Diagnostics of the stages of the course of prostate cancer

Clinically distinguish localized T _1-2, N ₀, M ₀ ), topically distributed (T _3-4, N _0-1, M ₀ ) and generalized cancer (T _1-4, N _0-1, M ₁ ).

Patients with clinically localized and locally advanced stages are distributed according to the degree of risk (D'Amiko A V. Et al., 2003):

• low: stage T _1a-c; PSA level less than 10 mg / ml: Gleason grading - 2-5; with biopsy - one-sided lesion of less than 50%:
• moderate: stage T _2a; PSA level is less than 10 ng / ml; Gleason graduation - 3 + 4 = 7; with biopsy - bilateral defeat less than 50%; 
• high stage T _2b, T _3a-b; PSA level is 10-20 ng / ml; graduation by Gleason - more than 4 + 3 - 7; at a biopsy - a lesion more than 50%, a perineural invasion; 
• very high: stage T ₄; PSA level more than 20 ng / ml; graduation by Gleason - more than 8; at a biopsy - a lymphovascular invasion.

After clarifying the diagnosis and establishing the prevalence of the process (localized, locally advanced or generalized), the doctor and patient face a choice of treatment. In modern society, great importance is attached to the quality of life of patients after the start of treatment. The quality of life without treatment corresponds to the course of the underlying disease and depends on the progression of the oncological process. The change in the quality of life occurs mainly after the start of treatment and the application of one of the therapeutic or surgical methods. The precise establishment of the process stage allows not only to choose the optimal method of treatment, but also to predict the further course of the disease.

The determination of the PSA level in combination with the clinical picture of prostate cancer and the gradation of the Gleason tumor significantly increases the informative value of each of these indicators in establishing the pathological stage of cancer. A.V. Partin et al. (1997) proposed prognostic tables to predict the further spread of the tumor, the choice of treatment, the degree of radicality and the prognosis of the effectiveness of treatment

To assess the prevalence of the tumor, the most frequently used PR, TRUS, the determination of PSA level and osteoscintigraphy. If necessary, computer tomography (CT) or magnetic resonance imaging (MPT) and chest x-ray are prescribed.

Any of the imaging techniques is designed to determine the stage and evaluate the effectiveness of treatment. After verifying the diagnosis, the urologist should specify the volume of the primary tumor, its boundaries, the invasive or metastatic potential of the tumor. All these indicators are of great importance for predicting the disease and choosing a method of treatment.

[1], [2], [3], [4], [5]

Primary tumor (T)

First of all, you should determine whether the tumor is bound to the prostate gland (T _1-2 ) or out of the capsule (T _3-4 ). Finger research often does not allow to estimate a prevalence of a tumor. According to some data, the results of PRE correspond to those for histological examination in less than 50% of patients. Nevertheless, a more detailed examination is shown only when deciding on the issue of radical treatment.

The level of PSA may reflect the prevalence of the tumor, but it does not allow a precise definition of the morphological stage. The combination of PSA level, Gleason index and palpation data makes it possible to better predict the morphological stage than each of these parameters individually. The value of free PSA is debatable: in one study, the determination of free PSA content helped to clarify the stage with localized tumors, but other studies did not confirm this. Only in-depth studies will help resolve this issue.

To study the condition of the prostate gland, transrectal ultrasound is most often used. This method can detect only 60% of tumors and does not always show the germination of the capsule. Almost 60% of patients with stage T ₃. Ultrasound indicates a less common process. Ultrasonic signs of capsule germination are convexity, unevenness and rupture of the gland contour. The invasion of tumor cells into seminal vesicles is a poor prognostic sign, but information about it is extremely important for choosing a method of treatment. When TRUSI should pay attention to the echostructure of the bubbles (hyperechoic), their asymmetry, deformation and expansion. Also, the damage of seminal vesicles is indicated by the loss of roundness and compaction at the base of the gland. These signs are rather subjective, therefore it is inadvisable to rely entirely on these ultrasound data. The invasion of seminal vesicles indicates a high risk of local recurrence and metastases and a biopsy is indicated for clarification (before operations). It is not necessary to start the examination with this procedure, but if the risk of invasion is great and the choice of treatment depends on the result of the biopsy, then its implementation is justified. A negative result does not exclude microscopic invasion. Typically, seminal vesicle biopsies are carried out at the clinical stage T _2b, and above, and the PSA content is more than 10 ng / ml. The result is considered positive if at least one biopsy specimen from the base of the prostate gland contains tumor cells. To increase the accuracy of the clinical definition of the stage, not only additional studies, but also a thorough analysis of the results of the primary biopsy allow (the role and quantity of tumor foci, invasion of the capsule play a role). The degree of differentiation also has significance: at a Gleason index less than 6, the tumor is localized in 70% of cases.

Blood flow in the prostate gland with cancer is higher than in normal gland or with its hyperplasia. After castration, the intensity of blood flow in the gland is reduced. The development of echodopplerographic maps for the diagnosis and monitoring of PCa is promising, but at present there is no reliable data on the use of echodopplerography in determining the stage of the local process. It is possible to use this method to obtain additional material for targeted biopsy from the foci of pathological vascularization.

The results of visualization of prostate cancer directly depend on the technical equipment of the clinic and the experience of a specialist. That is why all modern methods of visualization are not a determining but specifying role, and the choice of a method of treatment is based on the aggregate of clinical examination data and instrumental studies.

The best opportunities for visualizing the structure of the prostate gland is MRI. The modern standard of examination of pelvic organs using the MPT method is the use of the endorectal sensor, which makes it possible to obtain an image with the maximum possible spatial resolution of 0.5-1 mm. The injection of air into the endorectal sensor provides a clear visualization of the capsule of the prostate gland, rectoprostatic angles and the recto-static fascia of Denonville. The use of the endorectal sensor in MPT does not limit the visualization of regional lymph nodes (up to the level of bifurcation of the abdominal aorta). Prostate cancer is characterized by a low signal intensity on T-weighted images against the background of a high-intensity signal from the unchanged peripheral zone of the gland. Incorrect shape, diffuse spread with mass effect, fuzzy and uneven contours - morphological characteristics of low intensity signal centers in the peripheral zone of the prostate gland, suggesting the neoplastic nature of the lesion. When dynamic contrasting, cancer sites rapidly accumulate the contrast agent in the arterial phase and rapidly remove the drug, which reflects the degree of angiogenesis and, accordingly, the degree of malignancy of the tumor. Low signal intensity is also characteristic of postbiopsy hemorrhages, prostatitis, benign prostatic hyperplasia of the neutral zone of the gland, fibrous-cicatricial changes, fibromuscular hyperplasia, consequences of hormonal or radiotherapy. MRI without dynamic contrasting does not allow to reliably differentiate most of the listed changes and diseases.

As noted above, one of the main tasks of any method of visualization in prostate cancer is the determination of the extent of the lesion of the gland and the spread of the tumor beyond the capsule. Determining tumor volume is important in terms of prognosis. The volume of the tumor less than 4 cm ³ indicates distant metastases, and 12 cm ³ - about the extremely high probability of metastases. According to studies, the accuracy of MRI in detecting foci of neoplastic lesion of the prostate is 50 to 90%. The sensitivity of MRI in determining the location of PCa is about 70-80%, while microscopic foci of cancer (foci) with MRI can not be detected.

The most important advantage of endorectal MPT is the ability to determine the localization of neoplastic lesions in areas not available to other diagnostic methods and to clarify the nature and direction of tumor growth. Thus, for example, MRI can detect foci of neoplastic lesions in the anterior sections of the peripheral zone of the prostate gland that are inaccessible to transrectal biopsy. In general, MRI significantly complements the PRI and TRUS data on tumor localization.

Endorectal MPT allows visualization of the glandular capsule, vascular bundles, seminal vesicles, glandular tip, periprostatic venous plexus and to determine the local prevalence of the gland tumor. It should be emphasized that penetration of the capsule is considered a microscopic sign, and even modern MRI devices (endorectal coil) are not able to give such information. It is only possible to obtain data on germination beyond the capsule of the gland.

Criteria for diagnosis of extracapsular extensities with MRI:

• the presence of the actual extracapsular tumor;
• unevenness of the contour of the gland (deformation, angularity);
• asymmetry of neurovascular bundles;
• obliteration of rectoprostatic angles;
• wide contact of the tumor with the capsule.

The highest specificity (up to 95-98%) and the accuracy of the MRI result is achieved when examining patients of medium or high risk of extracapsular invasion. It is believed that extracapsular invasion (according to MRI) indicates the inexpediency of surgical treatment and an unfavorable prognosis of the disease. Hormonal or radiotherapy does not affect the accuracy of detection of extracapsular proliferation of the prostate tumor. The main difficulty in detecting foci of cancer and extracapsular tumor spread is a high variability in the interpretation of tomograms by different specialists. The paramount task of a specialist in radiation diagnostics is to achieve high diagnostic specificity (even to the detriment of sensitivity) in order not to deprive operable patients of the chance of radical treatment.

The similarity of the density of cancer, hyperplasia and normal prostate tissue in CT makes this method of little use for assessing the local prevalence of the tumor. Germination in seminal vesicles is more important than sprouting into capsules, but in this case, CT also gives information only when the process is started. However, this method is actively used for marking the area of influence before radiation therapy.

The slow development of radiation diagnosis in our country led to late diagnosis of PCa and, consequently, to the insufficient prevalence of radical methods of treatment of prostate cancer (for example, prostatectomy), the low availability of modern tomographs and the lack of appropriate training programs for specialists in radiation diagnostics and urologists. Despite the fact that CT and MRI are now widespread, the level of equipping the offices and the formation of specialists in radiation diagnostics is not enough to ensure that the information obtained becomes decisive when choosing a method for treating patients with PCa.

Regional lymph nodes (N)

Evaluation of regional lymph nodes should only be in cases where it directly affects the therapeutic tactics (usually when planning radical treatment). A high level of PSA, T _2c-T3a tumors , low differentiation and perineural invasion are associated with a high risk of metastasis to the lymph nodes. Assessment of the state of lymph nodes according to the level of PSA is considered insufficient.

The necessary information is provided only by lymphadenectomy (open or laparoscopic). Recent studies of enlarged lymphadenectomy have shown that prostate cancer does not always affect the lymph nodes. With asymptomatic tumors and PSA level less than 20 kg / ml. CT scan confirms lymph node enlargement in only 1% of cases. The use of MRI or CT is justified at a high risk of metastasis, since the specificity of these methods reaches 93-96%. However, even a positive result in their use can be false, and only puncture of a suspicious lymph node allows to refuse lymphadenectomy. According to the retrospective analysis, the size of the lymph node does not always indicate the presence of metastases in it, the asymmetry of the affected lymph nodes is more informative. Currently, only 2-3% of patients who undergo radical prostatectomy for local PCa are diagnosed with lymph node metastases on the basis of post-operative histological examination.

It is recommended to use positron emission tomography (PET) and scintigraphy with labeled antibodies as methods for detecting metastasis in the lymph nodes, but their use is still limited due to insufficient sensitivity.

To assess the risk of regional lymph nodes, nomographs of Partin (2001) can be used. Nomograms - Mathematical algorithms that are used for a particular patient or for a group of patients. These tables allow to determine the probability of local spread of the tumor (per capsule, seminal vesicles) and lesions of lymph nodes based on the clinical stage, PSA level and Gleason index. In particular, they make it possible to isolate a group of patients with a low (less than 10%) probability of metastasizing to the lymph nodes (with a PSA level of more than 20 ng / _mm, stage T _1-2a and Gleason index 2-6); in this group before radical treatment, the state of the lymph nodes can not be specified. Estimation of the risk of metastasis to the lymph nodes allows the detection of tumor areas with severe anaplasia (4-5 points): if such patches are detected in four biopsies or more, or they predominate in at least one biopsy, the risk reaches 20-45%. In the remaining patients, it does not exceed 2.5%. The additional examination in such cases is not required

Remote metastases (M)

In 85% of patients dying from PCa, lesions of the axial skeleton are detected. Bone metastases arise due to the entry of cancer cells with blood flow into the bone marrow, which leads to tumor growth and lysis of bone structures. The prevalence of bone metastases affects the prognosis, and their early detection warns the doctor of possible complications. In 70% of cases metastasis is combined with an increase in the activity of bone isoenzyme alkaline phosphatase (APF). Determination of activity of alkaline phosphatase and the level of PSA in the vast majority of cases allows to detect bone metastasis. Given multivariate analysis, these indicators are affected only by the number of metastases in the bone. It is important that the activity of the bone isoenzyme of APF reflects the degree of bone damage more accurately than the level of PSA.

The most sensitive method of detecting metastases in the bone is considered scintigraphy (superior to radiography and the determination of the activity of alkaline and acid phosphatase). As a radiopharmaceutical, it is better to use technetium diphosphonates, the accumulation of which in bones is much more active than in soft tissues. A correlation is shown between a semiquantitative estimate of bone lesion and survival. Detection of distant metastases is possible in any organ. More often they arise in non-regional lymph nodes, lungs, liver, brain and skin. With appropriate complaints and symptoms for their detection, chest X-ray, ultrasound, CT and MRI are used. Tactics for suspected bone metastasis are presented in the diagram.

The most reliable laboratory indicator that helps in determining the degree of metastasis is the level of PSA. It is shown that its increase in excess of 100 ng / ml is the only parameter that reliably indicates distant metastasis. The determination of the PSA level reduces the number of patients who need bone scintigraphy. The probability of detecting metastases in the bone with a decrease in the PSA level is very low. In the absence of complaints and the initial content of PSA is less than 20 ng / ml, the detection of high and moderately differentiated tumors from scintigraphy can be discarded. At the same time, with low-grade tumors and sprouting of the capsule, scintigraphy is shown (regardless of the level of PSA).