TESTICULAR CANCER TREATMENT IN GERMANY

Testicular cancer is the most common solid malignancy in men aged 20–40. In patients with cryptorchidism it occurs 2.5–20 times more often. The increased risk is reduced or eliminated if orchiopexy is performed before the age of 10. Cancer may also arise in the orthotopic contralateral testicle. The causes of testicular cancer are unknown.

Most tumours arise from primordial germ cells. Germ cell tumours are divided into seminomas (40%) and non-seminomas (tumours containing any non-seminomatous components). Non-seminomatous tumours include teratoma, embryonal carcinoma, endodermal sinus tumours (yolk sac tumours) and choriocarcinoma. Mixed histological variants are common: teratocarcinoma, for example, contains elements of both teratoma and embryonal carcinoma. Functioning interstitial cell carcinoma of the testis is rare.

Even patients with presumed localised tumours may have occult lymphatic or visceral metastases. For example, almost 30% of patients with non-seminomatous tumours may develop lymph node recurrence or visceral metastases if they receive no treatment after orchiectomy. The risk of metastasis is highest in choriocarcinoma and lowest in teratoma.

Tumours arising from the epididymis, the testicular appendix and the spermatic cord are usually benign fibromas, fibroadenomas, adenomatoid tumours and lipomas. Sarcoma, most often rhabdomyosarcoma, is rare and occurs mainly in children.

CAUSES OF TESTICULAR CANCER

There is no single definite cause of testicular cancer, but there are risk factors:

• cryptorchidism (failure of the testicle to descend into the scrotum);
• hereditary factors;
• place of residence (the incidence is higher in Switzerland and Denmark; lower in China and among black Africans)
• injury to the testicle.

SYMPTOMS AND CLINICAL PRESENTATION OF TESTICULAR CANCER

In most patients the disease presents as a mass in the scrotum, sometimes painless, sometimes associated with a dull, aching pain. In some patients bleeding into the tumour can cause acute local pain. Many patients find the mass themselves after a minor scrotal injury. The main sign of testicular cancer is a firm mass in the scrotum that gradually increases in size. In the early stages a man may not notice anything wrong, because there is neither pain nor malaise. In such cases only a timely examination will detect the tumour.

As the tumour grows, further symptoms may appear:

• pain in the abdomen and the scrotum;
• enlargement and deformity of the testicle.

The disease is also accompanied by the general symptoms of cancer:

• rapid fatigue and weakness;
• weight loss;
• low-grade fever.

DIAGNOSIS OF TESTICULAR CANCER

• ultrasound of scrotal masses;
• physical examination if a mass is present;
• staging by CT of the abdomen, pelvis and chest, together with histological examination.

Many patients find the mass themselves during self-examination. Young men should be advised to perform monthly testicular self-examination.

The origin and nature of a scrotal mass must be established precisely, since most masses within the testicle are malignant whereas most extratesticular masses are benign; telling them apart on physical examination can be difficult. Scrotal ultrasound can confirm that the mass lies within the testicle. If a testicular mass is confirmed, the serum concentrations of the tumour markers α-fetoprotein and β-human chorionic gonadotropin must be measured and a chest X-ray taken. Inguinal exploration is then indicated; the spermatic cord is freed and clamped before any manipulation of the affected testicle.

If the diagnosis of testicular cancer is confirmed, CT of the abdomen, pelvis and chest must be performed for clinical staging according to the standard TNM system, with testicular cancer additionally staged by the TNMS system using serum markers. Tissue removed at surgery (usually radical inguinal orchiectomy) provides important histopathological information, in particular on the proportions of the histological components of the tumour and on intratumoural lymphovascular invasion. This information makes it possible to predict the risk of occult lymphatic and visceral metastases. Patients with non-seminomatous tumours carry an approximately 30 per cent risk of recurrence despite normal imaging findings, normal serum marker levels and an apparently localised process. In such patients seminomas recur in approximately 15% of cases.

TYPES OF TESTICULAR CANCER

Detailed differential diagnosis serves to classify tumours into the following types:

• germ cell tumours — involving the germinal structures of the testicle;
• non-germ cell masses — tumours of the testicular stroma;
• mixed lesions of healthy testicular and scrotal tissue — tumours made up of both germ cell and non-germ cell components.

Germ cell tumours are in turn divided into:

• seminomas (spermatocytic, anaplastic, classic);
• non-seminomas (embryonal cell carcinoma, chorionepitheliomas, choriocarcinomas, teratoblastomas, teratomas).

Non-seminomas (non-seminomatous tumours) are most often diagnosed in young men — between the ages of 20 and 35. They develop quickly, metastasise and involve other organs. They may include yolk sac tumours, lymphomas and others. The prognosis for this type of tumour is favourable in 93% of cases, provided the patient sees a urological oncologist in good time.

Seminomas affect men over the age of 40. They grow slowly, do not involve other organs and usually cause no pain. Unlike non-seminomas, they follow a favourable course. If treatment is started in good time, patients are cured in 99% of cases.

Non-germ cell tumours are in turn divided into the following subtypes:

• Leydig cell tumours;
• Sertoli cell tumours;
• sarcomas;
• dysgerminomas.

By stage of development the disease is divided into the following groups:

1. the tumour does not extend beyond the testicle;
2. the tumour involves the lymph nodes;
3. the tumour involves the cervical lymph nodes.

About 90% of all testicular tumours are malignant germ cell tumours. The remaining 10% are mainly benign tumours arising from Leydig and Sertoli cells. Only very rarely are these tumours malignant. Germ cell tumours of the testicle develop from a pluripotent stem cell that turns into a malignant cell in response to various endogenous, exogenous, hormonal and genetic events. This transformation initially produces a pre-invasive precursor, carcinoma in situ or intratubular germ cell neoplasia, which is the precursor of all germ cell tumours except spermatocytic seminoma, but which cannot yet metastasise on its own.

If a patient has already been diagnosed with a tumour in one testicle, there is a high risk of a second tumour developing on the opposite side. For this reason, when certain risk factors are present, a tissue sample is taken from the apparently healthy testicle as part of primary treatment in order to assess this risk. Otherwise, patients should regularly perform testicular self-examination and undergo an ultrasound examination once a year.

Testicular cancer treatment in Germany — the key to a good prognosis.