Prostate Carcinoma

Description

Prostate carcinoma, commonly referred to as prostate cancer, is a malignant neoplasm that originates from the glandular epithelium of the prostate. It is among the most common malignancies in men worldwide, and the incidence increases with age. The tumour is often asymptomatic in early stages and is typically slow-growing. However, aggressive variants exist that may metastasise to bones and other organs, causing significant morbidity and mortality.

Pathogenesis

The pathogenesis of prostate carcinoma is multifactorial and typically involves a combination of genetic and environmental factors. Key pathogenetic mechanisms involve androgen signalling, as the prostate gland’s growth and development are androgen-dependent, and genomic changes like mutations, copy number alterations, and chromosomal rearrangements. The most common genetic alterations are observed in genes such as PTEN, TP53, and RB1. TMPRSS2-ERG gene fusions are also found in approximately half of prostate cancers.

Epidemiology, Risk Factors & Associations

• Prostate cancer is the second most common cancer among men worldwide, and it’s the fifth leading cause of cancer death in men.
• It’s rarely seen before age 40, but the incidence increases significantly after age 50.
• The highest incidence rates are found in Australia/New Zealand, Northern America, and Northern Europe, while the lowest rates are in Asia.
• Having a first-degree relative (father or brother) with prostate cancer approximately doubles a man’s risk. Mutations in the BRCA1 and BRCA2 genes also increase the risk (BRCA2 more than BRCA1).
• Prostate cancer is more common and more likely to be aggressive in Black men than in men of other races.
• A diet high in red meat and high-fat dairy products, as well as obesity, have been associated with an increased risk of prostate cancer.

Subtypes

Prostate cancer primarily manifests as acinar adenocarcinoma, making up to 90-95% of cases. However, there are several recognised subtypes of prostate carcinoma, each with distinct histopathological characteristics:

• Acinar adenocarcinoma: This is the most common subtype and is derived from the glandular cells of the prostate. On microscopic examination, these tumours show infiltrative, small, tight clusters or individual cells, with prominent nucleoli.
• Ductal adenocarcinoma: Accounting for approximately 1% of all prostate cancers, ductal adenocarcinoma tends to be more aggressive than acinar adenocarcinoma. The cells of ductal adenocarcinoma form tall, columnar cells and pseudostratified layers, with a papillary or cribriform pattern.
• Neuroendocrine (small cell) prostate carcinoma: This is a rare and aggressive subtype, typically occurring in men who have been treated for acinar adenocarcinoma. Neuroendocrine prostate carcinoma does not produce PSA, making it harder to detect with routine testing and is more resistant to hormone therapy. The tumour cells are small with scant cytoplasm, and the growth pattern is sheet-like or rosette-like.
• Transitional cell (urothelial) carcinoma: This subtype arises from the urothelial cells lining the prostate and typically extends from the bladder. These cancers often grow faster and are more likely to spread than acinar adenocarcinoma. Histologically, the tumour shows papillary or flat growth of cells that resemble urothelial cells of the bladder.
• Intraductal carcinoma of the prostate: This is a rare and aggressive form of prostate cancer characterised by growth of carcinoma cells within large-calibre ducts of the prostate. The diagnosis is based on the combination of the following three features: a solid or dense cribriform or loose pattern, a prominent nucleolus in at least some cells, and preservation of basal cells.
• Prostate carcinoma with squamous differentiation: Squamous differentiation can be observed in 0.5–1% of prostate carcinomas. The tumour cells resemble those in squamous cell carcinomas from other organ sites. This subtype has been associated with poor prognosis.

Clinical Features

In the early stages, prostate carcinoma is often asymptomatic, frequently discovered during routine screening (e.g., PSA testing). In more advanced stages, or if the tumour is near the outer part of the prostate, symptoms might include:

• Difficulty with urination
• Decreased force in the stream of urine
• Blood in the urine or semen
• Bone pain (in cases of metastasis)
• Erectile dysfunction
• Abnormal digital rectal exam

Complications

The complications of prostate carcinoma include urinary incontinence, erectile dysfunction (post-treatment), metastasis to bones (leading to pain and fracture), spinal cord compression, and renal failure due to ureteral obstruction.

Prostate cancer can metastasise by:

• Local invasion – typically into the bladder and seminal vesicles; urethral and rectal involvement are rare
• Lymphatic spread – pelvic nodes first followed by para-aortic and inguinal nodes
• Haematogenous metastases: bone (90%), lung (~45%), liver (~25%), pleura (~20%), adrenal glands (~15%)

Treatment-related complications include:

• Urethral stricture
• Nervous injury (urinary incontinence and impotence)
• Cystitis and proctitis

Pathological Features

Histopathology

The most common type of prostate carcinoma is acinar adenocarcinoma, which comprises over 90% of all prostate cancers. It is characterised by small, crowded, irregular glands infiltrating between benign glands. The cancer cells have prominent nucleoli.

Pathologic specimens are graded using the Gleason score, which is the sum of the most prevalent and second most prevalent types of dysplasia, each on a scale of 1 to 5, with 5 being the most dysplastic.

Serology

• Elevated serum prostate-specific antigen (PSA) >4 ng/dL is often the first indication of possible prostate cancer, although it can also be raised in benign prostatic hyperplasia and prostatitis. Cancer elevates the PSA 10 times more than BPH. Higher PSA correlates with more tumour.

Radiological Features

Normal Anatomy

• The normal prostate gland demonstrates homogeneous intermediate to low T1 signal intensity, with high T2 signal intensity in the peripheral zone.
• The zonal anatomy of the prostate gland is best depicted on high-resolution T2-weighted images.

General Features

• Most common location of prostate carcinoma is the peripheral zone of the prostate (70% of cases), followed by transition zone (20-25%) and central zone (5-10%).
• Most prostate cancers enhance early, rapidly and avidly.
• Pattern of spread may be nodular, nodular infiltrative or infiltrative, spreading along capsule (usually non-palpable and non-detectable by US).
• CT usually has limited value.
• Multiparametric MRI (mpMRI) is the imaging method of choice for suspected prostate carcinoma.
  • Antispasmodics (glucagon, buscopan) may reduce bowel motion allowing better assessment of nodes.
  • Endorectal (1.5T) or surface coil (3T) is used.
  • Large field of view T1 and DWI to assess for adenopathy and bony lesions.
  • Multiple DWI B-values which include 0 and >1400 mm/s by default.
• Extracapsular extension criteria on MRI
  • Neurovascular bundle asymmetry
  • Tumour envelopment of the neurovascular bundle
  • Angulated contour of the prostate gland
  • Irregular, spiculated margin
  • Obliteration of the rectoprostatic angle
• Seminal vesicle invasion criteria on MRI
  • Focal low T2 signal intensity of the seminal vesicle (normally high T2 signal)
  • Direct tumour extension from the base to the undersurface of the seminal vesicle
  • Expanded low signal ejaculatory duct with low signal seminal vesicle
  • Contrasting enhancing tissue within the seminal vesicle
• Low signal intensity in the peripheral zone can represent haemorrhage, prostatitis, hyperplastic nodules, or post-treatment sequelae (e.g., as a result of irradiation or hormonal treatment).

MRI

• T2:
  • Peripheral zone cancers appear as a low signal intensity focal lesion in the peripheral zone of the prostate, which is normally high signal.
  • Transitional zone cancers (less common) are homogenous, non-circumscribed hypointensities which have an erased-charcoal appearance
• DWI/ADC:
  • Peripheral zone cancers demonstrate high signal intensity on high b-value images with corresponding low signal on ADC map.
  • Higher grade tumours correlate with lower ADC signal
• T1 Pre-contrast: Evaluate for post-biopsy haemorrhage. T1-weighted images do not allow differentiation of tumour from normal prostate parenchyma. Useful for assessing the contour of the prostate and involvement of the neurovascular bundle.
• T1 Dynamic contrast-enhanced (DCE):
  • Rapid early enhancement (first 10-15 seconds) followed by delayed washout.
  • Enhancement is focal, more intense, asymmetric and earlier than adjacent tissue.
  • Important in increasing detection and differentiation of lesions with PI-RADS DWI classification 3.
  • Small, low-grade tumours may not demonstrate abnormal enhancement.
  • The degree of enhancement on correlates positively with tumour grade.

US

• Transrectal ultrasound typically used for imaged-guided biopsy. Not commonly used for detection or staging.
• B-mode: Most tumours are hypoehoic in the peripheral zone, though can be isoechoic in some cases
• Colour Doppler: Can be hypervascular but absence does not exclude cancer.
• Power Doppler: No advantages over colour doppler

CT

• Useful for staging among patients with intermediate- or high-risk disease.
• Not used for initial detection of cancer.
• Post-contrast: Mass-like PZ enhancement may indicate high-grade (≥ Gleason 4 + 3) cancer

NM

• Bone Scan:
  • Tc-99m MDP planar bone scan: Standard modality for diagnosis of bone metastases (sensitivity 62-89%, specificity 57%). Reflects osteoblastic response in cortex, misses early marrow disease
  • Tc-99m MDP SPECT: Higher sensitivity (92%) and specificity (82%)
• PET/CT: Main role of PET/CT is in primary staging and evaluation for biochemically recurrent disease

Grading and Staging

The Gleason score, ranging from 2 to 10, is used to grade the aggressiveness of prostate cancer based on its microscopic appearance. It’s composed of the sum of two grades (the primary and secondary patterns) each ranging from 1 to 5, making the total score range from 2 to 10. A score of 6 is considered low-grade cancer, 7 is intermediate, and 8 to 10 is high-grade cancer. Gleason 7 and above are considered clinically significant.

• Gleason X: Gleason score cannot be determined
• Gleason 6 or less: The cells are well-differentiated, less aggressive, and appear similar to normal prostate cells.
• Gleason 7: The cells are moderately differentiated; it is further divided into two groups:
  • 3+4=7: Cancer cells still look somewhat similar to normal cells and suggest a better prognosis.
  • 4+3=7: Cancer cells that look more abnormal suggest a worse prognosis.
• Gleason 8-10: The cells are poorly differentiated or undifferentiated, are more aggressive, and do not appear like normal prostate cells.

The Gleason score, along with other factors such as prostate-specific antigen (PSA) levels and the stage of the cancer, can help determine the prognosis and guide treatment options. Higher scores indicate more aggressive cancers.

The TNM (Tumour, Node, Metastasis) system is used to stage prostate cancer.

T Category: Tumour

• T1: The tumour cannot be felt during a digital rectal examination (DRE) and isn’t visible on imaging, but is found during a biopsy done for a raised prostate-specific antigen (PSA) level. It has subcategories:
  • T1a: The cancer is present in 5% or less of the tissue removed.
  • T1b: The cancer is present in more than 5% of the tissue removed.
  • T1c: The cancer is found during a needle biopsy that was done because of a raised PSA.
• T2: The tumour is in the prostate only and can be felt during a DRE or seen on imaging. It has subcategories:
  • T2a: The cancer is in half or less than half of one side (left or right) of the prostate.
  • T2b: The cancer is in more than half of one side (left or right) of the prostate.
  • T2c: The cancer is in both sides of the prostate.
• T3: The tumour has begun to spread outside the prostate and may involve the seminal vesicles. It has subcategories:
  • T3a: The cancer extends outside the prostate but doesn’t involve the seminal vesicles.
  • T3b: The cancer has spread to the seminal vesicles.
• T4: The tumour has spread to tissues next to the prostate other than the seminal vesicles such as the urethral sphincter, rectum, bladder, or pelvic wall.

N Category: Node

• N0: There is no spread to nearby lymph nodes.
• N1: The cancer has spread to nearby lymph nodes.

M Category: Metastasis

• M0: There is no distant spread.
• M1: The cancer has spread to distant parts of the body. It has subcategories:
  • M1a: The cancer has spread to lymph nodes outside of the pelvis.
  • M1b: The cancer has spread to the bones.
  • M1c: The cancer has spread to other sites in the body.

Differential Diagnosis

Imaging-based

Differential for T2-dark lesion in PZ

• Biopsy-related haemorrhage, prostatitis, atrophy, fibrosis
• Prostatitis: This is an infection or inflammation of the prostate that can also raise PSA levels and mimic symptoms.
• Atrophy: Typically wedge-shaped areas of low T2 signal and mildly decreased ADC map signal from loss of glandular tissue (but typically not as low as in cancer). May have contour retraction.
• Fibrosis: Can occur after inflammation, may appear as wedge- or band-shaped low signal on T2WI MR
• Benign prostatic hyperplasia (BPH): BPH is a benign growth of the prostate that can mimic the symptoms of prostate cancer. Enlargement is usually of the central zone, sometimes accompanied by calcification. Multiple circumscribe nodules described as organised chaos may be seen.
• Granulomatosis Prostatitis: A relatively common nodular form of chronic inflammation, usually diagnosed by biopsy. Hypoechoic nodules on a background of diffuse hypoechoic peripheral zone is usually seen. No enhancement on MRI. Gland is typically T2 hypointense.

Management

Treatment decisions for prostate carcinoma depend on several factors, including the stage and grade of the cancer, the patient’s age and general health, and patient preference. Options may include:

• Active surveillance for low-risk cancers
• Surgery (radical prostatectomy)
• Radiotherapy
• Hormone therapy (androgen deprivation therapy)
• Chemotherapy
• Newer treatments like immunotherapy or PSMA-targeted therapy

Referral to a urologist is recommended for diagnostic confirmation (prostate biopsy) and treatment planning.