Prostate cancer (prostate cancer)

Prostate cancer (prostate cancer) is a malignant tumor that originates from the glandular epithelium of alveolar-tubular structures predominantly in the peripheral zone of the prostate and occurs more often in older men. Prostate cancer is usually represented by adenocarcinoma. Before the obstruction of the ureters, symptoms are rare. The diagnosis is based on a digital rectal examination or determination of the PSA concentration and is confirmed by biopsy data.

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Epidemiology

Currently, prostate cancer is the most frequent oncological disease, to which numerous scientific works, periodical publications, textbooks and monographs are devoted. Nevertheless, the incidence of prostate cancer is constantly increasing, in the western industrialized countries this tumor is the second most common in men after bronchogenic carcinoma of the USA - the country where prostate adenocarcinoma is most common (with a significant prevalence of African Americans among the diseased). In these patients, prostate cancer displaces bronchial carcinoma from the first place in the scale of causes of death. The death rate 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 note its significant growth, which in the last 15 years has been almost 50%. The increase in the incidence rate can also be attributed to an increase in male life expectancy by 20 years in the past seven decades.

The lethality due to the tumor itself is currently about 30%. In Germany, prostate cancer is the third leading cause of death among men. In Austria, this disease is the most frequent malignant tumor in men and the most common cause of death from malignant diseases. In Switzerland, prostate cancer is second only to lung cancer - about 3500 new cases and about 1500 deaths due to prostate cancer are recorded annually.

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Causes of the prostate cancer (prostate cancer)

Adenocarcinoma of the prostate gland is the most common non-dermatologic cancer in men over 50 in the US. In the US, approximately 230,100 new cases and approximately 29,900 deaths (in 2004) are met every year.

The incidence rate increases with every decade of life; autopsy studies report a prevalence of prostate cancer in men in the 60-90 age group of 15-60% and an increase in its level 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. Highest risk for African Americans.

Sarcoma of the prostate gland is rarely seen, more often in children. Undifferentiated prostate cancer, squamous cell carcinoma and transitional transitional cancers are also met. Hormonal influences contribute to the development of adenocarcinoma, but not to other types of prostate cancer.

Intraepithelial neoplasia of the prostate (PID) is a precancerous histological change. It can be low or highly differentiated; highly differentiated prostate neoplasia is considered the precursor of invasive cancer.

[7], [8], [9], [10], [11]

Symptoms of the prostate cancer (prostate cancer)

Prostate cancer usually progresses slowly and rarely causes symptoms before the spread of the process. In advanced cases, there may be  hematuria  and symptoms of obstructive urination (for example, stress during urination, uncertainty, weak or intermittent urine stream, feeling of incomplete emptying, incontinence after urination). Bone pain can develop as a result of osteoblastic bone metastases (usually the pelvis, ribs, vertebral bodies).

Forms

The most widespread classification Glisson (there are five gradations, depending on the degree of loss of cell differentiation). The Glisson index is calculated by summing the two most common categories in the preparation, it has an important diagnostic and prognostic significance. Estimates of the prevalence of the tumor within the prostate and its relation to nearby organs and tissues (category T), involvement of regional tumor nodes (category N) and the presence of distant metastases (category M). In determining the degree of local spread of the process, first of all, it should be determined whether the prostate tumor is localized (localized forms of prostate cancer (T1c-T2c) or outside its capsule (T3a-T4b) .There should be regional lymph nodes only when it is directly affects the therapeutic tactics - usually when planning a radical treatment for prostate cancer (prostate cancer).

[12], [13], [14], [15]

Diagnostics of the prostate cancer (prostate cancer)

In digital rectal examination (RI), the prostate gland may be a rocky density with nodules, but the data are often normal; Seals and nodes suggest cancer, but should be differentiated from granulomatous prostatitis, prostate stones and other diseases of the prostate. The spread of seals to the seminal vesicles and the limitation of the lateral mobility of the gland suggests a localized progressive prostate cancer. Prostate cancer detected with RI, as a rule, has considerable dimensions and in more than 50% of cases it spreads beyond the borders of the capsule.

Screening for prostate cancer

Most cases are detected with screening rectal examination and determination of PSA concentration, which are usually performed annually in men over 50 years of age. Pathological findings require histological confirmation, usually by puncture biopsy with  transrectal ultrasound, which can be performed in a clinic without general anesthesia. Hypoechoic areas are most likely to represent cancer.

Although there is a trend towards a decrease in the mortality rate from prostate cancer and a decrease in the prevalence rate after the introduction of routine screening, the value of such screening has not been proven. Sometimes prostate cancer is diagnosed accidentally in a drug removed during surgery for BPH.

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

Tumors in patients with lower PSA concentrations tend to be smaller (often <1 mL) and less differentiation, although a highly differentiated cancer (Gleason 710 scale) may be present with any PSA. It is possible that 15% for PSA <4 ng / ml is a highly differentiated cancer. There are data that the PSA threshold of 4 ng / ml does not reveal some cases of cancer, its clinical significance is not clear. There is no evidence that biopsy performed in patients older than 50 years with PSA <4 ng / ml improves the result of diagnosis and treatment in patients with rapidly increasing concentrations of PSA (> 2 ng / ml per year). An inherited tumor biology can make these patients incurable regardless of early diagnosis.

Studies that determine the ratio of free PSA to total PSA are more specific than standard PSA measurements, they can reduce the frequency of biopsies in patients without cancer. Prostate cancer is associated with a lower concentration of free PSA; No diagnostic threshold has been established, but overall <1520% require a biopsy. Other isoforms of PSA and new markers for prostate cancer are still at the stage of study.

[16], [17], [18], [19]

Determination of staging and differentiation

Stratification of stages of prostate cancer is based on determining the spread of the tumor. Transrectal ultrasound can provide information for determining the stage, especially about the germination of the capsule and the invasion of seminal vesicles. The increase in the content of acidic phosphatase of blood plasma, especially in enzymatic analysis, correlates well with the presence of metastases, mainly in bones and lymph nodes. However, the enzyme content can also be increased in BPH (slightly after vigorous prostate massage), multiple myeloma, Gaucher's disease and hemolytic anemia. Radionuclide scanning of bones is performed to determine bone metastases (sometimes detect radiographically). Currently, as a tool for determining the stage and prognosis, we study diagnostics using polymerase chain reaction (PCR) based on reverse transcriptases to detect circulating prostate cancer cells.

Evaluation of differentiation, based on a comparison of the structure of the tumor with respect to the normal structure of the gland, helps determine the aggressiveness of the tumor. Evaluation takes into account the histological heterogeneity of the tumor. Gleason score is used most often: the most common structures are assigned scores from 1 to 5 and 2 points are added (total score: 2-4 = highly differentiated, 5-7 = moderately differentiated and 8-10 = undifferentiated); in another system of charging <6 points are considered highly differentiated, 7 points are moderately, and 8-10 points are considered to be low-grade. The lower the score, the less aggressive and invasive the tumor and the more favorable the prognosis. For localized tumors, the Gleason score helps predict the likelihood of invasion of the capsule, seminal vesicles or proliferation to the lymph nodes. The Gleason scale, clinical stage and PSA together (using tables or nomograms) predict the pathological stage and prognosis better than either of them individually.

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

[20], [21], [22], [23], [24], [25]

Treatment of the prostate cancer (prostate cancer)

Treatment is determined by the concentration of PSA, the differentiation and prevalence of the tumor, the age of the patient, the concomitant diseases and the expected life expectancy.

Most patients regardless of age prefer radical treatment. However, observation may be adequate for asymptomatic patients older than 70 years with localized prostate cancer, especially if it is highly or moderately differentiated, a small volume or there are concomitant severe diseases. In these patients, the risk of death from other causes is higher than that of prostate cancer. This approach requires periodic digital rectal examination, measurement of PSA concentration and symptom control. With the intensification of symptoms, treatment is necessary. In older men, observation leads to the same overall survival as prostatectomy; but patients after surgical treatment have a significantly lower risk of distant metastases and lethality associated with the disease.

Radical prostatectomy (removal of the prostate gland with subordinate structures and regional lymph nodes) is probably better for patients under 70 years of age if the tumor is confined to the prostate gland. Prostateectomy is suitable for some elderly patients, taking into account life expectancy, concomitant diseases, anesthesia and surgical risk. Complications include urinary incontinence (approximately 5-10%), bladder neck sclerosis or urethral stricture (approximately 7-20%), erectile dysfunction (approximately 30-100%, significantly depends on age and current function) and stool incontinence (12% ). Serious complications are met in more than 25% of cases, more often in old age. Radical prostatectomy with preservation of the nerve plexus reduces the likelihood of erectile dysfunction, but is not always feasible, depending on the stage of the tumor and location.

Cryodestruction (destruction of prostate cancer cells by freezing with the use of cryoprobes followed by thawing) is less well studied; distant results are unknown. Negative effects include bladder obstruction, urinary incontinence, erectile dysfunction and rectal pain or damage.

The results of radiotherapy and prostatectomy may be comparable, especially for patients with a low PSA concentration before treatment. Standard remote radiation therapy usually provides a dose of 70 Gy for 7 weeks. Conformal 3D radiation therapy or radiotherapy with modulated intensity safely provides doses approaching 80 Gy at the prostate gland. The data show that the probability of local exposure is higher, especially for patients at high risk. For most patients, a slight 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 anamnesis of transurethral resection of the prostate in the anamnesis.

Can brachytherapy (implantation of radioactive sources) lead to equivalent results, is still unknown. The results, apparently, are comparable for patients with low PSA and highly differentiated localized tumors. Brachytherapy also reduces erectile function, although this effect can be delayed. In addition, patients may be more sensitive to phosphodiesterase-5 inhibitors (PDE5) than after resection or damage to the neurovascular bundles during surgery. Increasing urination, urgency and, less often, urinary retention are common, but usually weaken over time. Other adverse effects include increased peristalsis; urgency of defecation, rectal bleeding or ulceration and prostatectal fistulas.

For large and less differentiated tumors, especially with Gleason score 8-10 and PSA> 10 ng / ml, pelvic lymph nodes should be studied. The study usually involves CT or MRI, suspicious lymph nodes can later be evaluated with a puncture biopsy. If pelvic metastases are detected before surgery, radical prostatectomy is usually not performed.

For a short-term palliative effect, one or more drugs can be used, including antiandrogens, chemotherapeutic agents (eg mitoxantrone, estramustine, taxanes), glucocorticoids and ketoconazole; Docetaxel with prednisolone is a common combination. Local radiotherapy is an ordinary palliative procedure for patients with bone metastases.

For patients with locally advanced cancer or metastases, castration may be effective - either surgical by bilateral orthochromia, or medicamentous agonists of the luteinizing hormone releasing factor (RFLH), for example leuprolide, goserelin and buserelin, with or without radiotherapy.

Reduction of testosterone in the blood plasma against the background of admission of RFLH agonists is similar to that of bilateral orchiectomy. All these types of therapy cause loss of libido and erectile dysfunction and can cause paroxysmal sensations of heat. RFLH agonists can lead to a temporary increase in the concentration of PSA. For some patients, the effective addition of antiandrogens (in particular, flutamide, bicalutamide, nilutamide, cyproterone) for complete androgen blockade. The maximum blockade of androgens is usually achieved by a combination of luteinizing rylening hormone agonists with anti-androgens, but its effect is slightly superior to that of RFLH agonists (or orchiectomy) alone. Another approach is the intermittent blockade of androgens, which implies a delay in the manifestations of androgen-independent prostate cancer. Complete deprivation of androgens is continued until the PSA concentration decreases (usually to an undetectable value), then stop. Treatment starts again when the PSA concentration rises. Optimal treatment regimens and intervals between therapy courses have not been determined, they vary widely in practice. Deprivation of androgens can significantly impair the quality of life (for example, patients' self-esteem, attitude towards themselves, cancer and its treatment) and cause osteoporosis, anemia and loss of muscle mass with prolonged therapy. Exogenous estrogens are rarely used because they increase the risk of developing cardiovascular and thromboembolic complications. There is no standard therapy for hormone-resistant prostate cancer.

Cytotoxic and biological preparations (such as genetically engineered vaccines, antisense therapy, monoclonal antibodies), angiogenesis inhibitors (in particular, thalidomide, endostatin) and matrix metalloproteinase inhibitors are being studied, they can provide palliative therapy and prolong survival, but their advantage over glucocorticoids was not proved.

For low-differentiated tumors that spread beyond the glandular capsule, there are several treatment protocols. Chemotherapy with hormonal therapy or without it is used before surgical treatment in some protocols, and along with radiotherapy - in others. The regimens of chemotherapy depend on the center and protocol.

Forecast

The prognosis for most patients with prostate cancer, especially when the process is localized or spread out, is more favorable. The prognosis for elderly patients with prostate cancer differs from that in patients of the corresponding age without prostate cancer. For many patients, prolonged local control of progression and even cure is possible. The likelihood of a cure, even when the cancer is localized, depends on the differentiation of the tumor and the stage. Without early treatment, patients with low-grade cancer have an unfavorable prognosis. Undifferentiated prostate cancer, squamous cell and transitional cell carcinoma react poorly to conventional control measures. Metastatic cancer is incurable; the average life expectancy is 1-3 years, although some patients live many years.

Prostate cancer: the prognosis of the disease is most often favorable, provided early detection of prostate cancer and timely surgery.

Prognosis of prostate cancer in the first and second stages - a 5-year survival of the patient after a radical prostatectomy surgery is 74-85%, and a 10-year-old patient - 55-56%.

Prognosis for prostate cancer in the use of radiation therapy - a 5-year survival rate of 72-80% of patients, a decade-old - 48%. Unfortunately, often prostate cancer is found in the late stages (III-IV stage), which makes the prognosis unfavorable because of the emergence of multiple metastatic foci in other organs of the body (5-year survival in prostate cancer in stage III is 50%, IV stage - 20%).

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

[26], [27], [28], [29], [30], [31]