Prostate cancer (prostate cancer): diagnosis

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

Ultrasound of the prostate (transrectal, transabdominal) and transrectal multifocal prostate biopsy. Accurate clinical staging is critical to choosing the optimal treatment strategy for prostate cancer patients and allows you to determine the likely outcome. Diagnostic methods that help in the study of the prevalence of the disease. Digital rectal examination, determination of PSA level and degree of tumor differentiation, radiation diagnosis of prostate cancer (prostate cancer) and pelvic lymphadenectomy.

[1], [2], [3], [4],

Finger rectal examination

Finger rectal examination is the basic diagnostic technique for primary examination of patients with prostate adenoma. Simplicity of its use is combined with sufficiently low accuracy of staging of the prevalence of the tumor process. Finger rectal examination helps to detect up to 50.0% of tumors with extracapsular growth. About half of the cases of localized forms of prostate cancer, according to digital rectal examination, are intraoperatively T3 and even T4, which reduces the value of this technique. Nevertheless, simplicity and low cost make digital rectal examination indispensable, both in the initial diagnosis and in the subsequent staging. Especially in combination with other methods. Serum prostate-specific antigen PSA - serine protease, which produces almost exclusively the epithelium of the prostate. The limiting normative value of PSA is 4.0 ng / ml. Recent studies indicate a sufficiently high frequency of detection of clinically significant cases of prostate cancer (up to 26.9%) with lower values of PSA. In this regard, most foreign authors recommend performing a prostate biopsy with an increase in PSA levels of more than 2 ng / ml.

The level of PSA as a whole reflects the prevalence and is directly related to the pathological stage and the volume of the tumor. Many researchers note a clear correlation of preoperative serum PSA levels with the frequency of extracapsular extensiveness. It was shown that a significant risk of extracapsular extention exists in patients with a PSA level exceeding 10.0 ng / ml. In this category of patients the probability of extraprostatic spread of the tumor is approximately 2 times higher than those with PSA 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 there is a lesion of regional pelvic lymph nodes. The PSA level exceeding 50 ng / ml is associated with a high risk of disseminated process, and more than 100 ng / ml always indicates distant metastases.

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

To increase the specificity of this prostate cancer diagnosis (prostate cancer), various PSA parameters (derivatives) are offered, of which the important free clinical and general PSA (f / t-PSA), the annual PSA growth, the PSA density prostate and transitional zones, age norms and the period of doubling the level of PSA. The greatest clinical significance is the determination of the ratio of free and bound PSA (f / t-PSA). If this ratio does not exceed 7-10%, it is mainly about cancer, while the coefficient reaches 25%, we can say with confidence about prostate adenoma. The density of PSA is the ratio of the serum PSA level to the volume of the prostate. The values of the calculated value exceeding 0.15 ng / (mlxcm ² ), testify in favor of prostate cancer. The annual increase in PSA levels in sequential 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.

Application of the latest achievements in molecular biology makes it possible to discover and introduce into clinical practice new tumor markers with higher sensitivity and specificity in comparison with PSA. Among the possible alternatives can be identified the definition of Hepsin, NMP 48 and a number of others. One of the most promising biomarkers is PSA3 (DD3), which can be determined in the urine after a digital rectal examination of the prostate. The sensitivity and specificity of this method is 74 and 91%, respectively, which is of particular importance in the PSA group below 4.0 ng / ml.

[5], [6], [7], [8], [9]

Prostate biopsy

Prostate biopsy is an important and necessary stage in the diagnosis of prostate cancer. It not only provides a 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 the definition of the clinical stage of the disease and the prognosis in a particular patient, as well as on the choice of the method of treatment.

A currently accepted technique is a transrectal multifocal biopsy under ultrasound control with a special thin automatic needle. A widely used aspiration biopsy. Allowing only to confirm the existence of a tumor, but not giving reliable information about the histological structure, are used less and less.

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

Standard readings:

• increase in the PSA level above the age limit: a threshold value of 4 ng / ml is considered. But v patients younger than 50 years, this border is reduced to 2.5 ng / ml;
• compaction, revealed in the prostate in 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), and also during follow-up after radiation therapy for suspected relapse.

Contraindications for biopsy can be expressed hemorrhoids, making it difficult to conduct an ultrasound sensor in the rectum, proctitis, severe general condition of the patient, exacerbation of infectious diseases, fever, the patient taking drugs that reduce blood clotting.

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

At present, the technique of lateralizing injections is more promising. The fence is taken along the edge of the gland contour, ensuring the maximum representation of the tissue of the peripheral zone in the column. Increasingly widespread in recent years are schemes with 8. 10. 12 injections or more, confirming 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 less than 50 cm ^2, a technique for fan biopsy was suggested, in which all six injections were performed in the same plane passing through the tip of the gland, which ensured a more complete capture of the tissue of the peripheral zone.

A biopsy of seminal vesicles is taken at a PSA value above 20 ng / ml, tumor localization in the basal parts of the gland, ultrasound signs of invasion.

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

Since the absence of cancer cell tissue samples in biopsy specimens does not guarantee the absence of a malignant tumor, the question of the need for a repeated biopsy is natural. Indications for repeated biopsy:

• Primary biopsy revealed a high degree of prostatic intraepithelial neoplasia;
• the tendency to increase the amount of PSA in a patient with a primary negative biopsy, an annual increase in PSA exceeding 0.75 ng / ml;
• detection of a patient with a primary negative biopsy of previously undetectable and / or ultrasonic changes;
• suspicions of non-radicableness of radiotherapy in the process of observing patients;
• lack of sufficient information on the tumor after a primary aspiration biopsy.

The technique of repeated transrectal multifocal biopsy of the prostate 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 transitional zone, since the probability of detecting cancer there during primary negative biopsy from the peripheral zone is significantly increased. Thus, the number of biopsies in a repeated procedure increases in comparison with the first biopsy. Repeat the procedure performed after 3-6 months after the first.

The most common complications of transrectal biopsy of the prostate are macrohematuria, hemospermia, rectal bleeding, vegetovascular reactions. Fever, acute retention of urination, damage to the bladder and urethra. There is also a possibility of developing an abscess of the prostate, epididymitis. The spread of tumor cells along the needle in the prostate tissue has not been proven to clinical significance to date, as well as the possible hematogenous dissemination of the tumor as a result of biopsy.

Degree of differentiation of prostate cancer (prostate cancer)

The degree of differentiation of adenocarcinoma also affects the frequency of extracapsular extensiveness. The probability of detection of extracapsular extension in the operating material with Gleason sum less than 7 is 3.7-16.0%, and for a total of 7 and more than 32-56%. The accuracy of the prediction of the extaprostatic spread of the tumor based on the level of PSA and the Gleason score (especially in patients with PSA more than 10 ng / ml and Gleason's sum more than 7) is significantly higher than the results of MRI and are respectively 89.7% and 63.3%.

[10], [11], [12], [13], [14], [15], [16]

Radiation diagnosis of prostate cancer (prostate cancer)

TRUS, CT, MRI are used in the diagnosis and preoperative staging of prostate cancer with three purposes: determining the degree of local spread of the process (hypoechoic foci, extracapsular extension and invasion of seminal vesicles), regional lymph node conditions and the presence of distant metastases. Many studies have shown no difference in the accuracy of determining the extent of local spread of prostate cancer between MRI and TRUS. It was shown that the sensitivity of the TRUS in the study of the presence and localization of extracapsular extensibility is only 66.0%, and the specificity in the diagnosis of prostate cancer is 46.0%.

The introduction into clinical practice of MRI with an endorectal coil made it possible to increase the sensitivity and specificity of the method in the diagnosis of extracapsular extensia. Selection criteria for such groups:

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

The rather low efficiency of radiation methods in the diagnosis of lesions of regional lymph nodes limits their use. Most authors consider it advisable to perform CT, 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 extention) and unfavorable results of prostate biopsy (Gleason sum more than 7, perineural invasion) .

The presence and prevalence of metastases in the bone clearly reflect the prognosis, and their early detection warns the doctor about possible complications. The most sensitive method in detecting bone metastases is scintigraphy. In its sensitivity, it exceeds the physical examination, the determination of the activity of alkaline phosphatase in the blood serum (in 70% of observations, bone metastases accompany an increase in the activity of the bone isoform of alkaline phosphatase), radiography. The probability of detecting metastases in the bone with a low PSA level is small, and in the absence of complaints with PSA less than 20 ng / ml, high and moderately differentiated tumors from scintigraphy can be discarded. At the same time, with low-grade tumors and sprouting of the capsule, osteoscintigraphy is shown irrespective of the level of PSA.

Pelvic lymphadenectomy

Pelvic lymphadenectomy (open or laparoscopic) is the "gold standard" for determining the prevalence of the tumor process in regional lymph nodes because of the low sensitivity and specificity of clinical and radiation methods. So, according to nomograms (Partin's tables). The probability of regional lymph node involvement with the Gleason score 8-10 is 8-34%, while the histological examination of nodes removed from lymph node dissection in this group of patients showed the presence of a tumor process in 55-87%. Lymphadenectomy is often performed before various methods of treatment of patients with prostate cancer (retropubic, perineal prostatectomy, radiation therapy). The criteria for conducting pelvic laparoscopic lymphadenectomy before the final treatment option are not finally defined. It is most often performed in patients with a Gleason score greater than 8, a high probability of extracapsular extensis, according to a digital rectal examination. PSA is more than 20 ng / ml or the presence of enlarged lymph nodes according to radiation diagnosis of prostate cancer (prostate cancer).

It should be noted that the predictive value of the above indicators increases with their total evaluation. Great contribution in this area was made by A.V. Partin and co-workers, who analyzed the results of performing RPE in several thousand patients, created nomograms (Partin tables), which allow predicting the probability of localized PCa, extracapsular extensia, lesions of lymph nodes and seminal vesicles in patients. These tables were developed on the basis of comparison of the values of preoperative PSA level, Gleason's sum, data obtained with prostate biopsy and pathomorphological conclusion of the macro preparation after the data operation.