Prostate cancer is the most common noncutaneous cancer among males, making the diagnosis and staging of this cancer of great medical and public interest. Although prostate cancer can be slow growing, the disease nonetheless accounts for almost 10% of cancer-related deaths in males, with thousands of men dying of prostate cancer each year (see the image below).

Screening controversies

Digital rectal examination (DRE) and PSA evaluation are the two components necessary for a modern screening prostate cancer program. However, there is controversy regarding screening.

Advocates of screening for prostate cancer believe that early detection is crucial to finding organ-confined disease and to reducing the likelihood of mortality. When symptoms develop or when DRE results become positive, most cases have already advanced beyond organ-confined disease. However, those who do not advocate screening worry that screening will detect cancers that are not biologically significant (ie, in patients who will die with prostate cancer rather than from it).

The American Cancer Society (ACS), ^[1] the American Urological Association (AUA), ^[2] and the National Comprehensive Cancer Network (NCCN), ^[3] have issued guidelines that differ on specific points but agree on the value of prostate cancer screening in selected populations, for patients who agree to screening after a discussion of the risks and benefits. In contrast, the U.S. Preventive Services Task Force (USPSTF) recommends against PSA-based prostate cancer screening, ^[4] and the European Society for Medical Oncology (ESMO) recommends against population-based PSA screening for prostate cancer on the grounds that it reduces prostate cancer mortality at the expense of overdiagnosis and overtreatment. ^[5]

Signs and symptoms

With the advent of PSA screening, patients report the following local symptoms:

• No symptoms (47%)
• Urinary frequency (38%)
• Urinary urgency (10%)
• Decreased urine stream (23%)
• Hematuria (1.4%)

Metastatic symptoms of prostate cancer include the following:

• Weight loss and loss of appetite
• Bone pain, with or without pathologic fracture
• Lower extremity pain and edema
• Uremic symptoms

Diagnosis

Laboratory studies

• PSA screening: Controversy exists regarding PSA level cutoffs and reference ranges
• DRE: Serial examinations are best; clues to the patient’s condition in conjunction with PSA levels include presence of a nodule, as well as asymmetry, texture difference(s), and bogginess of the prostate, seminal vesicles, and adjacent organs
• Biopsy and histologic examination: These aid in the diagnosis and help to determine the Gleason score; a biopsy can also help differentiate a cyst or calculus from cancer foci

Imaging studies

• Computed tomography (CT) scanning: To assess extension into the bladder and lymph nodes for staging the cancer or for considering pretreatment lymph node sampling
• Endorectal magnetic resonance imaging (MRI): To localize cancer within the prostate and seminal vesicles; to help in local staging
• Bone scanning: To evaluate bone metastasis
• MRI: To determine the etiology of questionable lesions found on bone scans
• Transrectal ultrasonography: To examine the prostate for hypoechoic areas, which are commonly associated with cancers but are not specific enough for diagnostic purposes

Men with PSA levels above 10 ng/mL, high-grade histology (Gleason score of ≥7), or physical findings suggesting stage T3 disease should probably undergo a staging CT scan and bone scan. Neither CT scanning nor MRI can be used to determine if lymph nodes are reactive or contain malignant deposits, unless the nodes are significantly enlarged and a percutaneous biopsy can be performed.

TNM staging and grouping of prostate cancer

Tumor 

• T – Primary tumor
• TX – Primary tumor cannot be assessed
• T0 – No evidence of primary tumor
• T1 – Clinically inapparent tumor not palpable or visible by imaging
• T1a – Tumor incidental histologic finding in 5% or less of tissue resected
• T1b – Tumor incidental histologic finding in greater than 5% of tissue resected
• T1c – Tumor identified by needle biopsy (due to elevated prostate-specific antigen [PSA] level); tumors found in 1 or both lobes by needle biopsy but not palpable or reliably visible by imaging
• T2 – Tumor confined within prostate
• T2a – Tumor involving less than half a lobe
• T2b – Tumor involving 1 lobe or less
• T2c – Tumor involving both lobes
• T3 – Tumor extending through the prostatic capsule; no invasion into the prostatic apex or into, but not beyond, the prostatic capsule
• T3a – Extracapsular extension (unilateral or bilateral)
• T3b – Tumor invading seminal vesicle(s)
• T4 – Tumor fixed or invading adjacent structures other than seminal vesicles (eg, bladder neck, external sphincter, rectum, levator muscles, pelvic wall)
• NX – Regional lymph nodes (cannot be assessed)
• N0 – No regional lymph node metastasis
• N1 – Metastasis in regional lymph node or nodes

Regional lymph nodes 

Regional lymph nodes are assessed via surgical removal or through biopsy of the pelvic lymph nodes, including the obturator chain. The surgical boundaries include the bifurcation of the common iliac, the obturator nerve, and the node of Cloquet.

Distant metastasis 

• PM1c – More than 1 site of metastasis present
• MX – Distant metastasis cannot be assessed
• M0 – No distant metastasis
• M1 – Distant metastasis
• M1a – Nonregional lymph node(s)
• M1b – Bone(s)
• M1c – Other site(s)

The TNM system for grouping prostate cancer is based on the following 5 key pieces of information ^[7] :

• The extent of the primary tumor (T category)
• Whether the cancer has spread to nearby lymph nodes (N category)
• The absence or presence of distant metastasis (M category)
• The PSA level at the time of diagnosis
• The Gleason score, based on prostate biopsy (or surgery)

Stage I - Cancer found in the prostate only

• T1, N0, M0, Gleason score 6 or less, PSA less than 10 or
• T2a, N0, M0, Gleason score 6 or less, PSA less than 10

Stage II (IIa and IIb) - Cancer is more advanced than stage I, but has not spread outside the prostate

Stage IIa - One of the following applies:

• T1, N0, M0, Gleason score of 7, PSA less than 20 or
• T1, N0, M0, Gleason score of 6 or less, PSA at least 10 but less than 20or
• T2a or T2b, N0, M0, Gleason score of 7 or less, PSA less than 20

Stage IIb - One of the following applies:

• T2c, N0, M0, any Gleason score, any PSA or
• T1 or T2, N0, M0, any Gleason score, PSA of 20 or more or
• T1 or T2, N0, M0, Gleason score of 8 or higher, any PSA

Stage III - Cancer has spread outside the prostate and may have invaded the seminal vesicles

• T3, N0, M0, any Gleason score, any PSA

Stage IV - Cancer has spread outside the prostate, into surrounding pelvic organs, into lymph nodes, or as distant metastasis outside the pelvis

• T4, N0, M0, any Gleason score, any PSA or
• Any T, N1, M0, any Gleason score, any PSA or
• Any T, any N, M1, any Gleason score, any PSA