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Classification of prostate cancer by stages


Classification Of Prostate Cancer By Stages

Prostate cancer: stages, signs, classification



Signs of prostate cancer (symptoms)


Unfortunately, but with Prostate cancer, the first signs may appear only in the later stages of the disease. However, prostate cancer (PCa) can be suspected with the following symptoms:



  • problems with urine outflow inconvenience when urinating (weakening of the jet, pain, severe retention, feeling of an incompletely emptied bladder;
  • red urine due to blood;
  • erectile dysfunction;
  • pain in the region of the pubic bone, perineum;
  • in advanced stages of prostate cancer and metastases, the signs are very extensive, and the symptoms are serious: weight loss, low hemoglobin, back pain, with compression of the spinal cord, swelling and pain of the lower extremities, up to paralysis.


RISK FACTORS


Prostate cancer is one of the most common cancers in men in Germany. According to the Robert Koch Institute, about 60,000 new cases are diagnosed each year. In part, this statistic is due to the fact that in Germany preventive diagnosis of prostate cancer is almost mandatory. Men over 40 go for diagnostics themselves, without waiting for the first signs. The average age of patients is 68 years. Until the age of 40, the disease practically does not occur.


A malignant tumor of the prostate grows very slowly, remaining unnoticed for a long time. Only every seventh patient seeks medical help in the early stages of prostate cancer, the rest, unfortunately, are diagnosed late. Approximately every third patient already has metastases at the time of diagnosis, comments Prof. Dr. Stefan Müller, Chief Physician of the Clinic for Urology at the University of Bonn, Germany.


A study conducted in Heidelberg in 2010 showed that the risk of the disease is much higher in men whose relative has a history of prostate cancer. For example, in men aged 65-74 years, the risk increases by 1.8 times if the father has the disease. Today, no one doubts the increased risk of prostate cancer due to heredity.


The causes of prostate cancer are still not clear enough: in addition to hereditary factors, an increased fat content and a lack of vegetable fiber in the diet are being actively discussed. It is assumed that vitamin E, unsaturated fatty acids, selenium, and soy products contribute to the prevention of the disease.


So, the following factors are of great importance in the occurrence of prostate cancer:


Unlike benign prostatic hyperplasia (prostate adenoma), when the signs are quite pronounced, prostate cancer malignant neoplasms arise from the outer zone of the prostate and grow very slowly, without causing any complaints. In the advanced stages of prostate cancer, pain when urinating, frequent urination, and difficulty urinating may occur.



CLASSIFICATION OF PROSTATE CANCER clinical stages


A more extensive system is the TNM classification, where



  • T - characteristic of the tumor itself from English. -tumor- - "tumor",
  • N - damage to regional and distant lymph nodes from English. -node- - "node" and
  • M - prevalence of metastases from English. -metastase- - "metastasis".

Table 1. TNM classification. Source: German Society for Oncology.


Classification of prostate cancer according to the Gleason scale allows for a prognostic assessment of the course of the disease and is based on the degree of tumor differentiation. In general, the lower the Gleason score, the better the prognosis. The maximum score is 10 points.



Diagnostic methods


As a marker for the diagnosis of prostate cancer in Germany, the prostate specific antigen PSA (PSA) is used, the level of which is partly dependent on age, and is usually no more than 2.5-4 ng / ml in the blood serum of men.. This is a simple a diagnostic method that every man can decide on, without waiting for signs of prostate cancer. Cycling, rectal exams, and sex increase this indicator to some extent. Therefore, at elevated values, a second control after a few weeks is necessary. On the other hand, a normal PSA value does not rule out prostate cancer.


In addition to PSA, another prostate marker is known - prostatic acid phosphatase, PCF (PAP). Prior to the widespread introduction of PSA, this marker was used in the early diagnosis of prostate cancer. Today, it is usually analyzed before starting treatment to predict the likelihood of re-elevation of PSA levels after local therapy - radical prostatectomy, brachytherapy, or external radiation.Elevated levels of PCF (above 3 ng/ml) may indicate an aggressive form of cancer and a tumor that extends beyond the border of the organ. After therapy, PCF analysis may indicate the onset of the metastasis process. This marker can increase during manipulations on the gland, so rectal examination is not recommended 48 hours before determining the level of the marker.


If a man already has signs of the disease, an ultrasound method is also mandatory to diagnose prostate cancer, often followed by a prostate biopsy. Under local anesthesia with a fine needle, punctures are made and at least three samples are taken from each half of the gland. Tumors larger than 10 mm can be detected with sufficient reliability using ultrasound, less than 10 mm - only in 20% of cases.


According to the results of the biopsy, the so-called histological division is performed depending on the initial type and stage of maturity of the cells. About 95% of prostate cancer cases are of the prostate adenocarcinoma type.



Stages of prostate cancer according to clinical and pathological classification


There are 4 stages of prostate cancer according to the clinical and pathological classification. The grading system for prostate cancer may number stages from 1 to 4, or the letters A, B, C, or D (Jew-Whitemore). Unlike the digital system of stages, the Jewet-Whitemore classification has several more sublevels:



  • Stage A (A1, A2): early stage, in which cancer cells are found only in the prostate gland, but have no symptoms, are rarely diagnosed,
  • Stage B (B0, B1, B2): cancer cells are still within the prostate, but the tumor is growing and is already palpable, the PSA level is elevated,
  • Stage C (C1, C2): cancerous tumor cells are found already behind the prostate, i.e. grew beyond the capsule of the gland and grew into neighboring organs,
  • Stage D (D0, D1, D2, D3): the most severe stage of PCa: the tumor metastasizes to distant parts of the body, affecting organs and lymph nodes.

If the patient's condition is assessed using studies of the volume of the smallest tumor (C1-C3), then they say that the clinical classification of prostate cancer is cTNM ("c" clinical). Such a classification is determined before the upcoming treatment and is called pre-therapeutic. The classification, which takes into account the results of prostate cancer surgery and the study of biopsy material (C4 C5), is defined as pTNM (where "p" is pathological) postoperative, histopathological classification.


For example: the formula pT1, pN0, M0 characterizes a small initial tumor of the prostate without lesions of the lymph nodes and without the presence of metastases; histopathology was performed on the original tumor and nearby lymph nodes, but distant metastases were only looked for clinically.


The first to try to repel the attack are the lymph nodes - guardians of agents alien to the body. Stage C prostate cancer affects the lymph nodes in the groin and pelvis. Metastasizes prostate cancer more often in the pelvis and lumbar spine (Stage D). This causes pain, and sometimes even pathological fractures.



ARSENAL AGAINST PROSTATE CANCER AT DIFFERENT STAGES


All methods of prostate cancer classification are designed to better understand the necessary treatment methods for a particular patient. The treatment of prostate cancer in Germany is carried out according to the principle: "extensively, as much as necessary, and sparingly, as far as possible." Treatment methods are selected individually and depend on the patient's age, concomitant diseases, stage of prostate cancer.


In the early stages of PCa, a complete cure is possible. The most commonly performed operation is radical laparoscopic prostatectomy. A recent Swedish study concluded that in men younger than 65 years of age in the early stages of the disease, the chances of survival increase with emergency surgery.


A possible complication of surgical treatment - urinary incontinence - in Germany 6 months after surgery is observed only in a small number of patients. In more than 50% of patients, potency is restored after surgery, and in 95% the ability to retain urine. "The experience and skills of the surgeon are decisive," says Prof. Jurgen Gschwend, Chief Physician of the Urology Clinic and Polyclinic of the Technical University of Munich.


To date, it is possible to perform the operation not only by laparoscopic (minimally invasive) access, but also by the use of robotics. With the help of a special da Vinci robot, the finest movements are made, possible trembling of the surgeon's hands is leveled, and clear three-dimensional images of the surgical field are obtained.


An alternative method is radiation therapy. Conventional radiation therapy is performed 5-7 times a week for eight weeks. The duration of each such procedure is about 15 minutes.In many centers, radiation therapy is also prescribed after surgery if the tumor was not completely removed during the procedure.


Radioactive implants have also been developed, which are inserted into the prostate gland and irradiate the surrounding tissues for about one year (brachytherapy).


One of the most common indications for radiotherapy for prostate cancer in Germany is bone metastases; such treatment helps to limit them and reduce pain.


In the advanced stages of PCa, hormonal treatment is used, which can be divided into two groups: ablative, or suppressive treatment, and additional treatment. Suppressive treatment is similar to medical castration: the effect of testosterone on the body is completely suppressed. In this case, there are multiple side effects: impotence, decreased libido, an increase in the size of the mammary glands (gynecomastia), weight gain, osteoporosis is possible. With suppressive hormone therapy, gonadotropin-releasing hormone antagonists are prescribed, blocking the secretion of the hypothalamic hormone.


Another group of drugs prescribed for hormone therapy are antiandrogens. They do not reduce the secretion of testosterone, but protect the prostate gland from the stimulating effect of this hormone. Since the level of testosterone in the blood does not change, there are significantly fewer side effects with this treatment. Estrogens reduce testosterone levels within one week, but differ in multiple side effects on the male body. Despite the fact that estrogen treatment is cheaper, it is rarely recommended.


At stage 4, with metastases of prostate cancer, chemotherapy is especially indicated. In any case, chemotherapy is selected individually depending on the effectiveness and tolerability of the drugs.


We will tell you more about prostate cancer treatment methods on the following pages.



Classification of prostate cancer


The article presents international classifications of prostate cancer, which are used by urologists and oncologists around the world. These are the international TNM system, the Gleason scale and the Jewet-Whitemore system, as well as prognostic risk factors according to DAmico and Partin tables.



TNM classification of prostate cancer


The classification of the stages of cancer development was developed by P. Denoix (France) in the period from 1943 to 1952, then it underwent a number of changes, and in 2002 an international decision was made to stop making changes until there were radical changes in diagnosis and treatment of malignant tumors. The latest classification of the TNM system has been supported by all national TNM committees and is used throughout the world, as it helps in research and interpretation of the results, as well as in the development of treatment algorithms. The TNM system is used in the diagnosis and staging of prostate cancer.



T primary tumor


TX is not enough data to assess the primary tumor.


T0 primary tumor is not detected.


T1 tumor is not clinically manifested, is not palpable and is not visualized by special methods.


- T1a tumor is incidentally detected during histological examination and makes up less than 5% of the resected tissue.


- T1b tumor is incidentally detected during histological examination and makes up more than 5% of the resected tissue.


- T1c tumor is diagnosed with a needle biopsy of the prostate (due to high PSA levels).


T2 tumor limited to the prostate or extending into the capsule.


- T2a tumor affects half of one lobe or less.


- T2b tumor affects more than half of one lobe, but not both lobes.


- T2c tumor affects both lobes.


T3 tumor extends beyond the prostate capsule.


- T3a tumor extends beyond the capsule (unilateral or bilateral).


- T3b tumor extends to the seminal vesicle.


T4 non-displaceable tumor or tumor that has spread to adjacent tissues and organs other than the seminal vesicles: bladder neck, external sphincter, rectum, levator ani, and/or pelvic wall.



N regional lymph nodes.


In relation to the prostate gland, regional lymph nodes are the nodes of the small pelvis, which are located below the bifurcation of the common iliac arteries. Category N does not depend on the side of localization of regional metastases.


NX insufficient data to evaluate regional lymph nodes.


N0 no metastases in regional lymph nodes.


N1 has metastases in regional lymph nodes.



M distant metastases.


МX it is not possible to determine the presence of distant metastases.


M0 signs of distant metastases are absent.


M1 has distant metastases.


- M1a involvement of non-regional lymph nodes.


- M1b bone lesion is present.


- M1c there are other localizations of distant metastases (lung, liver, etc.).



Gleason score for prostate cancer


The Gleason score calculates the grade of tumor found in a prostate biopsy. The higher the Gleason score, the more aggressive the tumor. When evaluating a tumor on the Gleason scale, the difference between cancer cells that were obtained during a prostate biopsy and normal prostate cells is taken into account. If cancer cells do not differ from normal cells, then on the Gleason scale, the tumor receives 1 point. Otherwise, with a complete difference, the tumor is scored a maximum score of 5.


The Gleason score is the sum of the Gleason scores (from 1 to 5 points) for the 2 largest or most malignant tumors found in the tissues of the prostate.



Gleason sum estimate


- low-grade Gleason score (less malignant tumors) with a Gleason score of 6 points.


- intermediate Gleason score (medium-malignant tumors) with a Gleason score of 7 points.


- high-grade Gleason score (highly malignant tumors) with a Gleason score of 8 to a maximum of 10 points.


For example, let's take the Gleason sum, which is equal to 5 points, this will mean that the 2 largest or malignant tumors have 2 and 3 points each. That is, these are less malignant tumors.



Jew-Whitemore classification of prostate cancer


According to the Jewet-Whitemore system, the classification of prostate cancer is divided into stages A, B, C and D. Stages A and B are considered curable, and stages C and D are also treated, but their prognosis is more unfavorable.


This is the earliest stage. There are no symptoms. Cancer cells are located in the prostate.


A1 cancer cells are well differentiated, their moderate anomaly is noted.


A2 moderately or poorly differentiated cancer cells at multiple locations in the prostate.


The tumor does not extend beyond the prostate. It is felt during palpation and / or an elevated PSA level is determined.


B0 tumor within the prostate, not palpable; PSA level is elevated.


B1 single tumor node in one lobe of the prostate.


B2 extensive tumor growth in one or both lobes of the prostate.


The tumor extends beyond the prostate capsule and spreads to neighboring tissues and organs, including the seminal vesicles.


C1 tumor grows beyond the prostate capsule.


C2 tumor overlaps the lumen of the urethra or bladder.


The tumor metastasizes to regional lymph nodes or to distant organs and tissues (lungs, liver, bones, stomach, etc.).


D0 is a clinically detectable metastasis with elevated PSA levels.


D1 regional lymph nodes are affected.


D2 affects distant lymph nodes, organs and tissues.


D3 metastases after treatment.



DAmico classification of predictive risk factors


This classification looks at the likelihood of cancer progression in the initial stages to clinical symptoms and / or death, as well as the risk of recurrence after local cancer treatment. According to the Damiko prostate cancer classification, patients are assigned to one of the disease progression groups: low, moderate, or high. The following indicators are taken for evaluation:


Classification of cancer according to the TNM system, namely the T indicator, the prevalence of the primary tumor;


Gleason score for prostate cancer


Blood level of prostate-specific antigen (PSA).


The low-risk group includes patients who:


PSA level 10 ng/ml, Gleason score 6 points, clinical stage T1-2a.


The intermediate risk group includes patients who:


PSA level 10-20 ng/ml, Gleason score - 7 points, Clinical stage T2b.


The high-risk group includes patients who:


PSA level >20 ng/ml, Gleason score 8 points, Clinical stage T2c-3a.



Alan Partin's tables or nomograms


Partin's graph is a scale that takes into account mathematical models calculated on the basis of the PSA level, Gleason scores and the clinical stage of prostate cancer according to the TNM classification, namely the T-value of the primary tumor. Partin's graph allows predicting the further progression of the disease. Nomograms were compiled based on a study of data on men who were treated for prostate cancer. Based on these data, tables were compiled that are divided:


Prostate cancer grade from T1c to T2c.


According to the level of PSA in the blood, the following categories are distinguished from 0 to 10 ng / ml, and more than 10.0 ng / ml.


Gleason scores are divided into 3 categories from 2 to 4, 5 to 6, or 8 to 10.


This is how Partin's modified nomograms look like, which can be used to determine the likelihood of further progression of prostate cancer.



Partin Tables


Let's take a closer look at how to use Partin tables. For example, a patient has a PSA level of 3.1 ng / ml, a Gleason score of 3 + 47, clinical stage T2a (the tumor is palpable and affects less than half of one lobe). In the second table, in the PSA value, we are looking for a range from 2.6-4.0 ng / ml, Gleason scores 3 + 47. We look at the intersection and on 4 lines we look at the percentage of progression: the probability of developing a tumor limited to the boundaries of the prostate gland is 50% (from 43 to 57%), growth beyond the prostate is 41% (from 35 to 48%), seminal vesicle damage is 7% (from 3 to 12%), spread to the lymph nodes 2% (from 0 to 4%).


To facilitate obtaining data from Partin's tables, there are computer programs where you only need to enter the initial data.


In addition to the Partin tables, there are Kattan nomograms that allow you to predict the results of prostate cancer treatment and make a prognosis for life expectancy.


Using a classification to indicate the stages of prostate cancer helps oncologists determine the treatment tactics (a combination of methods or monotherapy: hormone therapy for prostate cancer, chemotherapy, radiation therapy, surgery), make a prognosis for the progression of the disease and the patient's life expectancy. In addition, a single classification helps to process the findings from different studies, which in turn leads to the accumulation of experience and the improvement of existing methods for the treatment and diagnosis of prostate cancer.



International classification of stages of development of prostate cancer according to the TNM system: interpretation of values and prognosis


For the successful treatment of any oncological disease, it is necessary to correctly establish the stage of the development of the disease.


The degree of the disease depends on how large the tumor is, whether it is aggressive, or whether other organs are affected.


In order to diagnose and describe a tumor in the prostate, urologists use several tools, but the TNM classification of prostate cancer is mandatory. This system classifies the size and metastasis of the tumor.


The aggressiveness of cancer is determined by the Glisson scale. Predictions for the development and treatment of the disease can be calculated using special tools - mathematical models.



Classification of prostate cancer according to the TNM system (TNM)


The TNM system (TNM) is an international classification of the stages of development of malignant neoplasms. It was developed in 1943-1952 by the French scientist Pierre Denois. Now recognized worldwide and recommended for use by the International Cancer Union.


Prostate cancer stages


The system got its name from the first letters of the Latin words tumor (tumor), nodus (node) and the Greek letstasir (movement).


It describes the tumor in three main parameters: the size of the neoplasm (including whether the tumor has "come out" of the prostate or not yet), the presence of metastases in nearby (regional) lymph nodes for the tumor, and the process of metastasis to other organs.


Category T


The abbreviation T describes the presence and size of a neoplasm in the prostate.


The following conventions are used to describe the spread of cancer:



  • TX - cannot be estimated due to lack of necessary data;
  • Т0 - not defined in any way;
  • T1 - diagnosed, but does not manifest itself clinically, is not found during rectal examination (palpation), is not visible on ultrasound. In this case, the main category is divided into clarifying subsections;
  • T1a - found by chance during the study of prostate tissue (for example, during an operation to remove an adenoma), is less than 5% of the examined tissue;
  • T1b - found by chance during the study of prostate tissue (for example, during an operation to remove an adenoma), makes up more than 5% of the examined tissue;
  • T1c - diagnosed during a biopsy (for example, due to a high level of a prostate-specific tumor marker);
  • T2 - tumor detected, limited to the capsule of the prostate gland. In turn, it is divided into clarifying subsections;
  • T2a - no more than half of one lobe of the prostate is affected;
  • T2b - more than half of one lobe of the prostate is affected, but not both;
  • T2c - both lobes of the prostate capsule are affected;
  • T3 - the tumor has already spread "outward", outside the prostate gland;
  • T3a - seminal vesicles are not affected by the tumor;
  • T3b - seminal vesicles are also affected;
  • T4 - the tumor has not only spread beyond the prostate gland, but also affected nearby organs (but not the seminal vesicles): the rectum, bladder neck, muscles associated with the urethra and sphincter.


Category N


The letter N indicates the presence or absence of metastases in the nearest - pelvic - lymph nodes.


The following notation is used to describe the prevalence of metastases:



  • NX - the condition of the lymph nodes cannot be assessed;
  • N0 - absent in pelvic lymph nodes;
  • N1 - present in the pelvic lymph nodes.


Category M


Category M describes the degree of damage from the neoplasm, that is, it shows whether the prostate tumor has given distant metastases to lymph nodes and organs.


The following conventions are used:



  • MX - insufficient data to determine the presence or absence of distant metastases;
  • М0 - signs of distant metastases were not found;
  • M1 - distant metastases found, in turn, subdivided into clarifying sections;
  • M1a - distant lymph nodes are affected;
  • M1b - bone metastasis detected;
  • M1c - metastases in other organs of the body (lungs, liver, etc.).


Histological classification of prostate cancer in men


When conducting a histological examination of prostate tissue (most often a biopsy), the following forms of oncological formations are distinguished:



  • adenocarcinoma of the prostate;
  • transitional cell carcinoma of the prostate (PCa);
  • squamous cell carcinoma;
  • undifferentiated PCa.

According to studies, adenocarcinoma is the most common: it accounts for more than 90% of malignant tumors of the prostate.


It is also the most well-treated. Patients with other forms of PCa have a worse prognosis. To determine the degree of aggressiveness of adenocarcinoma, the Glisson scale is used: the more the studied cells differ from healthy prostate tissues, the higher the score is "assigned" to them.



Identification of prognostic factors


There are several prognostic factors that can be used to determine the rate at which oncology will grow, what is the likelihood of metastasis, how the tumor will respond to treatment. Biopsy and differentiation of cancer on the Glisson score allows you to answer these questions.


Depending on the amount, several prognostic groups are distinguished:



  • Glisson score 2-6 points - the tumor is low active, cellular changes are insignificant, the prognosis is favorable;
  • Glisson score 7-8 points - average tumor malignancy, relatively favorable prognosis;
  • Glisson score 9-10 points - the tumor is highly malignant, rapidly spreading, with a high probability of metastasis, the prognosis is unfavorable.

In addition, the prognosis is affected by the current state of the body: so, even if the tumor is small, damage to the seminal vesicles significantly worsens the prognosis.



Partin Chart


Partin's graph is a mathematical model that allows you to determine the further course of the disease with 95% accuracy, to understand how the patient will progress with prostate cancer.


To determine the degree of progression, data on the Glisson sum, data on the classification of TNM, as well as the PSA value - the blood level of a specific protein that is a tumor marker of prostate cancer.


The models are based on data from thousands of men undergoing treatment and are updated regularly. Computer programs have been developed to facilitate and speed up the calculation of forecasts.



Nomograms of Kattan


The nomograms were developed on the basis of a huge amount of data collected in clinics in the USA, Canada, and Germany. For example, postoperative nomograms, based on the Glisson sum, information on TNM, and some data on the patient's condition after surgery to remove the tumor, allow us to calculate the probability of recurrence within 7 years.


Other nomograms calculate the probability of a return of the disease after radiation therapy or brachytherapy for 5 years after treatment.



Prognosis for prostate cancer


Unfortunately, it is impossible to predict the course of the disease and its response to various treatments in advance.



Related video


About the classification of prostate cancer in the video:


Studies show that the clinical picture of prostate cancer is extremely wide, and the prognosis depends on the degree of development of prostate cancer at the time of detection of the disease.


The earlier the tumor is detected, the greater the chances for a full recovery, restoration of working capacity and the opportunity to lead a normal life. The higher the stage of the lesion, the more malignant the tumor, the worse the prognosis and the higher the likelihood of death.