Marion Swall, MIV USC School of Medicine

Epidemiology Prostate cancer is the most common cancer & #2 cancer killer in American men Approx 190,000 cases will be diagnosed annually Approx 27,000 deaths will occur Clinically ranges from a well differentiated tumor to an aggressive cancer with substantial invasive and metastatic potential.

Screening Prostate cancer used to be detected by digital rectal examination (DRE) findings of asymmetric areas of induration or frank nodules Now, prostate cancer is usually detected by an elevated serum PSA & is asymptomatic at presentation PSA >10 ng/mL — Prostate biopsy is uniformly recommended. 50% probability of cancer PSA 4 to 10 ng/mL — Prostate biopsy is advised. Specificity is lower, 20% probability of cancer PSA > 2.6 ng/mL & if PSA Velocity is ≥ 0.75 ng/mL per year – Prostate biopsy is advised PSA velocity >2 ng/ml per year is high risk for life threatening cancer

Diagnosis Prostate biopsy is the gold standard Transrectal ultrasonography (TRUS) biopsy is a relatively simple procedure done in the office Transrectal ultrasound in sagittal plane demonstrating hyperechoic biopsy tracts (arrows) evenly spaced throughout the gland.

Staging Staging is critical to guide treatment options given high morbidity of therapy. Endorectal coil MRI & TRUS with staging biopsy can be used to assess the local extent of disease. US shows an extensive, hypoechoic T3 tumor with capsular irregularity on the right and posteriorly (arrowheads) US also suggests infiltration into the rectal wall (arrow).

Staging Continued Endorectal coil MRI provides a more accurate estimate of seminal vesicle involvement or extraprostatic extension Endorectal MRI in a patient with extensive prostate carcinoma showing a bulge in the capsular outline on the right side. This is a stage T3 tumor.

Treatment Options Depending on stage, management includes: Radical Prostatectomy External Beam Radiation Therapy Brachytherapy, Androgen Deprivation Therapy (ADT) Chemotherapy Active Surveillance Ablation Or the new ablation therapy… HIFU

HIFU or Hooey? High-Intensity Focused Ultrasound (HIFU ) pulses energy into an area about the size of a grain of rice creating a sharply delineated point of increased temperature, melting cell membrane lipids and denaturing proteins. HIFU is currently approved in Europe and South America Targeting is planned to avoid the urinary sphincter, rectum, and the neurovascular bundles Complications include urinary incontinence (6%), UTI (7%), obstruction (14%), pelvic pain (6%) & significant erectile dysfunction in 57%. Failure-free survival rates at five & seven yrs were 66 & 59% in T1 & T2 cancers However, pathologic involvement is often more extensive than on imaging Studies suggests that there is a substantial risk of under treatment of biologically significant disease using the focal ablation, emphasizing the need for careful patient selection based on estimated life expectancy and a thorough pretreatment biopsy scheme.

So what happened? HIFU didn’t work External Beam Radiation didn’t work Androgen Deprivation Therapy didn’t work Chemical castration didn’t work Now what?

Distant metastasis Hematogenous spread of prostate cancer cells is common with tumor growth preferentially occurs in bones of the axial skeleton, where red marrow is most abundant Metastatic lesions in bone are frequently symptomatic, causing pain, debility, and functional impairment Radionuclide bone scan with technetium-99m advised in patients with PSA levels >10 ng/mL

Radionuclide Bone Scan

Bone Scan Findings Multiple focal areas of increased radiotracer uptake (hot spots) on RN bone scan are classic for metastatic disease. Metastases appear as hot spots on RN bone scan due to increased osteoblastic activity. RN bone scans are very sensitive for detecting osteoblastic activity, but are non- specific, osteolytic & osteosclerotic metastases present similarly. Fractures, arthritis, and tumors all present as hot spots. Note: the tracer is cleared through the urine, hence the "hot" bladder.

The Superscan With diffuse bone metastases, a "superscan" may be seen. This superscan demonstrates high uptake throughout the skeleton, with poor or absent renal excretion of the tracer.

What do you see?

Ivory Vertebra Note sclerotic vertebral body of normal size at L2 Osteosclerotic metastases are most common from prostate & breast cancer Other possibilities include lymphoma, vertebral hemangioma, or Paget's disease. Osteosclerotic vertebra decreased in height likely to be a compression or healing vertebral fracture.

What do you see?

Femoral Findings The distal femur demonstrates an eccentric, sclerotic lesion with periosteal reaction at the edge of the lesion in the form of a Codman triangle. A Codman triangle is an aggressive pattern of periosteal reaction, but aggressive is not synonymous with malignant. Codman triangle occurs with malignant bone tumors and metastases, but also with osteomyelitis and/or hemorrhage.

The End Manifestations of advanced prostate cancer include: anemia, bone marrow suppression, weight loss, pathologic fractures, spinal cord compression, pain, hematuria, ureteral and/or bladder outlet obstruction, urinary retention, chronic renal failure, urinary incontinence, and symptoms related to bony or soft- tissue metastases. Life expectancy now 9 months to 2 years