Prof. Giacomo Novara β Urology, University of Padova
Germ cell neoplasms β Seminomas and non-seminomas
Incidence has been increasing over recent decades, both through clinical perception and epidemiological data. One-year survival exceeds 96%; 5-year survival is approximately 93%. Precisely because these patients do not die, the therapeutic approach is oriented towards reducing side effects over the course of a still very long life ahead.
The testes originate embryologically in the retroperitoneum and migrate towards the scrotum during intrauterine life. Failure to complete this migration β cryptorchidism β confers an approximately 10-fold increased risk of germ cell neoplasm compared with the general population, even after orchidopexy performed within 12β24 months of life.
Incidental detection of testicular nodules during ultrasound work-up for infertility is an increasingly common scenario. The association between testicular dysgenesis and neoplastic risk is well recognised.
Low birth weight, prematurity, advanced maternal age at delivery, retained placenta. In clinical practice these factors are rarely elicitable from young patients' history.
The fundamental distinction is between germ cell tumours (malignant, oncologically relevant) and non-germ cell tumours (almost always benign).
Large-cell, homogeneous germ cell tumour. Peak incidence around 20 years of age. High radiosensitivity and chemosensitivity. Excellent prognosis.
Heterogeneous group: embryonal carcinoma, yolk sac tumour, choriocarcinoma, teratoma, mixed forms. Peak incidence around 30 years of age.
Leydig cell tumours, Sertoli cell tumours. Almost always benign. Not oncologically relevant, but important for differential diagnosis.
Seminomas ~20 years, non-seminomas ~30 years. The goal is to minimise side effects over a very long remaining life.
Allows choosing the minimum effective treatment rather than maximising therapy.
AFP and Ξ²-HCG have no diagnostic value, but are prognostic: elevated levels = more advanced disease, worse prognosis.
Predictable and constant, thanks to the retroperitoneal origin of the testis. Allows anticipation of disease sites.
Produced in non-seminomas (yolk sac tumour, embryonal carcinoma). Not produced in pure seminomas β if AFP is elevated in a "seminoma", suspect a non-seminomatous component.
Produced in 100% of choriocarcinomas, in 40β60% of embryonal carcinomas, and in a proportion of seminomas with choriocarcinoma islands.
A third marker, LDH (lactate dehydrogenase), is used in combination but is less sensitive and specific than the first two.
The testes originate from the retroperitoneum adjacent to the renal crests: the primary lymph node drainage stations are therefore retroperitoneal, not inguinal (unless scrotal violation has occurred).
In most cases it is the patient himself, or his partner, who discovers a painless swelling of the testis. The swelling is of the testis (didymus), not the epididymis β this is the cardinal clinical finding.
Fundamental distinction on palpation: epididymal swellings are almost always infective-inflammatory processes (epididymitis). Swellings of the testicular body must raise suspicion of neoplasia.
Scrotal mass, generally painless and monosymptomatic. Rarely is diagnosis made through metastatic symptoms.
First-line investigation. The neoplastic lesion is: (a) solid β fluid-containing lesions are almost always benign; (b) vascularised on Doppler. MRI may supplement in selected cases.
Mandatory pre-operative measurement. Not diagnostic, but essential as a prognostic baseline and for post-operative monitoring.
Performed after histological diagnosis. For small nodules (<1 cm) β probable benign neoplasm β may be performed after frozen section. For large masses (β₯3 cm), probability of carcinoma is almost certain: CT may precede surgery.
Before any treatment, in all patients. Surgery and chemotherapy may impact future seminal quality. These are young men who in the majority of cases have not yet had children.
The standard treatment is removal of the testis and spermatic cord. The approach must always be inguinal, never scrotal.
Technique: isolation of the spermatic cord at the internal inguinal ring β extraction of the gonad β ligation of vessels as proximally as possible β orchiectomy without opening the tunica vaginalis if the neoplasm is macroscopically obvious.
Indicated for small nodules β particularly those found incidentally during infertility work-up β and in patients with a solitary testis. Rationale: lesions <1 cm are benign in 75% of cases; radical orchiectomy would be overtreatment in 3 out of 4 patients.
Technique: exploratory inguinotomy β intraoperative ultrasound to localise the lesion β incision of the tunica albuginea over the nodule β nodule excision β frozen section (30β60 min) + definitive histological examination. The albuginea is closed during the waiting period.
The testis is replaced in situ. The patient goes home with the gonad preserved. Probability of parenchymal preservation: >90% for lesions <1 cm.
Immediate radical orchiectomy proceeds. The conservative approach was not futile: without it, the gonad would have been removed in 75% of cases inappropriately.
Testis-sparing surgery preserves a portion of testosterone-producing parenchyma. After radical orchiectomy, testosterone deficiency can affect up to 30% of patients at one year (using a cut-off of 12 nmol/L). Preservation of 1/3β1/2 of functioning testicular tissue significantly reduces this risk.
Treatment depends on the histological subtype (seminoma vs non-seminoma) and the stage (absence/presence of retroperitoneal lymphadenopathy on CT).
Two options: active surveillance (preferred if the patient is motivated and risk factors are absent) or 1β2 cycles of carboplatin (if rete testis invasion or diameter >4 cm). Radiotherapy is not indicated due to long-term side effects in this young population.
3β4 cycles of BEP (Bleomycin + Etoposide + Platinum). High efficacy, low toxicity in young patients. Radiotherapy is not indicated in this setting.
If no lymphovascular invasion: active surveillance. If lymphovascular invasion is present: 1 cycle of BEP. Very rare exception: pure teratoma in the testis with pure teratoma in the retroperitoneum β immediate surgery (teratoma does not respond to radio/chemotherapy).
3β4 cycles of BEP. All retroperitoneal surgery β when indicated β is performed after chemotherapy and only when markers have normalised.
The BEP regimen (Bleomycin, Etoposide, Platinum) is the reference first-line chemotherapy: highly effective in this population. The problem is that second-line chemotherapy for refractory relapses is far less effective β patients with viable carcinoma remaining after BEP are those who die.
Threshold: 3 cm. Masses <3 cm are surveilled. Masses >3 cm require FDG-PET: if no uptake β surveillance; if uptake β surgery of the residual mass (technically demanding due to dense fibrotic tissue surrounding the great vessels).
Threshold: 1 cm. Masses <1 cm are surveilled. Masses >1 cm are always surgically resected (retroperitoneal lymphadenectomy), because the histological content is unpredictable:
The patient is cured. Surgery is unnecessary but unavoidable because the content cannot be predicted before surgery.
Surgery is the only possible treatment (does not respond to radio/chemotherapy). If not resected, it will grow and transform into teratocarcinoma.
Surgery has diagnostic value only. Treatment is second-line chemotherapy β prognosis is severe.
If the retroperitoneum contains teratoma, supradiaphragmatic sites (mediastinum, lungs, lateral cervical lymph nodes) will presumably also contain teratoma. The approach is systemic: resection of all visible masses, including prosthetic replacement of the aorta and inferior vena cava when necessary.