate carcinoma
- Positive multiparametric MRI findings
Gleason System for prostate cancer?
The system relies on the low-power appearance of the glandular architecture under the microscope. Pathologists assign Primary and Secondary Grades –
- Primary grade - the pattern of cancer that is most commonly observed
- Secondary grade - the second most commonly observed pattern in the specimen.
- Grades range from 1 to 5 If the entire specimen has only one pattern present, then both the primary and secondary grade are reported as the same grade (eg, 3 + 3). Gleason grades ranged from 1 to 5, and Gleason scores thus ranged from 2 to 10. Gleason patterns 1 and 2 are rarely assigned. Gleason pattern 3 (low-grade), Gleason pattern 4 (intermediate grade) Gleason pattern 5 (high-grade)
- Gleason score 7 tumors, those assigned 4 + 3 are more aggressive than those read as 3 + 4.
- If one pattern is present, it needs to be doubled to yield the Gleason score.
- Gleason scores of 2–4, 5–7, and 8–10 corresponded to well-, moderately, and poorly differentiated tumors, respectively.
TNM staging of Prostate Carcinoma?
- T1 Clinically inapparent tumour not palpable or visible by imaging
- T1a ≤5% of tissue in resection for benign disease has cancer, normal DRE
- T1b >5% of tissue in resection for benign disease has cancer, normal DRE
- T1c Detected from elevated PSA alone, normal DRE and imaging
- T2 Tumour confined within the prostate
- T2a Tumour involves one half of one lobe or less
- T2b Tumour involves more than half of one lobe, but not both lobes
- T2c Tumour involves both lobes
- T3 Tumour extends through the prostatic capsule
- T3a Extracapsular extension on one or both sides
- T3b Seminal vesicle involvement on one or both sides
T4 Tumor directly extends into bladder neck, sphincter, rectum, levator muscles, or into pelvic sidewall
N1 Metastasis in a regional lymph node or nodes
- M1a Distant metastasis in nonregional lymph nodes
- M1b Distant metastasis to bone
- M1c Distant metastasis to other sites
Clinical Risk groups of Prostate cancer?
- Low risk: PSA ≤10, Gleason ≤6, and clinical stage T1 or T2a.
- Intermediate risk: PSA 10–20, Gleason 7, or clinical stage T2b.
- High risk: PSA >20, Gleason 8–10, or clinical stage T2c or T3a.
Chemoprevention of Prostate cancer?
Is screening of Prostate cancer beneficial?
- Disadvantages - leads to overdiagnosis and overtreatment. Some prostate cancer do not cause morbidity or mortality even when they are untreated.
- Advantages - reduces the risk of dying from prostate cancer.
- PLCO trial (Prostate, Lung, Colorectal and Ovarian cancer screening trial)
Treatment of Prostate cancer?
- Watchful waiting/Active Surveillance
- Radical Prostatectomy
- Radiation therapy—external beam therapy, brachytherapy
Highlight the controversies in PSA. How will you treat an elderly gentleman aged 75 years having carcinoma of prostate with stage T2b. [TU 2066/8]
What is Active Surveillance and watchful waiting?
Offer active surveillance to patients with the lowest risk of cancer progression (> 10 years life expectancy, cT1/2a, PSA < 10 ng/mL, biopsy Gleason score ≤ 6)
Offer watchful waiting to patients not eligible for local curative treatment and those with a shortlife expectancy
When should be screening for prostate cancer be started?
- Annual screening if PSA is >2.5ng/ml, family history of prostate cancer, increasing age or African descent
- If low risk, every 2 years
At what age the screening for prostate cancer should be stopped?
It should be stopped based on life expectancy and performance status; men who have a life-expectancy of < 15-years are unlikely to benefit.
What is Radical Prostatectomy?
- Removal of the entire prostate gland between the urethra and bladder, and resection of both seminal vesicles, along with sufficient surrounding tissue to obtain negative margins.
- Bilateral pelvic lymph node dissection.
- Nerve-sparing surgery may be attempted in pre-operatively potent patients with low risk of extracapsular disease (T1,T2a, GS ≤ 6 and PSA < 10 ng/mL)
- In intermediate- and high-risk disease, use multiparametric MRI as a decision tool to select patients for nerve-sparing procedures.
- Do not offer neoadjuvant hormonal therapy before RP.
- Do not offer adjuvant hormonal therapy for pN0.
Diagnosis of recurrent disease?
Three consecutive rises in serum PSA of at least 2 ng/mL greater than the nadir level
Androgen ablation therapy for prostate cancer?
- Pituitary - GnRH or LHRH agonists - goserelin, triptorelin, histrelin, and leuprolide
- Adrenal - Ketoconazole, Aminoglutethimide, Abiraterone
- Testicle – Orchidectomy
- Androgen receptor antagonists (Prostate cell) – Flutamide, bicalutamide
Treatment of metastatic disease?
Initial endocrine therapy - LHRH agonists allow induction of androgen deprivation without orchiectomy or administration of diethylstilbestrol.