Prostate cancer (prostate cancer)

Prostate cancer (prostate cancer) is a malignant tumor originating from the glandular epithelium of the alveolar-tubular structures, mainly in the peripheral zone of the prostate, and occurring more often in elderly men. Prostate cancer is usually represented by adenocarcinoma. Before ureteral obstruction, symptoms rarely occur. The diagnosis is suggested by digital rectal examination or determination of PSA concentration and is confirmed by biopsy data.

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Epidemiology

Currently, prostate cancer is the most common oncourological disease, which is the subject of numerous scientific papers, periodicals, textbooks and monographs. Nevertheless, the incidence of prostate cancer is constantly growing; in Western industrially developed countries, this tumor is the second most common in men after bronchogenic lung carcinoma. The United States is the country where prostate adenocarcinoma is most common (with a significant predominance of African Americans among patients). In these patients, prostate cancer displaces bronchial carcinoma from the first place in the scale of causes of death. Mortality from this disease has increased by 16% over the past 25 years. The incidence of prostate cancer in Russia is comparable to that in Asian countries (15-18 people per 100,000 population), but its significant growth has been noted, amounting to almost 50% over the past 15 years. The increase in the incidence rate can also be explained by an increase in the life expectancy of men by 20 years over the past seven decades.

The mortality rate directly caused by the tumor currently amounts to about 30%. In Germany, prostate cancer is the third most common cause of death among men. In Austria, it is the most common malignant tumor in men and the most common cause of death from malignant diseases. In Switzerland, prostate cancer is second only to lung cancer, with about 3,500 new cases and about 1,500 deaths caused by prostate cancer recorded there each year.

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Causes prostate cancer (prostate cancer)

Prostate adenocarcinoma is the most common non-dermatologic cancer in men over age 50 in the United States. In the United States, approximately 230,100 new cases and approximately 29,900 deaths (in 2004) occur each year.

The incidence increases with each decade of life; autopsy studies report a prevalence of 15-60% in men aged 60-90 years, and an increase with age. The average age at diagnosis is 72 years, and more than 75% of all prostate cancer cases are diagnosed in men over 65 years of age. African Americans are at highest risk.

Prostate sarcoma is rare, and occurs more frequently in children. Undifferentiated prostate cancer, squamous cell carcinoma, and ductal transitional carcinoma are also encountered. Hormonal influences contribute to the development of adenocarcinoma, but not other types of prostate cancer.

Prostatic intraepithelial neoplasia (PIN) is a premalignant histologic change. It can be low- or high-grade; high-grade PIN is considered a precursor to invasive cancer.

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Symptoms prostate cancer (prostate cancer)

Prostate cancer usually progresses slowly and rarely causes symptoms until it has spread. In advanced cases, hematuria and obstructive urinary symptoms (eg, straining to urinate, hesitancy, weak or intermittent urinary stream, feeling of incomplete emptying, post-micturition incontinence) may develop. Bone pain may develop due to osteoblastic metastases to bone (usually the pelvis, ribs, vertebral bodies).

Forms

The most widely used classification is the Gleason classification (there are five gradations depending on the degree of loss of cell differentiation). The Gleason score is calculated by summing the two most common categories in the specimen; it has an important diagnostic and prognostic value. The prevalence of the tumor within the prostate and its relation to nearby organs and tissues (category T), the involvement of regional tumor nodes (category N) and the presence of distant metastases (category M) are assessed. When determining the degree of local spread of the process, it is first necessary to determine whether the tumor is limited to the prostate (localized forms of prostate cancer (T1c-T2c) or extends beyond its capsule (T3a-T4b). Regional lymph nodes should be assessed only in cases where this directly affects the treatment tactics - usually when planning radical treatment of prostate cancer (prostate cancer).

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Diagnostics prostate cancer (prostate cancer)

On digital rectal examination (DRE), the prostate may be stony with nodules, but the findings are often normal; indurations and nodules suggest cancer but must be differentiated from granulomatous prostatitis, prostatic calculi, and other prostate diseases. Extension of indurations to the seminal vesicles and limited lateral mobility of the gland suggest localized advanced prostate cancer. Prostate cancer detected by DRE is usually of significant size and extends beyond the capsule in more than 50% of cases.

Prostate cancer screening

Most cases are detected by screening rectal examination and PSA testing, which are usually performed annually in men over 50 years of age. Abnormal findings require histologic confirmation, usually by transrectal ultrasound needle biopsy, which can be performed in the office without general anesthesia. Hypoechoic areas are more likely to represent cancer.

Although there is a trend toward lower prostate cancer mortality and lower rates of advanced disease after the introduction of routine screening, the value of such screening has not been proven. Occasionally, prostate cancer is diagnosed incidentally in a specimen removed during surgery for BPH.

The use of PSA concentration as a screening test is somewhat problematic. It is elevated in 25% to 92% of patients with prostate cancer (depending on tumor volume), but may also be moderately elevated in 30% to 50% of patients with BPH (depending on prostate size and structure), in some smokers, and in the weeks following prostatitis. Concentrations greater than 4 ng/mL have traditionally been considered an indication for biopsy in men over 50 years of age (in younger patients, concentrations greater than 2.5 ng/mL probably warrant biopsy because BPH, the most common cause of elevated PSA, is rare in this age group). Although very high concentrations are diagnostic (suggesting extracapsular extension of the tumor or metastasis) and it is clear that the likelihood of cancer increases with increasing PSA levels, there is no cutoff below which there is no risk of cancer. In asymptomatic patients, the positive predictive value for cancer is 67% for PSA >10 ng/mL and 25% for PSA concentrations of 4-10 ng/mL. Recent observations indicate a cancer prevalence of 15% for PSA <4 ng/mL and 10% for PSA 0.6 to 1.0 ng/mL in men over 55 years of age.

Tumors in patients with lower PSA concentrations tend to be smaller (often <1 mL) and less well differentiated, although well differentiated disease (Gleason score 710) may be present at any PSA. It is possible that 15% of patients with a PSA <4 ng/mL are well differentiated. There is some evidence that a PSA cutoff of 4 ng/mL misses some cancers, but the clinical significance is unclear. There is no evidence that performing biopsy in patients over 50 years of age with a PSA <4 ng/mL improves diagnostic and therapeutic outcome in patients with rapidly increasing PSA concentrations (>2 ng/mL per year). The inherent biology of the tumor may make these patients incurable regardless of early diagnosis.

Assays that measure the ratio of free PSA to total PSA are more specific than standard PSA measurements and may reduce the frequency of biopsies in patients without cancer. Prostate cancer is associated with lower free PSA concentrations; no diagnostic threshold has been established, but in general values < 15-20% require biopsy. Other PSA isoforms and new markers for prostate cancer are under study.

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Definition of staging and differentiation

Prostate cancer staging is based on tumor extension. Transrectal ultrasound can provide information for staging, particularly on capsular extension and seminal vesicle invasion. Increased plasma acid phosphatase, particularly by enzymatic assay, correlates well with the presence of metastases, predominantly to bone and lymph nodes. However, the enzyme may also be elevated in BPH (slightly after vigorous prostate massage), multiple myeloma, Gaucher disease, and hemolytic anemia. Radionuclide bone scanning is performed to detect bone metastases (sometimes detected radiographically). Reverse transcriptase-based polymerase chain reaction (PCR) testing for circulating prostate cancer cells is currently being studied as a staging and prognostic tool.

Differentiation assessment, based on the comparison of tumor structure with normal gland structure, helps to determine tumor aggressiveness. The assessment takes into account the histologic heterogeneity of the tumor. The Gleason score is the most commonly used: the two most common structures are assigned a score from 1 to 5 and 2 points are added (total score: 2-4 = well differentiated, 5-7 = moderately differentiated, and 8-10 = undifferentiated); in another scoring system, <6 points are considered well differentiated, 7 points are moderately differentiated, and 8-10 points are poorly differentiated. The lower the score, the less aggressive and invasive the tumor and the better the prognosis. For localized tumors, the Gleason score helps predict the likelihood of capsule invasion, seminal vesicle invasion, or lymph node spread. Gleason score, clinical stage, and PSA together (using tables or nomograms) predict pathological stage and prognosis better than any one of them alone.

Acid phosphatase and PSA concentrations decrease after treatment and increase with relapse, but PSA is the most sensitive marker of disease progression and response to treatment.

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Treatment prostate cancer (prostate cancer)

Treatment is determined by the PSA concentration, tumor differentiation and extent, patient age, comorbidities, and life expectancy.

Most patients, regardless of age, prefer curative treatment. However, observation may be appropriate for asymptomatic patients over 70 years of age with localized prostate cancer, particularly if it is well or moderately differentiated, small in volume, or has severe comorbidities. These patients have a higher risk of dying from other causes than from prostate cancer. This approach requires periodic digital rectal examination, PSA measurement, and symptom monitoring. If symptoms worsen, treatment is necessary. In older men, observation results in the same overall survival as prostatectomy; however, patients treated with surgery have a significantly lower risk of distant metastases and disease-related mortality.

Radical prostatectomy (removal of the prostate with adnexal structures and regional lymph nodes) is probably best for patients under 70 years of age if the tumor is limited to the prostate. Prostatectomy is also appropriate for some older patients, taking into account life expectancy, comorbidities, and anesthetic and surgical risks. Complications include urinary incontinence (approximately 5-10%), bladder neck sclerosis or urethral stricture (approximately 7-20%), erectile dysfunction (approximately 30-100%, varies greatly with age and current function), and fecal incontinence (12%). Serious complications occur in more than 25% of cases, more often in older patients. Plexus-sparing radical prostatectomy reduces the incidence of erectile dysfunction but is not always feasible, depending on tumor stage and location.

Cryosurgery (destruction of prostate cancer cells by freezing with cryoprobes and then thawing) has been less studied; long-term outcomes are unknown. Adverse effects include bladder obstruction, urinary incontinence, erectile dysfunction, and rectal pain or damage.

Outcomes from radiotherapy and prostatectomy may be comparable, especially for patients with low pretreatment PSA concentrations. Standard external beam radiotherapy typically delivers 70 Gy over 7 weeks. Conformal 3-D or intensity-modulated radiation therapy safely delivers doses approaching 80 Gy to the prostate. Data suggest that the likelihood of local effects is higher, especially in high-risk patients. For most patients, some decrease in erectile function occurs in at least 40% of cases. Other adverse effects include radiation proctitis, cystitis, diarrhea, fatigue, and possibly urethral stricture, especially in patients with a history of transurethral resection of the prostate.

Whether brachytherapy (implantation of radioactive sources) can produce equivalent results is unknown. Results appear to be comparable for patients with low PSA values and well-differentiated localized tumors. Brachytherapy also reduces erectile function, although this effect may be delayed. In addition, patients may be more sensitive to phosphodiesterase-5 (PDE5) inhibitors than after resection or injury to neurovascular bundles during surgery. Increased urinary frequency, urgency, and, less commonly, retention are common but usually improve with time. Other adverse effects include increased peristalsis; urgency to defecate, rectal bleeding or ulceration, and prostate-rectal fistulas.

For larger and less differentiated tumors, especially those with a Gleason score of 8-10 and PSA >10 ng/mL, pelvic lymph nodes should be evaluated. Investigation usually involves CT or MRI, and suspicious lymph nodes can be further evaluated by needle biopsy. If pelvic metastases are detected preoperatively, radical prostatectomy is usually not performed.

For short-term palliation, one or more agents may be used, including antiandrogens, chemotherapeutic agents (eg, mitoxantrone, estramustine, taxanes), glucocorticoids, and ketoconazole; docetaxel with prednisolone is a common combination. Local radiation therapy is a common palliative treatment for patients with bone metastases.

For patients with locally advanced cancer or metastases, castration may be effective - either surgically by bilateral orchiectomy or medically with luteinizing hormone-releasing factor (LHRF) agonists such as leuprolide, goserelin, and buserelin, with or without radiation therapy.

The decrease in plasma testosterone levels with LHRH agonists is similar to that seen with bilateral orchiectomy. All of these therapies cause loss of libido and erectile dysfunction and may cause hot flashes. LHRH agonists may temporarily increase PSA levels. Some patients benefit from the addition of antiandrogens (eg, flutamide, bicalutamide, nilutamide, cyproterone) to achieve complete androgen blockade. Maximal androgen blockade is usually achieved by combining luteinizing hormone–releasing hormone agonists with antiandrogens, but the effect is only slightly greater than that of LHRH agonists (or orchiectomy) alone. Another approach is intermittent androgen blockade, which delays the onset of androgen-independent prostate cancer. Complete androgen deprivation is continued until PSA levels decline (usually to undetectable levels) and then discontinued. Treatment is restarted when PSA levels rise. Optimal treatment regimens and intervals between treatment courses have not been defined and vary widely in practice. Androgen deprivation can significantly worsen quality of life (e.g., patients' self-esteem, self-image, attitudes toward cancer and its treatment) and cause osteoporosis, anemia, and muscle loss with long-term therapy. Exogenous estrogens are rarely used because they increase the risk of cardiovascular and thromboembolic complications. There is no standard therapy for hormone-resistant prostate cancer.

Cytotoxic and biological agents (such as genetically engineered vaccines, antisense therapy, monoclonal antibodies), angiogenesis inhibitors (eg, thalidomide, endostatin) and matrix metalloproteinase inhibitors are being studied and may provide palliation and prolong survival, but their superiority over glucocorticoids has not been proven.

For low-grade tumors that extend beyond the gland capsule, there are several treatment protocols. Chemotherapy with or without hormonal therapy is used before surgery in some protocols and along with radiation therapy in others. Chemotherapy regimens vary by center and protocol.

Forecast

The prognosis for most patients with prostate cancer, particularly when the disease is localized or advanced, is favorable. The prognosis for older patients with prostate cancer differs from that for age-matched patients without prostate cancer. Long-term local control of progression and even cure are possible for many patients. The likelihood of cure, even when the cancer is localized, depends on tumor differentiation and stage. Without early treatment, patients with poorly differentiated cancer have a poor prognosis. Undifferentiated prostate cancer, squamous cell carcinoma, and ductal transitional cell carcinoma respond poorly to conventional control measures. Metastatic cancer is incurable; average survival is 1–3 years, although some patients survive for many years.

Prostate cancer: the prognosis of the disease is usually favorable, provided that prostate cancer is detected early and surgery is performed in a timely manner.

The prognosis for prostate cancer at stages I and II is that the 5-year survival rate of a patient after radical prostatectomy is 74–85%, and the 10-year survival rate is 55–56%.

The prognosis for prostate cancer with the use of radiation therapy is a 5-year survival rate of 72-80% of patients, and a 10-year survival rate of 48%. Unfortunately, prostate cancer is often detected at late stages (stages III-IV), which makes the prognosis unfavorable due to the occurrence of multiple metastatic foci in other organs of the body (5-year survival for prostate cancer at stage III is 50%, at stage IV - 20%).

The prognosis of prostate cancer is also influenced by the man's age, the presence of concomitant diseases, the level of PSA ploidy of prostate cancer cells in the blood serum, the adequacy of treatment measures and the quality of patient monitoring.

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