Testicular cancer: symptoms, self-examination, diagnosis and treatment

Testicular cancer is the most common malignancy in males aged 15 to 40, yet it has one of the highest cure rates in oncology. In the great majority of cases it is a germ cell tumour (GCT), arising from the cells that give rise to sperm. Early diagnosis and treatment in experienced centres are the keys to success: this is why testicular self-examination is the single most important prevention tool.

How common it is

Germ cell tumours account for about 1-1.5% of all male cancers, with an incidence of 3-6 new cases per year per 100,000 men in Western countries and a rise observed in recent decades. In Italy, testicular cancer is the most frequent malignancy (11%) in males under 50 (source: AIOM/AIRTUM Cancer Registry). About 95% are primary testicular tumours; in the remaining 5% the origin is extragonadal (most often mediastinum or retroperitoneum). About 40% are pure seminoma, roughly 60% are non-seminomatous or mixed forms: the key distinction, because it drives the whole treatment.

Risk factors

The well-defined risk factors for testicular cancer are:

• Cryptorchidism (undescended testis), including in the past history
• Previous tumour in the opposite testis or testicular intraepithelial neoplasia (TIN)
• Hypotrophic testis (reduced in volume)
• Klinefelter syndrome
• Family history of testicular cancer in first-degree relatives

Infertility or reduced fertility also appear to play a role, still under study. Having one or more risk factors does not mean it is certain the disease will develop.

Most germ cell tumours arise from a precancerous lesion, testicular intraepithelial neoplasia (TIN), regarded as their common precursor. TIN is present in 0.5-1% of fertile males but rises to 2-4% in cryptorchid testes: one more reason for surveillance in those who have had cryptorchidism. The relationship between TIN and the actual development of a tumour is, however, still debated.

Symptoms and self-examination

Testicular cancer typically presents as a hard, painless nodule within the testis, or as an increase in firmness or volume of a testis. Precisely because it is often painless, it can go unnoticed: this is why periodic self-examination is essential, just as breast self-examination is for women.

Self-examination is done with the testicles warm and relaxed (for example after a warm shower), gently rolling each testis between thumb and fingers, looking for nodules, hardening or changes in size or firmness. Any nodule or change should be shown promptly to a specialist.

Diagnosis

Testicular cancer is generally suspected at the clinical examination. The diagnostic pathway follows well-defined steps:

• Testicular ultrasound: confirms the clinical suspicion
• Serum tumour markers: alpha-fetoprotein (AFP), beta human chorionic gonadotropin (beta-HCG) and LDH. After radical removal of the tumour, AFP should normalise within 5-7 days and beta-HCG within 1-2 days: a useful indicator of the completeness of surgery
• Histological diagnosis: definitive confirmation comes from examining the testis removed by inguinal orchiectomy. Intraoperative biopsy is rarely needed
• Staging with CT of chest, abdomen and pelvis, with particular attention to the retroperitoneal lymph nodes (in stage I seminoma, chest CT may be replaced by a chest X-ray)

Organ-preserving surgery is possible only in very selected cases (for example small synchronous bilateral tumours without rete testis invasion, or in men with a single testis).

Preserving fertility: a point not to forget

In these patients, often young and of reproductive age, alterations of the semen — and sometimes of testicular hormone function — are frequently found already at diagnosis. For this reason, at diagnosis and possibly before orchiectomy, an andrological visit, measurement of FSH, LH and total testosterone, and a semen analysis should be carried out. Sperm cryopreservation should be discussed with the patient before any treatment (surgery, chemotherapy, radiotherapy) that could impair fertility. It is a choice to be addressed early, while all options are still open.

Staging

The TNM classification is used to define the stage. In brief: stage I means disease confined to the testis after orchiectomy (the IS variant has still-elevated markers); stage II increasing involvement of the retroperitoneal lymph nodes (IIA under 2 cm, IIB 2-5 cm, IIC over 5 cm); stage III the presence of distant metastases. In metastatic disease the international prognostic classification IGCCCG is also used, distinguishing three prognostic categories (good, intermediate, poor) on the basis of histology, tumour markers and disease sites.

Treatment

Treatment of testicular cancer is multidisciplinary and integrates, according to type (seminoma or non-seminoma), stage and risk class, four tools: surgery (orchiectomy), active surveillance, chemotherapy and radiotherapy. The first step is almost always inguinal orchiectomy (removal of the affected testis); the subsequent strategy depends on the stage.

Stage I: confined disease

The prognosis is excellent, with survival close to 100%. After orchiectomy the choices differ by histology:

• Seminoma: up to 15-20% of patients have micro-metastases that are not visible. Active surveillance avoids over-treating the large majority already cured by surgery alone; alternatively, a single cycle of carboplatin chemotherapy is possible. Radiotherapy, once standard, is now generally avoided because of the risk of second cancers. The factors that raise the risk of relapse are a tumour larger than 4 cm and rete testis invasion
• Non-seminoma: overall survival is about 99%. The main risk factor for relapse is vascular invasion. In its absence (low risk) surveillance is preferred; in its presence (high risk) a cycle of chemotherapy (PEB) or, in experienced centres, retroperitoneal lymphadenectomy is used

Stage II and advanced disease

In stage II (retroperitoneal nodes), chemotherapy, radiotherapy (in seminoma) or retroperitoneal lymphadenectomy is used, depending on type and extent. In advanced or metastatic disease, first-line treatment is chemotherapy (PEB regimen), with the number of cycles modulated according to the IGCCCG prognostic category, followed where necessary by surgery of residual masses.

The choice between the available options, with their respective benefits and side effects, should always be discussed with the patient and entrusted to a centre with specific experience: the centre's experience directly affects the oncological result, especially in poorer-prognosis cases.

Prognosis and curability

Testicular cancer is one of the solid tumours with the highest curability. In stage I, survival is close to 100%; even in advanced disease a very high proportion of patients are cured thanks to chemotherapy. Even in forms that relapse after first treatment, salvage chemotherapy achieves durable remissions in a significant share of cases. Prognosis depends on the histological type, the stage at diagnosis and the risk category.

Follow-up

A prolonged follow-up is planned after treatment. Most relapses occur in the first two years, so surveillance is more intensive in this phase, but continues with annual checks even beyond five years (in seminoma relapses tend to be more spread over time). Each check includes testicular palpation; in higher-risk patients (history of cryptorchidism, testicular atrophy, infertility) periodic scrotal ultrasound is indicated, even beyond 5 years. Follow-up also monitors the long-term effects of treatment (second cancers, cardiovascular and renal problems, hearing disorders, metabolic syndrome, gonadal function), whose prevention is an integral part of care.

Non-germ cell testicular tumours

About 5% of testicular tumours are not of germ cell origin. This group mainly includes gonadal stromal tumours:

• Leydig cell tumour: the most frequent form (about 3% of adult testicular tumours, also found in children aged 6 to 9). It can hormones and cause gynaecomastia in adults or precocious pseudopuberty in children. No more than 10% of forms are malignant
• Sertoli cell tumour: the second most frequent (about 1% of testicular tumours), typical of adults

There are also lymphomas, more frequent in older men, which pose a differential diagnosis with seminoma. In stromal forms, often small and found incidentally on ultrasound, testis-sparing surgery is possible in many cases, reserving radical orchiectomy for bulky tumours or unfavourable features.

Frequently asked questions about testicular cancer

How do you perform testicular self-examination?

It is done with the testicles warm and relaxed, for example after a warm shower, gently rolling each testis between thumb and fingers, looking for nodules, hardening or changes in size and firmness. It should be done regularly, because testicular cancer is often painless and self-examination is the most effective way to notice it early. Any change should be shown to a specialist.

Is a testicular lump always cancer?

No. Many scrotal swellings are benign (hydrocele, cysts, varicocele). However, a hard nodule inside the testis, especially if painless, should always be assessed without delay with examination and ultrasound: distinguishing a benign from a malignant form requires a specialist. Do not wait for the lump to disappear on its own.

Can testicular cancer be cured?

Yes. It is one of the solid tumours with the highest probability of cure. In early stages, survival is close to 100%, and even in advanced forms a very high proportion of patients are cured thanks to chemotherapy. Early diagnosis and treatment in an experienced centre remain decisive.

After removal of a testis, do you stay fertile and keep your virility?

In most cases a single healthy testis is enough to ensure normal testosterone and sperm production. However, because chemotherapy and radiotherapy can reduce fertility, it is important to discuss sperm cryopreservation before starting treatment. Removing one testis does not in itself impair sexual activity.

Does cryptorchidism increase the risk of testicular cancer?

Yes, an undescended testis (cryptorchidism) is a well-defined risk factor, even when corrected in childhood. In a cryptorchid testis the precancerous lesion of germ cell tumours (TIN) is present in 2-4% of cases. For this reason, anyone who has had cryptorchidism should pay particular attention to self-examination and, where appropriate, periodic checks. You can read more on the page dedicated to the undescended testis.

Have you noticed a lump or a change in a testis? Do not wait: ask Prof. Natali for a consultation or book an appointment at his practices in Florence and Empoli, Italy.

The information on this page is provided for general educational purposes and does not replace a medical examination, which remains the only diagnostic tool for correct and effective treatment.