Testicular cancer

Testicular cancer is the most common solid cancer of men aged 15-35 years.

The incidence is 2.5-20 times higher in patients with cryptorchidism, even when the unopposed testicle was dropped surgically. Cancer can also develop in a normally lowered testicle. The cause of testicular cancer is unknown.

Epidemiology

Testicular cancer accounts for 0.5% of all malignancies in males, most often occurring between the ages of 15-44 and the leading cause of death among malignant neoplasms in this age group.

Approximately 90-95% of primary testicular tumors are in germinogenic (non-seminal and seminoma) tumors, 5-10% in non-germogenic (leidigoma, sertolioma, gonadoblastoma, etc.). Cancer of the testicle, like cryptorchidism, appears more often in the right testicle. Primary testicular tumors are bilateral in 1-2% of cases. Approximately 50% of patients have a history of single- or double-sided cryptorchidism. Primary bilateral tumors can occur both synchronously and metachronically, but, as a rule, belong to the same histological type. Of primary tumors of the testicle, the bilateral is usually seminal, of the secondary - lymphoma.

At present, there is a steady increase in the incidence of testicular cancer. Over the past 5 years, according to world statistics, it has increased, on average, by 30%.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]

Causes of the testicular cancer

Factors, one way or another leading to testicular atrophy ( cryptorchidism, chemical factors, trauma, idiopathic testicular atrophy, and various infectious diseases) can also provoke testicular cancer. In men with testicular hypotrophy, there is an increased risk of developing testicular cancer.

In normally functioning cells, the p53 protein is practically not detected. It is an important factor affecting cell proliferation and apoptosis. In many malignant tumors, a mutation of the p53 gene is detected. As a rule, the detection of a mutant functionally inactive p53 is an indicator of poor prognosis and resistance to treatment. With germicogenic testicular tumors, increased formation of normal p53 protein is noted. Which, perhaps, explains the unique sensitivity of these tumors to chemo- and radiotherapy.

In most cases, testicular cancer occurs in primordial germinal cells. Tumors of germ cells are characterized as seminomas (40%) or non-seminoma (tumors containing any non-essential elements). Neseminomas include teratomas, fetal cancers, endodermal sinus tumors (yolk sac tumors) and choricarcinomas. Histological combinations are common; for example, teratocarcinoma may include teratoma and embryonic cancer. Functional interstitial cancers are rare.

Even in patients with apparently localized tumors, there may be latent regional or visceral metastases. The risk of metastasis is highest for choriocarcinoma and the lowest for teratoma.

Tumors that occur in epididymis, epididymis, and spermatic cord are usually benign fibroids, fibroadenomas, adenomatous tumors and lipomas. Sarcomas, more often rhabdomyosarcomas, are rare, more common in children.

[12], [13], [14], [15], [16], [17], [18]

Risk factors

• Cryptorchidism is a major risk factor for developing testicular cancer. If the testicle does not descend on the scrotum, the risk of the disease increases by 5 times compared with the general population. The risk is significantly higher (more than 10 times) in men with bilateral cryptorchidism. Against the background of cryptorchidism there are 7-10% of testicular tumors, most often seminalomas. However, in 5-10% of cases, the tumor appears in the normally lowered testicle, on the opposite side.
• Toxicosis of pregnant women, borne by the mother due to hypersecretion of estrogen, or prolonged intake of estrogens during pregnancy, increases the risk of testicular cancer in sons.
• Excess estrogens in the environment due to contamination with pesticides (dioxin, polychlorinated biphenyls, phytoestrogens) also leads to an increase in the incidence of testicular cancer.
• Genetic risk factors. The study of familial cases of testicular cancer confirms their importance in the etiology of neoplasms. With a family history of the disease, the risk of developing testicular cancer for fathers and sons of patients is increased 2-4 times, and for the sick brothers - 8-10 times compared with the general male population. Also considered the possibility of recessive inheritance of testicular cancer.
• Klinefelter's syndrome.
• Contact with tin.
• Infertility.

[19], [20], [21]

Pathogenesis

Factors, one way or another leading to testicular atrophy (cryptorchidism, chemical factors, trauma, idiopathic testicular atrophy, and various infectious diseases) can also lead to the development of testicular cancer. In men with testicular hypotrophy, there is an increased risk of developing testicular cancer.

In normally functioning cells, the p53 protein is practically not detected. It is an important factor affecting cell proliferation and apoptosis. In many malignant tumors, a mutation of the p53 gene is detected. As a rule, the detection of a mutant functionally inactive p53 is an indicator of poor prognosis and resistance to treatment. With germicogenic testicular tumors, increased formation of normal p53 protein is noted, which may explain the unique sensitivity of these tumors to chemo- and radiotherapy.

[22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32]

Symptoms of the testicular cancer

Most patients are treated with volumetric scrotal formation, which is painless or sometimes accompanied by mild pain. In a few patients, bleeding into the tumor can cause acute local pain. Many find testicular cancer on their own, with self-examination or after minor trauma.

Symptoms of testicular cancer consist of symptoms due to the primary tumor and metastases. The earliest symptoms of testicular cancer: an increase in the testicle, a feeling of heaviness in the scrotum, a palpable tumor in the corresponding part of the scrotum.

About 10% of patients go to the doctor for acute pain in the testicle. It is usually caused by a hemorrhage or a heart attack. Pain rarely occurs in the initial stages of the disease and appears with a significant increase in intra-venous pressure, sprouting of the scrotum or spermatic cord, which corresponds to common forms of the disease.

Approximately 10% of patients turn to the doctor with complaints caused by metastases (most often it is back pain due to compression of the spinal roots by metastases in the lumbar lymph nodes). Violation of the outflow of urine through the ureters can lead to the appearance of complaints related to the development of renal failure. In addition, coughing and shortness of breath may occur during lung metastases, loss of appetite, nausea and vomiting in metastases to the lymph nodes located behind the duodenum, bone pain, complaints associated with intestinal obstruction, and swelling of the legs during compression of the inferior vena cava .

Rarely the first symptom of a testicular tumor is hemospermia. Approximately 10% of patients have asymptomatic disease. In this case, the tumor is usually detected by the patients themselves, by the sexual partner or by examination of the testicle injury.

With non-germogenic tumors of the testicle, there may be symptoms of testicular cancer associated with hormonal disorders. With these neoplasms, approximately in every third case there is a gynecomastia caused by the production of a significant amount of chorionic hormone by the tumor tissue.

In addition, adults can reduce libido, impotence and feminization due to hyperestrogenism, and in children - masculinization (macrogensis, pubic hair, voice changes, hirsutism, premature development of bone and muscle systems, frequent erections) due to increased production of androgens by the tumor.

Forms

Histological classification of testicular tumors

• Germinogenic tumors (develop from the seed epithelium).
  • Tumors of one histological structure:
    • seminoma;
    • spermatocyte seminoma;
    • fetal cancer;
    • yolk sac tumor (embryonic cancer of infantile type, tumor of endodermal sinus):
    • polyembryoma;
    • choriocarcinoma;
    • teratoma (mature, immature, with malignant transformation).
  • Tumors of more than one histological type:
    • teratocarcinoma (fetal cancer and teratoma);
    • choriocarcinoma;
    • other combinations.
• Tumors of the stroma of the genital tract.
  • Well differentiated forms:
    • Ledigoma;
    • sertolio;
    • granulosceletal tumor.
  • Mixed forms.
  • Not completely differentiated tumors
• Tumors and tumor-like lesions containing germinative cells and cells of the stroma of the genital tract.
  • Gonadoblastoma.
  • Other.
• Different tumors
  • Carcinoid.
• Tumors of lymphoid and hematopoietic tissue.
• Secondary tumors.
• Tumors of direct tubules, nets of the testicle, epididymis, spermatic cord, capsule. Supporting structures, rudimentary formations.
  • Adenomatous tumor.
  • Mesothelioma.
  • Adenoma.
  • Cancer.
  • Melanotic neuroectodermal tumor.
  • Brenner's tumor.
  • Tumors of soft tissues:
    • embryonic rhabdomyosarcoma;
    • other.
• Unclassified tumors.
• Tumor-like lesions.
  • Epidermal (epidermoid) cyst.
  • Nonspecific orchitis.
  • Nonspecific granulomatous orchitis.
  • Specific orchitis.
  • Malacoplakia.
  • Fibromatous periorhitis.
  • Spermatocytic granuloma.
  • Lipogranulomy.
  • Adrenal remains.
• Other.

The most common forms of testicular tumors

• Seminom. Seminoma accounts for 35% of germigenic testicular tumors. Three histological variants are described, although the prognosis for tumors of the same stage from the histological variant does not depend. The classical seminoma is detected in 85% of all cases of seminoma. It often occurs at the age of 30-40 years. Seminoma in 10-15% of cases reveal the secretion of the chorionic gonadotropin. The anaplastic seminoma is less differentiated compared to the classical one and is 5-10% seminoma. However, as already noted, the prognosis for anaplastic or classical seminoma of the same stage is the same. In 5-10% of cases, the seminal seminal is diagnosed. In more than 50% of cases, the spermatocytic seminoma occurs over the age of 50 years.
• Embryonic testicular cancer accounts for almost 20% of germ cell testicular tumors. The expressed polymorphism of cells and fuzzy boundaries between them are characteristic. Often there are mitoses and giant cells. They can be located in layers or form acinar, tubular or papillary structures. There may be extensive areas of hemorrhage and necrosis.
• Teratoma. The share of teratom is 5% of germicogenic testicular tumors. It can occur both in children and in adults, it is mature and immature. This tumor consists of the derivatives of two or three embryonic sheets. Macroscopically it has cavities of various sizes, filled with gelatinous or mucous contents. In the testicle, it is extremely rare to see mature cystic teratomas (dermoid cysts) typical of the ovaries.
• Choriocarcinoma of the testicles. In pure form, choriocarcinoma is rarely detected (less than 1% of cases). This tumor, as a rule, is small, located in the thickness of the testicle. A cut in the center of the tumor often shows a hemorrhage. Choriocarcinoma is an aggressive tumor prone to early hematogenous metastasis. Extensive dissemination is possible even with a small primary tumor.
• A yolk sac tumor is sometimes called an endodermal sinus tumor, or an immature type of embryonic cancer. This is the most common germ cell tumor in children. In adults, it is usually detected in mixed germinogenic tumors. Tumor secretes AFP
• Polyembryoma is another extremely rare testicular tumor. It contains embryoid bodies that resemble a two-week embryo.
• Mixed germ cell tumors account for 40% of germinogenic testicular tumors. In most cases (25% of germinogenic testicular tumors), they are represented by a combination of teratoma and embryonic cancer (terato-carcinoma). Up to 6% of germicogenic tumors of the testicle are mixed tumors containing elements of seminoma. These tumors are treated as non-seminoma.
• Intracanillular germ cell tumors. In one study in patients with a unilateral germinogenic testicular tumor in 5% of cases in the other testicle, intracanular germ cell tumors (cancer in situ) were detected. This is more than 2 times the frequency of bilateral lesions in primary testicular tumors. The clinical course of intracanular germ cell tumors of the testicle has not been studied. Some patients develop invasive germ cell tumors.

Clinically, the most important is the separation of all germicogenic testicular tumors into seminomas and non-seminomas, which significantly affects the choice of approach to treatment. Further subdivision of non-seminiferous testicular tumors does not play a big role.

The WHO classification (1977), which examines in detail the various histological variants of germinogenic testicular tumors, did not take into account the unity of their origin and the possibility of further differentiation into other morphological types during carcinogenesis.

The new histological classification, proposed in 1992, proceeds from the notion of a single origin of all germicogenic testicular tumors from carcinoma in situ. All germinogenic tumors, with the exception of spermocytoma, are suggested to be called gonocytomas. The latter are subdivided into the seminoma (classical and anaplastic, characterized by a more aggressive course), teratogenic gonocyte and anaplastic germinogenic tumor. Having signs of both seminoma and teratogenic gonocytoma.

The stem cell of the teratogenic gonocytoma is pluripotent and can differentiate into various kinds of teratomas (mature and immature), epiblastoma (in the old classification - embryonic cancer) and extraembryonic elements, which include the yolk sac tumor and choriocarcinoma.

[33], [34], [35], [36]

Classification of the International Group on the Study of Hermetic Tumors

[37], [38], [39], [40]

Neseminomnye germinogennye tumor

• Good forecast (if there are all signs):
  • the level of AFP in blood serum is less than 1000 ng / ml;
  • the level of chorionic gonadotropin in serum is less than 5000 mIU / ml;
  • LDH activity in serum is less than 675 U / l;
  • absence of extragonadal mediastinal tumor;
  • absence of metastases in the liver, bones, brain.
• Moderate forecast (if there are any signs):
  • serum level of AFP 1000-10 000 ng / ml;
  • the level of chorionic gonadotropin in the blood serum is 5000-50 000 mIU / ml;
  • LDH activity in the blood serum 675-4500 U / L;
  • absence of extragonadal mediastinal tumor;
  • absence of metastases in the liver, bones, brain.
• Bad forecast (if there is at least one feature):
  • serum AFP levels greater than 10 000 ng / ml;
  • the level of beta-chorionic gonadotropin in serum is more than 50 000 mIU / ml;
  • the activity of LDH in the blood serum is more than 4500 U / l;
  • presence of extragonadal mediastinal tumor;
  • presence of metastases in the liver, bones, brain.

Seminames

• Good prognosis: absence of metastases in the liver, bones, brain.
• Moderate prognosis: the presence of metastases in the liver, bones, brain.

Thanks to the appearance of new cytostatics and the development of new regimens of polychemotherapy, survival in testicular tumors is statistically significantly increased. The five-year survival rate increased from 78% in 1974-1976 to 91% in 1990-1995.

Diagnostics of the testicular cancer

On examination, asymmetry of the scrotum is often determined. Sometimes the second testicle is not visible because of a sharp increase in the other, affected by the tumor. With inguinal retention, the testicular tumor has the appearance of a dense or globular protrusion in the inguinal region. Typically, tumors are defined as dense formations with a smooth, bumpy surface.

In secondary hydrocephalus, the tumor has a soft-elastic consistency. You also need to feel the spermatic cord, sometimes you can determine the transition of the tumor from the testicle to the spermatic cord. Often, testicular tumors are painless on palpation.

Laboratory Diagnosis of Testicular Cancer

Currently, there are three main indicators in the diagnosis of germ cell testicular tumors: AFP, beta-hCG and LDH.

The determination of the level of tumor markers allows us to assume the histological structure of the germinogenic tumor.

Groups of testicular neoplasms depending on the concentration of markers.

• A group of tumors that do not produce AFP and the beta-subunit of hCG. These include seminomas, mature teratomas and embryonic carcinomas of pure type. Among cells of embryonic cancer, giant cells of syncytiotrophoblast can be contained, which produce an insignificant amount of hCG.
• A group of marker-producing tumors. They include about 80% of germinogenic tumors (yolk sac tumors that produce AFP, choriocarcinomas that secrete HCG, mixed tumors that produce AFP and / or hCG).

Considering the essential differences in the therapeutic approach to seminiferous and non-seminiferous testicular tumors, the determination of the level of AFP and hCG is of great practical importance. Often tumor markers are more revealing than routine histological examination of the tumor.

An increase in the serum AFP level in a patient with seminoma without metastases to the liver should be regarded as a sign of the presence of the elements of the yolk sac in the tumor. An increase in the concentration of hCG is found in 15% of patients with seminoma because of the presence of non-seminoma elements in the tumor or, more rarely, the presence of giant cells of syncytiotrophoblast.

If the level of hCG does not exceed the upper limit of the norm at the stage I-II of the seminoma, the therapeutic approach should not be changed. However, in the case of a rise in serum HCG with a primary tumor of a small size or incompatible with its level of giant cells of syncytiotrophoblast in a tumor, it is necessary to regard the disease as a tumor of a mixed structure and to change the treatment regimen.

In addition, an increase in the level of AFP and hCG in the presence of unchanged testes allows one to suspect an extragonadal germogenic tumor in the early stages.

Determining the concentration of tumor markers of blood serum before and after 5-6 days after removal of the primary tumor allows us to clarify the clinically established stage of the disease, which allows us to reduce the error rate by 35%.

The level of tumor markers is determined in all patients with germinogenic tumors during treatment and observation at certain intervals depending on the degree of prevalence of the disease. After radical removal of the tumor, the level of markers should decrease to normal values in accordance with their half-lives (AFP less than 5 days, hCG - 1-2 days).

If the increased concentrations of AFP and hCG and the increase in the half-life of markers after removal of the primary tumor, even in the absence of X-ray data indicative of dissemination of the process, one should think about the presence of distant metastases and appropriate treatment.

An increase in the concentration of AFP and hCG may indicate a progression of the disease 1-6 months before the clinical appearance of relapse and serves as the basis for the initiation of treatment. Diagnostic sensitivity of AFP and hCG in relapses of germicidal tumors is 86% with a specificity of 100%.

The normal level of markers does not allow one to exclude the progression of the disease unequivocally. The recurrent tumor is capable of acquiring new biological properties, for example becoming a marker-negative. False negative results of the study of the concentration of tumor markers in blood serum can be obtained with a small size of the tumor or the presence of a mature teratoma.

Rarely false-positive results in determining the level of AFP and hCG are due to lysis of tumor cells in response to intensive chemotherapy. An increase in the concentration of AFP, not associated with the progression of the disease, may also be due to liver failure.

[41], [42], [43], [44], [45], [46], [47], [48], [49]

Instrumental Diagnosis of Testicular Cancer

In order to verify the diagnosis of "testicular cancer" in complex diagnostic cases, an aspiration biopsy is performed with a cytological examination of the punctate, although this carries the risk of implantation metastases. When doubting the correctness of the established diagnosis, perform an explorative operation with urgent histological examination.

The main methods of diagnosis of testicular tumor metastases include chest X-ray, ultrasound, CT of the abdominal cavity, retroperitoneal space and thorax.

When planning retroperitoneal lymphadenectomy in patients with large residual tumor masses involving major vessels, angiographic studies are performed (aortography, lower one- and two-projection kavografiya).

Differential diagnosis

A hydrocele can hamper the diagnosis of testicular cancer. To distinguish hydrocele from a tumor helps diafanoscopy, ultrasound.

Recently, high hopes are placed on PET, which allows to differentiate a viable tumor from sclerized tissues with a high degree of reliability.

[50], [51], [52], [53], [54], [55], [56], [57], [58], [59]

Treatment of the testicular cancer

Radical inguinal orchahedge, the cornerstone of treatment, provides important histopathological information, especially about the proportion of histological types and the presence of intratumoral vascular or lymphatic invasion. Some patients may be candidates for economical (partial) orchiectomy. Information obtained during surgery helps to plan further treatment and can accurately predict the risk of hidden metastases to the lymph nodes. Thus, it helps to identify which low-risk patients with normal radiologic and serological data, especially those with non-seminoma, may be candidates for surveillance with frequent identification of serological markers, chest x-ray and CT.

Seminomas recur in approximately 15% of these patients and can usually be cured by radiation if they are small, or chemotherapy - if large. Relapses with nonsemine are quickly treated with chemotherapy, although delayed retroperitoneal lymphadenectomy may be an adequate approach for some of them.

Standard treatment for seminoma after unilateral ejachemia is radiation therapy, usually 20-40 Gy (a higher dose is used for patients with lymph node involvement) on the para-aortic areas before the diaphragm, and the ipsilateral iliac-inguinal region is usually not included. Sometimes the mediastinum and the left supraclavicular region are also irradiated, depending on the clinical stage. For nonseminomas, many consider it to be standard treatment for retroperitoneal lymphadenectomy; for early tumors economical (preserving the nerve plexus) dissection is possible. Alternatives include surveillance for stage I tumors without factors predicting a relapse.

During orchiectomy, almost 30% of patients with non-seminoma have microscopic retroperitoneal lymph node metastases. The retroperitoneal lymph nodes of medium size may require retroperitoneal lymphadenectomy and chemotherapy (for example, bleomycin, etoposide, cisplatin), but the optimal sequence is not established.

Laparoscopic lymph node dissection is at the stage of study. The most common negative effect of lymphadenectomy is a violation of ejaculation. If the tumor volume is small, and economical dissection is possible, ejaculation is usually maintained. Fertility often worsens, but with the development of pregnancy no risk to the fetus has been identified.

A cosmetic testicular prosthesis can be implanted during orchocheia, but they are not widely available due to already known problems with breast silicone implants. However, an implant based on physiological saline was developed.

The defeat of lymph nodes larger than 0.1 cm, metastases to the lymph nodes above the diaphragm or visceral metastases require an initial combination chemotherapy based on platinum drugs followed by surgery for the remaining lymph nodes. Such treatment usually controls tumor growth for a long time.

Treatment of seminoma tumors in stage I

Approximately 15-20% of patients with seminoma stage I already have metastases, most often in the retroperitoneal space, which are the cause of the relapse of the disease.

• Operative treatment of testicular cancer. The retroperitoneal lymphadenectomy is not indicated in the first stage of seminoma due to high risk (9.5%) of retroperitoneal relapses.
• Radiation therapy
  • Since seminaloma cells have unique radiosensitivity, adjuvant radiation therapy is indicated for para-aortic zones up to 20 Gy. Which allows to reduce the frequency of recurrence up to 1-2%.
  • After radiation therapy, relapse is possible, first of all, outside the irradiated area (in the supra-diaphragmatic lymph nodes or lungs). Adjuvant radiotherapy for para-aortic zones is the standard treatment for patients with stage I of testicular semenoma, as well as T1-T3 and unrelated lymph nodes. The incidence of recurrence in the iliac lymph nodes is 2% when irradiating only the para-aortic zones. Adjuvant radiation therapy on the zone of the supra-diaphragmatic lymph nodes is not indicated in stage I of the seminoma.
  • Complications of moderate severity from the GI tract occur in 60% of patients. Five-year recurrence-free survival is about 80%. In multivariate analysis of the prognosis, the tumor size greater than 4 cm, as well as invasion of the testicle shells, is of greatest significance with respect to the occurrence of relapse. The frequency of recurrence is 15-20%. Most often, relapse occurs in the subdiaphragmatic lymph nodes. In 70% of patients with relapse, only radiation therapy is possible. After radiation therapy, only a 20% of patients develop a relapse that requires chemotherapy. The total cancer-specific survival rate for stage I seminoma is 97-100%. Although 70% of relapses occur within the first 2 years after orhfunicullectomy, in 7% of patients relapse occurred 6 years after diagnosis.
• Chemotherapy
  • Between carboplatin chemotherapy and radiotherapy, there are no significant differences in the frequency of recurrence, time to relapse, and survival with a median follow-up of 3 years.
  • Thus, adjuvant chemotherapy with carboplatin is an alternative to radiotherapy for stage I seminoma in terms of survival. Carrying out two courses of carboplatin can reduce the frequency of recurrence.

Treatment of seminoma tumors in stage IIA and IIB

• Radiation therapy is the standard treatment for seminoma of stages IIA and IV (radiation dose 30 and 36 Gy, respectively). In the irradiation zone, as compared with the standard in stage I, the ipsilateral iliac zone is included. At stage IIB, the area of the metastatic lymph node with a safety zone of 1.0-1.5 cm is included in the irradiation zone. This technique allows achieving a 6-year disease-free survival rate of 95% and 89% in stages IIA and IIB, respectively. The overall survival rate is 100%.
• Chemotherapy
  • At stage IIB, chemotherapy may be carried out according to the scheme of the 3rd course of the VEP or the 4th course of EB in patients with a good prognosis as an alternative to radiation therapy in case of patient's refusal.
  • Platinum-containing regimens of "saving" chemotherapy can be effective in 50% of patients in case of relapse or insensitivity after first-line chemotherapy.
  • Basic chemotherapy regimens:
    • 4 courses according to the PEI VIP scheme, which includes cisplatin, etoposide, ifosfamide.
    • 4 courses of VelP, including vinblastine, ifosfamide, cisplatin.

PEI scheme every 3 weeks

A drug	Dose	Day	Duration of the course
Cisplatinum	20 mg / m 2	1-5	21 day
Etoposide	75-100 mg / m 2	1-5
Ifosfamide	1.2 g / m 2	1-5

VelP scheme every 3 weeks

A drug	Dose	Day	Duration of the course
Vinblastine	0.11 mg / kg	1-2	21 day
Ifosfamide	1.2 g / m 2	1-5
Cisyalatin	20 mg / m 2	1-5

Further management

Patients after chemotherapy or radiotherapy with testicular seminaloma of stage I need further long-term follow-up.

Dynamic observation of stage I seminaloma after chemotherapy or radiotherapy

Procedure	Year
	1	2	3	4-5
Clinical examination	6 times	4 times	3 times	2 times per year
Chest X-ray	6 times	4 times	3 times	2 times per year
Study of markers	6 times	4 times	3 times	2 times per year
CT of abdominal cavity	1 time	1 time	According to the testimony	According to the testimony
Ultrasound of the abdominal cavity	1 time*	1 time*	1 time	According to the testimony

* Perhaps instead of CT of the abdominal cavity

Dynamic observation at testicular seminaloma of stage I with tactic of careful observation

Procedure	Year
	1	2	3	4-5	6-10
Clinical examination	6 times	4 times	3 times	2 times per year	1 time per year
Chest X-ray	6 times	4 times	3 times	2 times per year	1 time per year
Study of markers	6 times	4 times	3 times	2 times per year	1 time per year
CT of abdominal cavity	4 times	4 times	According to the testimony	According to the testimony	According to the testimony
Ultrasound of the abdominal cavity		1 time	1 time	According to the testimony	According to the testimony

Dynamic observation with seminoma of stage IIA-IIB after radiotherapy.

Procedure	Year
	1	2	3	4-5	6-10
Clinical examination	6 times	4 times	Z times	2 times per year	1 time per year
Chest X-ray	6 times	4 times	Z times	2 times per year	1 time per year
Study of markers	6 times	4 times	Z times	2 times per year	1 time per year
CT of the abdominal cavity and pelvis	According to the testimony	According to the testimony	According to the testimony	According to the testimony	According to the testimony
CT of thorax	According to the testimony	According to the testimony	According to the testimony	According to the testimony	According to the testimony

Treatment of non-seminoma tumors in stage I

In patients with non-seminary tumors of testicle stage I, subclinical metastases exist in 30% of cases and relapses may occur after performing orhfunicullectomy.

Using a number of prognostic signs, it is possible to divide patients according to the risk of developing metastases. The main indicator of relapse in patients of stage I is vascular invasion by tumor cells in the primary tumor. In a low-risk group, patients are referred to without vascular invasion and tumor germination into the vaginal sheath of the testicle. In the group of patients with vascular invasion, with a proliferation level of more than 70% and a tumor cell composition of more than 50% of embryonic carcinoma in the tumor, the risk of developing metastatic lesions is 64% (high-risk group).

• Chemotherapy
  • If careful dynamic observation is not possible in low-risk patients, it is possible to perform nerve-sparing retroperitoneal lymphadenectomy or 2 courses of chemotherapy according to the BEP scheme (cisplatin, etoposide, bleomycin). If, with retroperitoneal lymphadenectomy, metastatic lymph node involvement is detected, the patient is shown 2 courses of adjuvant chemotherapy according to the BEP scheme (cisplatin, etoposide, bleomycin).
  • Patients with poor prognosis are shown active treatment of testicular cancer: 2 courses of neoadjuvant chemotherapy according to the BEP scheme (cisplatin, etoposide, bleomycin)
• Operative treatment of testicular cancer. If chemotherapy can not be performed or the patient refuses to show it, nerve-sparing retroperitoneal lymphadenectomy or dynamic observation with operative treatment of testicular cancer in the case of relapse develops.

80% of relapses are detected during the first year of observation, 12%. During the 2nd year and 6% - during the 3rd year. The frequency of recurrence is reduced to 1% during the 4th and 5th year, occasionally they occur later. In a third of patients with relapse, the level of serological markers is normal. 60% of relapses occur in the retroperitoneal space.

Treatment of non-seminoma tumors in stage II

Three courses of chemotherapy according to the BEP scheme (cisplatin, etoposide, bleomycin) are shown.

Patients with non-seminoma tumors of stage IIA and IIB and an increase in the level of serological markers should be treated with testicular cancer in accordance with the prognosis groups. Patients from the moderate and good prognosis groups are shown to conduct the 3rd or 4th courses of neoadjuvant chemotherapy according to the BEP scheme followed by removal of the residual tumor. Approximately 30% of patients do not achieve complete regression of the tumor during chemotherapy, so they are shown to perform retroperitoneal lymphadenectomy.

Patients who refused chemotherapy at the first stage showed nerve-preserving retroperitoneal lymphadenectomy followed by 2 courses of adjuvant chemotherapy according to the BEP scheme for the detection of metastatic lymph node involvement.

• Chemotherapy. Chemotherapy in the first stage is carried out by patients in accordance with the IGCCCG, 3rd or 4th year forecasting groups according to the BEP scheme. This regimen is more effective than PVB (cisplatin, vinblastine, bleomycin) in patients with advanced forms of the disease. The three-day schedule of prescribing the drug has a similar efficacy, but is associated with a higher toxicity.

The VER scheme every 3 weeks

A drug	Dose	Day	Duration of the course
Cisplatinum	20 mg / m 2	1-5	21 day
Etoposide	100 mg / m 2	1-5
Bleomycin	30 mg / m 2	1-8-15

Chemotherapy depending on the prognosis of the disease.

• Group of good prognosis. The standard therapy is considered to be 3 courses according to the BEP scheme or 4 courses of PE (for contraindications to the use of bleomycin). The drugs are used every 22nd day without reducing the dose. Postponement of the beginning of the next course is possible only in the presence of a fever, the number of neutrophils of blood less than 1000 in 1 ml. Platelets less than 100,000 in 1 ml on the 1 st day of the appropriate course. Granulocyte colony-stimulating factor is not prescribed for prophylactic purposes. However, in case of occurrence of infectious complications during chemotherapy, it is recommended to prophylactically prescribe a granulocyte colony-stimulating factor during subsequent
• Group of moderate prognosis. The standard therapy is 4 courses according to the scheme of the VER
• Group of poor prognosis. Assign 4 courses of chemotherapy according to the BEP scheme. The 4-year schedule of PEI (cisplatin, etoposide, ifosfamide) has the same efficacy, but significantly higher toxicity. The five-year recurrence-free survival rate is 45-50%. Until now, there is no evidence of improvement in the administration of drugs in high doses.

Operative treatment of testicular cancer

With complete remission of non-seminoma tumors after chemotherapy, removal of residual tumors is not indicated. In the presence of residual masses over 1 cm in transverse dimension, CT surgery and normalization of the level of markers show operative treatment of testicular cancer. At the end of the initial chemotherapy, only 10% of residual masses contain viable tumor cells, 50% - mature teratoma and 40% - necrotic masses. Thus, removal of residual masses after initial chemotherapy is considered mandatory in non-seminiferous tumors.

After the completion of two courses of chemotherapy, a reassessment of the detected formations and the level of serological markers is necessary. At a normal level of markers and stabilization or regression of tumor manifestations, chemotherapy must be completed (3rd or 4th year in accordance with the initial stage of the process). When the level of markers is normalized, but the progression of metastases requires the mandatory removal of residual formations after the abolition of initial chemotherapy. "Saving" chemotherapy is indicated only with a proven increase in the level of markers after completing two courses of chemotherapy.

The final chemotherapy (2 courses with platinum-containing drugs) is shown after operative treatment of testicular cancer in case of detection of viable tumor cells or mature teratoma in a planned pathomorphological study.

"Saving" chemotherapy is carried out in case of resistance of the tumor to the first line of therapy or relapse after "saving" surgery (4 courses according to PEI / VIP scheme).

Further management

The absence of vascular invasion has a negative predictive value of about 80%, which allows patients of stage I to be left under close supervision.

Patients who refused chemotherapy at the first stage after nerve-sparing retroperitoneal lymphadenectomy followed by 2 courses of adjuvant chemotherapy according to the BEP scheme in detecting a metastatic lesion of lymph nodes showed dynamic observation.

Dynamic observation in non-seminiferous testicular tumors of stage I after retroperitoneal lymphadenectomy or adjuvant chemotherapy

Procedure	Year
	1	2	3-5	6-10
Clinical examination	6 times	3 times	2 times per year	1 time per year
Chest X-ray	6 times	3 times	2 times per year	1 time per year
Study of markers	6 times	3 times	2 times per year	1 time per year
CT of abdominal cavity	2 times	1 time	According to the testimony	According to the testimony
Ultrasound of the abdominal cavity *	2 times	2 times	2 times per year	1 time per year

* Perhaps instead of CT of the abdominal cavity.

Dynamic observation in non-seminoma tumors of stage IIA-IIB after retroperitoneal lymphadenectomy or chemotherapy

Procedure	Year
	1	2	3-5	6-10
Clinical examination	1 time in 2 months	4 times	2 times per year	1 time per year
Chest X-ray	1 time in 2 months	4 times	2 times per year	1 time per year
Study of markers	1 time in 2 months	4 times	2 times per year	1 time per year
CT of abdominal cavity	2 times	2 times	According to the testimony	According to the testimony
Ultrasound of the abdominal cavity *	2 times	2 times	According to the testimony	According to the testimony

* - Perhaps instead of CT of the abdominal cavity.

Forecast

Testicular cancer has a different prognosis, which depends on the histological structure and prevalence of the tumor. 5-year survival is more than 95% for patients with seminoma or non-seminoma localized in the testicle, or with small-sized non-seminoma and metastases in the retroperitoneal space. 5-year survival for patients with extensive retroperitoneal metastases, with pulmonary or other visceral metastases - from 48% (for some nonseminate) to more than 80%, depending on the area, volume and histological structure of the metastases. However, even patients with advanced disease when treated can be cured.

For the prognosis and standardization of treatment approaches, there are several classifications according to the extent of the spread of the disease (European Organization for Research and Treatment of Bladder Cancer, etc.).

In 1995, a new classification of the International Group for the Study of Hermetic Tumors was proposed, which divides disseminated germinogenic testicular tumors into prognostic groups, recognized by most major centers for the treatment of disseminated testicular tumors. In the classification of IGCCCG, the concentration of tumor markers in serum is used as a prognostic factor in germinogenic testicular tumors.

[60], [61], [62], [63]