15 Prostate Cancer
Epidemiology
Almost all cases of prostate cancer (PC) occur in men over the age of 50 years. Having a first-degree relative (father or brother) increases the risk two- to threefold, having two first-degree relatives increases it 5-fold to 11-fold. 1 In the United States, PC is more common in African American men than in white men. It is also associated with diet, hypertension, obesity, lack of activity, a high number of sexual partners, and sexually transmitted diseases. 2
Pathology
Adenocarcinoma arising from the acinar and proximal duct epithelium in the peripheral zone of the prostate making early extracapsular extension frequent. It is multifocal in 85% of cases. 3 , 4 Pathologic grading on Gleason’s scale is an important factor in the prognosis and treatment recommendations. The score of the dominant (>50%) of the biopsy specimen is determined and then added to the score of the next greatest type, as in “Gleason 4+3”:
Gleason 1 = Very close to normal without invasion into normal tissue (rarely seen).
Gleason 2 = Glands are looser and not as uniform as in 1 (rarely seen).
Gleason 3 = Clearly infiltrative neoplasm with invasion into adjacent normal tissue. Glands are irregular in size but can be circumscribed.
Gleason 4 = Glands are fused together with no clear separation with scalloped edges
Gleason 5 = No glandular differentiation and composed of sheets of cells or solid cords or individual cells. No round glands are present. 5 – 7
Most treatable lesions are of Gleason scores of 5 to 7 with the biopsy obtained after an abnormal serum prostate-specific antigen or digital rectal examination. Tumors of Gleason scores of 8 to 10 are advanced lesions where likely only palliative care is given.
Genetics
Diagnosis
Screening is a controversial subject. Serum prostate-specific antigen (PSA) levels are not recommended by the United States Preventative Services Task Force due to the overdiagnosis and overtreatment of PC without increasing overall survival (OS) and most of the cancers diagnosed would be asymptomatic. 8 Unfortunately, the screening cannot discriminate between the aggressive tumors and those that are low grade and unlikely to become aggressive. Given that imaging and serial digital prostate exams are the best ways to detect PC, any suspicious nodule on digital exam should be followed up by a magnetic resonance imaging (MRI) and any suspicious lesions biopsied. Elderly patients or patients with an expected life span of less than 10 years should not be screened. These lesions are graded by the Prostate Imaging – Reporting and Data System (PI-RADS). The latest version, PI-RADSv2, is focused on detection of significant PC, which is Gleason grade 4 or higher with a volume greater than 0.5 mL. The MRI parameters are spelled out in detail in the American College of Radiology publication. 9 , 10 The PI-RADS score ranges from 1 to 5:
1 = Most likely benign.
2 = Clinically significant PC is unlikely to be present.
3 = Presence of PC is equivocal.
4 = PC is likely to be present.
5 = PC is highly likely to be present.
Staging 11
Tumor
T1 = Clinically inapparent. Neither palpable nor present on imaging.
T2 = Palpable or visible tumor within the prostate.
T2a = Less than half of one lobe.
T2b = More than half of one lobe, not both.
T2c = Both lobes.
T3 = Tumor extends through prostate capsule.
T3a = Extracapsular extension.
T3b = Seminal vesical involvement.
T4 = Tumor is fixed or invades adjacent structures other than seminal vesicles.
Lymph Nodes
In intermediate-risk PC with a Gleason score of 7 to 8, 5 to 10% of patients have pelvic lymph node involvement, while those with high-risk PC with a Gleason score of greater than 8 have a 20 to 50% risk.
Metastases
Metastases occur predominantly in bones and lymph nodes but occasionally to liver where it is a hypervascular tumor.
Treatment
Treatment is dependent on the clinical stage, PSA level, Gleason score, age of patient, and presence of metastatic disease.
Clinically Localized Disease
Active surveillance is recommended in those patients who have localized disease that is low grade, PSA < 10, and Gleason score 6, and in younger patients. The repeat MRI should be obtained every 2 years with the PSA level. The psychological effect of knowing that a low-grade tumor is present but nothing is “being treated” is difficult for many patients. Approximately 20% of the active surveillance patients elect to undergo surgery or radiation therapy after 1 year. In patients with low-risk PC, when the doubling time of the PSA is less than 2 years, OS with active surveillance at 8 years is reported to be 85% and disease-specific and metastasis-free survival to be 99%. About 25% of patients were treated by 5 years and 40% by 10 years with the delay associated with a lack of cancer control suggesting that waiting until the PSA doubling time reached 2 years was too late. 12 Patients undergoing active surveillance followed by serial biopsies and intervention determined by the change in biopsy score were treated at a mean of 6.5 years with 40% by 5 years and 59% by 10 years. These patients demonstrated that the delay in therapy did not affect cancer control. 13 These results suggest that diagnosis by PSA alone is insufficient and under-grade the tumor, and serial biopsies are far better at determining the time of intervention. Most physicians are utilizing MRI to follow active surveillance patients with early biopsies.
Surgery
Radical prostatectomy (RP) is an option to active surveillance. The success of the procedure to obtain an R0 resection is due to the experience and skill of the performing urologist. RP compared with watchful waiting (as opposed to active surveillance) reduced the risk of death from PC by 44%, the clinical local recurrence by 66%, and the need for anti-androgenic therapy by 51%. 14 In a large U.S. trial, men with clinically localized PC were randomized to either observation or RP. The study showed that the risk of dying from PC when an RP was performed in aggressive cancers with a PSA > 10 or had aggressive histologic features was reduced and the likelihood of metastases was decreased. 15 This suggests that those patients who undergo RP with an intermediate- or high-risk PC have less risk of metastases and of death when early RP is utilized. Even in those patients who have a Gleason score of 8 to 10, RP has a 42% probability of progression-free survival at 10 years. 16
The most important complications after surgery are incontinence and impotence. Nerve-sparing surgery should decrease the rate of impotence, but the size of the tumor and the experience of the surgeon are the critical determinants. Rates of impotence of 30 to 80% have been reported and incontinence of 16%. 17
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