In 2019, prostate cancer was diagnosed in 174,650 men in the United States-an incidence that is about 60% as high as breast cancer incidence. A decline in routine PSA testing has led to fewer cases. About 31,620 men died of prostate cancer in 2018. The early diagnosis of cancers in mildly symptomatic men found on screening to have elevated serum levels of PSA has complicated management. Like most other cancers, incidence is age-related. The disease is more common in blacks than whites. Symptoms are generally similar to and indistinguishable from those of prostate hyperplasia, but those with cancer more often have dysuria and back or hip pain. On histology, 95% are adenocarcinomas. Biologic behavior is affected by histologic grade (Gleason score).
In contrast to hyperplasia, prostate cancer generally originates in the periphery of the gland and may be detectable on DRE as one or more nodules on the posterior surface of the gland, hard in consistency and irregular in shape. Those with a negative DRE and PSA ≤4 ng/mL may be followed annually. Those with an abnormal DRE or a PSA >10 ng/mL should undergo transrectal ultrasound (TRUS)-guided biopsy or MRI-directed biopsy. Those with normal DRE and PSA of 4.1-10 ng/mL may be handled differently in different centers. Some would perform TRUS and biopsy any abnormality or follow if no abnormality were found. Some would repeat the PSA in a year and biopsy if the increase over that period were >0.75 ng/mL. Other methods of using PSA to distinguish early cancer from hyperplasia include quantitating bound and free PSA and relating the PSA to the size of the prostate (PSA density). Perhaps one-quarter of persons with prostate cancer do not have PSA elevations.
Lymphatic spread is assessed surgically; it is present in only 10% of those with Gleason grade 5 or lower and in 70% of those with grade 9 or 10. PSA level also correlates with spread; only 10% of those with PSA <10 ng/mL have lymphatic spread. Bone is the most common site of distant metastasis. Whitmore-Jewett staging includes A: tumor not palpable but detected at TURP; B: palpable tumor in one (B1) or both (B2) lobes; C: palpable tumor outside capsule; and D: metastatic disease.
| TREATMENT | ||
Prostate CarcinomaFor pts with stages A through C disease, surgery (radical retropubic prostatectomy) and radiation therapy (conformal three-dimensional fields) are said to have similar outcomes; however, most pts are treated surgically. Both modalities are associated with impotence. Surgery is more likely to lead to incontinence. Radiation therapy is more likely to produce proctitis, perhaps with bleeding or stricture. Addition of hormonal therapy (goserelin) to radiation therapy of pts with localized disease appears to improve results. Pts usually must have a 5-year life expectancy to undergo radical prostatectomy. Stage A pts have survival identical to age-matched controls without cancer. Stage B and C pts have a 10-year survival of 82% and 42%, respectively. Pts treated surgically for localized disease who develop rising PSA may undergo Prostascint scanning (antibody to a prostate-specific membrane antigen). If no uptake is seen, the pt is observed. If uptake is seen in the prostate bed, local recurrence is implied and external beam radiation therapy is delivered to the site. (If the pt was initially treated with radiation therapy, this local recurrence may be treated with surgery.) However, in most cases, a rising PSA after local therapy indicates systemic disease. It is not clear when to intervene in such pts. Treatment is often initiated if the PSA doubling time is <10 months. For pts with clinically apparent metastatic disease or rapidly rising PSA, androgen deprivation is the treatment of choice. Surgical castration is effective, but most pts prefer to take leuprolide, 7.5 mg depot form IM monthly (to inhibit pituitary gonadotropin production), plus flutamide, 250 mg PO tid (an androgen receptor blocker). The value of added flutamide is debated. Alternative approaches include adrenalectomy, hypophysectomy, estrogen administration, and medical adrenalectomy with aminoglutethimide. The median survival of stage D pts is 33 months. Pts occasionally respond to withdrawal of hormonal therapy with tumor shrinkage. Not all pts who develop disease progression on hormonal therapy are resistant to androgen deprivation. Second hormonal manipulations act by blocking androgen production in the tumor; abiraterone, a CYP17 inhibitor that blocks androgen synthesis and enzalutamide and apalutamide, structurally related antiandrogens, improve overall survival. Many pts who progress on hormonal therapy have androgen-independent tumors, often associated with genetic changes in the androgen receptor and new expression of bcl-2, which may contribute to chemotherapy resistance. Chemotherapy is used for palliation in prostate cancer. Mitoxantrone, estramustine, and taxanes, particularly docetaxel and cabazitaxel, appear to be active single agents, and combinations of drugs are being tested. Chemotherapy-treated pts are more likely to have pain relief than those receiving supportive care alone. Sipuleucel-T, an active specific immunotherapy, improves survival by about 4 months in hormone-refractory disease without producing any measureable change in the tumor. Bone pain from metastases may be palliated with strontium-89 or samarium-153. Bisphosphonates decrease the incidence of skeletal events. |
Finasteride and dutasteride have been shown to reduce the incidence of prostate cancer by 25%, but no effect on overall survival has been seen. In addition, the cancers that do occur appear to be shifted to higher Gleason grades, but the clinical course of disease does not seem to be altered.