Prostate cancer (prostate cancer) - Diagnosis

Currently, the optimal diagnostic process for early and therefore timely diagnosis of prostate cancer includes digital rectal examination, determination of the activity of serum PSA and its derivatives.

Prostate ultrasound (transrectal, transabdominal) and transrectal multifocal prostate biopsy. Accurate clinical staging is essential for choosing the optimal treatment strategy for patients with prostate cancer and helps determine its likely outcome. Diagnostic methods that help in studying the prevalence of the disease. digital rectal examination, determination of PSA levels and tumor differentiation, radiation diagnostics of prostate cancer (prostate cancer) and pelvic lymphadenectomy.

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Digital rectal examination

Digital rectal examination is a basic diagnostic technique for the initial examination of patients with prostate adenoma. Its ease of use is combined with a fairly low accuracy of staging the prevalence of the tumor process. Digital rectal examination helps to identify up to 50.0% of tumors with extracapsular growth. About half of the cases of localized prostate cancer, according to digital rectal examination, are intraoperatively staged T3 and even T4, which reduces the value of this technique. Nevertheless, the simplicity and low cost make digital rectal examination indispensable both in primary diagnostics and in subsequent staging, especially in combination with other methods. Serum prostate-specific antigen PSA is a serine protease produced almost exclusively by the prostate epithelium. The maximum normal value of PSA is 4.0 ng / ml. Recent studies indicate a fairly high frequency of detection of clinically significant cases of prostate cancer (up to 26.9%) at lower PSA values. In this regard, most foreign authors recommend performing a prostate biopsy when the PSA level increases above 2 ng/ml.

The PSA level generally reflects the prevalence and is directly related to the pathological stage and volume of the tumor. Many researchers note a clear correlation between the preoperative serum PSA levels and the frequency of extracapsular extension. It has been shown that a significant risk of extracapsular extension exists in patients with a PSA level exceeding 10.0 ng/ml. In this category of patients, the probability of extraprostatic tumor spread is approximately 2 times higher compared to those with a PSA level of less than 10.0 ng/ml. In addition, 20% of men with a PSA level of more than 20.0 ng/ml and 75% with a level of more than 50 ng/ml have lesions of the regional pelvic lymph nodes. A PSA level exceeding 50 ng/ml is associated with a high risk of a disseminated process, and more than 100 ng/ml always indicates distant metastases.

Since the PSA level depends on a number of concomitant diseases of the gland (prostatitis, adenoma) and the degree of tumor differentiation, it must be assessed in combination with other indicators.

In order to increase the specificity of this diagnostics of prostate cancer (prostate gland cancer), various PSA parameters (derivatives) are proposed, of which the following are of great clinical significance: the free and total PSA ratio (f/t-PSA), the level of annual PSA growth, the value of the PSA density of the prostate and transition zone, age norms and the period of doubling of the PSA level. Of greatest clinical significance is the determination of the coefficient of the ratio of free and bound PSA (f/t-PSA). If such a ratio does not exceed 7-10%, we are talking mainly about cancer, while when the coefficient reaches 25%, we can confidently speak of prostate adenoma. PSA density is the ratio of the serum PSA level to the prostate volume. Values of the calculated value exceeding 0.15 ng / (ml x cm ² ) indicate prostate cancer. An annual increase in the PSA level with successive measurements of more than 0.75 ng / ml also means a malignant process. However, the specificity of this indicator is quite low due to the use of test systems with different threshold sensitivity.

The use of the latest achievements in molecular biology allows us to discover and introduce new tumor markers into clinical practice that have higher sensitivity and specificity compared to PSA. Among the possible alternatives, we can highlight the determination of hepsin, NMP 48 and a number of others. One of the most promising biomarkers is considered to be PSA3 (DD3), which can be determined in urine after a digital rectal examination of the prostate. The sensitivity and specificity of this method are 74 and 91%, respectively, which is of particular importance in the group of patients with PSA below 4.0 ng/ml.

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Prostate biopsy

Prostate biopsy is an important and necessary stage in the process of prostate cancer diagnostics. It not only provides histological verification of the diagnosis, but also allows to assess the prevalence of the tumor and its size, the degree of differentiation and the nature of growth. These data have a decisive influence on determining the clinical stage of the disease and the prognosis for a particular patient, as well as on the choice of treatment method.

The currently accepted method is transrectal multifocal biopsy under ultrasound control using a special thin automatic needle. The previously widely used aspiration biopsy, which only allowed confirmation of the existence of a tumor, but did not provide reliable information about the histological structure, is used less and less.

With the introduction of serum PSA determination into clinical practice, the indications for performing biopsy have been expanded.

Standard indications:

• an increase in the PSA level above the age norm: the threshold value is considered to be 4 ng/ml. but in patients under 50 years of age this limit is reduced to 2.5 ng/ml;
• a lump detected in the prostate during a digital rectal examination;
• hypoechoic foci detected by TRUS;
• the need to clarify the stage of the disease and determine the treatment method for confirmed prostate cancer in the absence of adequate data (after TUR, open adenomectomy), as well as during observation after radiation therapy if there is a suspicion of relapse of the disease.

Contraindications for biopsy may include pronounced hemorrhoidal nodes that make it difficult to insert an ultrasound probe into the rectum, proctitis, severe general condition of the patient, exacerbation of infectious diseases, fever, and the patient taking medications that reduce blood clotting.

The main technical principle is the systematic execution of biopsy, i.e. tissue columns are taken not only from suspicious areas, but also uniformly from the entire peripheral zone. Currently, the standard is still the six-field (sextant) biopsy scheme, in which three tissue columns are taken from the peripheral zone of each prostate lobe: from the basal, middle (between the base and apex) and apical parts of the gland. The columns are obtained by the bisector of the angle between the vertical and the straight line passing along the edge of the prostate in the transverse scanning plane. Additional columns are taken from hypoechoic or palpable foci.

Currently, the technique of lateralization of injections is more promising. The column is taken along the edge of the gland contour, ensuring maximum representation of the tissue of the peripheral zone in the column. In recent years, schemes with 8, 10, 12 or more injections have become increasingly widespread, which have confirmed their advantage, especially with PSA less than 10 ng/ml and with a prostate volume of more than 50 cm ². For a gland with a volume of less than 50 cm ², a fan biopsy technique has been proposed, in which all six injections are performed in one plane passing through the apex of the gland, which ensures a more complete capture of tissue of the peripheral zone.

A biopsy from the seminal vesicles is taken if PSA levels are above 20 ng/ml, the tumor is localized in the basal parts of the gland, and there are ultrasound signs of invasion.

When evaluating the obtained biopsy material, it is necessary to take into account not only the presence of prostate adenocarcinoma, but also the extent of the lesion (one or both lobes of the gland, the number of columns with the tumor and its localization within the lobe, the frequency of detection of tumor tissue or its extent in each column), the degree of tumor differentiation according to the Gleason scale, the involvement of the gland capsule, vascular and perineural invasion (as an unfavorable prognostic sign), as well as prostatic intraepithelial neoplasia, especially high grade, which is considered a precancerous condition.

Since the absence of cancer cells in the tissue samples obtained during biopsy does not guarantee the absence of a malignant tumor, the question of the need for a repeat biopsy naturally arises. Indications for a repeat biopsy:

• high-grade prostatic intraepithelial neoplasia detected during the initial biopsy;
• a tendency towards an increase in the amount of PSA in a patient with a primary negative biopsy, an annual increase in PSA exceeding 0.75 ng/ml;
• detection of previously undetectable palpatory and/or ultrasound changes in a patient with a primary negative biopsy;
• suspicions about the non-radical nature of radiation therapy during patient observation;
• lack of sufficient information about the tumor after the initial aspiration biopsy.

The technique of repeated transrectal multifocal prostate biopsy differs from the primary biopsy by the need to take tissue columns not only from the peripheral zone of the gland, but also from the transition zone, since the probability of detecting cancer there with a primary negative biopsy from the peripheral zone increases significantly. Thus, the number of biopsies during the repeated procedure increases compared to the first biopsy. The repeated procedure is performed 3-6 months after the first.

The most common complications of transrectal prostate biopsy are macrohematuria, hemospermia, rectal bleeding, vegetative-vascular reactions. fever, acute urinary retention, damage to the bladder and urethra. There is also a risk of developing a prostate abscess, epididymitis. The spread of tumor cells along the needle into the prostate tissue has no proven clinical significance to date, as well as possible hematogenous dissemination of the tumor as a result of the biopsy.

Prostate cancer differentiation grade (prostate cancer)

The degree of adenocarcinoma differentiation also affects the frequency of extracapsular extension. The probability of detecting extracapsular extension in the surgical material with a Gleason sum of less than 7 is 3.7-16.0%, and with a sum of 7 or more, 32-56%. The accuracy of predicting extraprostatic tumor extension based on the PSA level and Gleason sum (especially in patients with PSA over 10 ng/ml and a Gleason sum of more than 7) significantly exceeds the results of MRI and is 89.7% and 63.3%, respectively.

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Radiation diagnostics of prostate cancer (prostate cancer)

TRUS, CT, MRI are used in diagnostics and preoperative staging of prostate cancer for three purposes: determining the degree of local spread of the process (hypoechoic foci, extracapsular extension and invasion into the seminal vesicles), the state of regional lymph nodes and the presence of distant metastases. Many studies have shown no difference in the accuracy of determining the degree of local spread of prostate cancer between MRI and TRUS. It has been shown that the sensitivity of TRUS in studying the presence and localization of extracapsular extension is only 66.0%, and the specificity in diagnosing prostate cancer is 46.0%.

The introduction of MRI with an endorectal coil into clinical practice has increased the sensitivity and specificity of the method in diagnosing extracapsular extension. Selection criteria for such groups:

• more than 50.0% of positive columns obtained in prostate biopsy with a PSA level of less than 4 ng/mL and a Gleason score of 7:
• PSA level 4-10 ng/ml with Gleason score 5-7:
• PSA level 10-20 ng/ml with Gleason score 2-7

The relatively low efficiency of radiation methods in diagnosing regional lymph node involvement limits their use. Most authors consider it appropriate to perform CT and MRI to determine the involvement of regional lymph nodes in patients with focal changes in digital rectal examination in the form of "cartilaginous density" nodes (high probability of extracapsular extension) and unfavorable prostate biopsy results (Gleason sum over 7, perineural invasion).

The presence and prevalence of bone metastases clearly reflect the prognosis, and their early detection warns the doctor about possible complications. The most sensitive method for detecting bone metastases is scintigraphy. In its sensitivity, it is superior to physical examination, determination of alkaline phosphatase activity in the blood serum (in 70% of cases, bone metastases are accompanied by an increase in the activity of the bone isoform of alkaline phosphatase), and radiography. The probability of detecting bone metastases with a low PSA level is low, and in the absence of complaints with a PSA of less than 20 ng / ml, highly and moderately differentiated tumors, scintigraphy can be avoided. At the same time, with low-differentiated tumors and capsule invasion, osteoscintigraphy is indicated regardless of the PSA level.

Pelvic lymphadenectomy

Pelvic lymphadenectomy (open or laparoscopic) is the "gold standard" for determining the extent of the tumor process in the regional lymph nodes due to the low sensitivity and specificity of clinical and radiological methods. Thus, according to nomograms (Partin's table), the probability of regional lymph node involvement with a Gleason sum of 8-10 is 8-34%, while histological examination of nodes removed during lymph node dissection in this group of patients showed the presence of a tumor process in 55-87%. Lymph node dissection is often performed before various methods of treating patients with prostate cancer (retropubic, perineal prostatectomy, radiation therapy). Criteria for performing pelvic laparoscopic lymphadenectomy before the final treatment option have not yet been finally determined. Most often, it is performed on patients with a Gleason sum of more than 8, a high probability of extracapsular extension, according to digital rectal examination. PSA more than 20 ng/ml or the presence of enlarged lymph nodes according to radiological diagnostics of prostate cancer (prostate cancer).

It should be noted that the predictive value of the above indicators increases with their total assessment. A major contribution in this area was made by A.V. Partin et al., who, having analyzed the results of performing RP in several thousand patients, created nomograms (Partin tables) that allow predicting the probability of localized prostate cancer, extracapsular extension, lymph node and seminal vesicle lesions in patients. These tables were developed based on a comparison of preoperative PSA values, Gleason sum, prostate biopsy data, and pathomorphological conclusions of the macropreparation after surgery.