Elsevier

The Lancet Oncology

Volume 4, Issue 12, December 2003, Pages 730-737
The Lancet Oncology

Review
Part I: Testicular cancer—management of early disease

https://doi.org/10.1016/S1470-2045(03)01278-6Get rights and content

Summary

For patients diagnosed with early-stage testicular cancer radical orchidectomy is the primary therapeutic intervention. The major pathological types of testicular cancer are seminoma and non-seminomatous germcell cancer. After orchidectomy, most patients with seminoma receive adjuvant radiotherapy as standard of care, although surveillance and adjuvant chemotherapy protocols are being developed. For patients with non-seminomatous tumours there are three therapeutic options; surveillance, adjuvant chemotherapy, or retroperitoneal lymph-node dissection. These patients are classified into groups with high-risk or low-risk of recurrence by presence of vascular invasion in the surgical specimen. After orchidectomy, about 50% of patients with high-risk disease will relapse but this risk is reduced to less than 5% with adjuvant therapy. Surveillance of patients with low-risk disease is acceptable because testicular cancer is still curable if metastatic recurrence occurs. There is no consensus about the management of early non-seminomatous testicular cancer because survival is almost 100% irrespective of the initial treatment decision.

Section snippets

Histology and biology

Histological classification divides testicular germ-cell tumours into two major subgroups: seminoma and non-seminomatous tumours (figure 2). Both these forms of germ-cell tumour are derived from a progenitor carcinoma in situ (CIS). How transformation from this premalignant condition occurs is controversial and has been the subject of several reviews.1, 2 However, the median time to progression from CIS to malignant disease seems to be about 5 years.

Pure seminomatous histology accounts for

Staging of germ-cell tumours

The clinical stage determined at diagnosis depends on the accuracy of the imaging technique used. In most cases the testicle is the primary site, although tumours can also originate in the retroperitoneum and the mediastinum. Conventional imaging involves CT of the chest, abdomen, and pelvis, which is prone to false positive and negative results. MRI offers equivalent (if not better) accuracy in imaging the abdomen and pelvis and is indicated when a patient is unable to have intravenous

Primary therapy

Most patients with stage I disease present with a testicular mass. Subsequent ultrasound is generally highly diagnostic for a testicular tumour and the patient commonly has an inguinal orchidectomy to enable a detailed pathological analysis. Patients should be offered the option of a prosthetic testicle at this stage and also be considered for a contralateral testicular biopsy.

Contralateral testicular biopsy

A substantial number of studies have addressed the need for contralateral testicular biopsy. About 5% of patients with

Retroperitoneal-lymph-node dissection

RPLND after orchidectomy has been a therapeutic option for patients with stage 1 non-seminomatous germ-cell tumours for several years in the USA. The main supporting argument for this approach is that current radiological techniques inadequately evaluate patients so about 30% of patients diagnosed with stage I disease on the basis of CT are subsequently found to have involved retroperitoneal lymph-nodes at surgery.31 In patients that are found to have positive lymph nodes, and are therefore

Seminoma

About 15–20% of clinical stage I seminomas will relapse after orchidectomy if not given any further treatment. This can be reduced to less than 5% with adjuvant radiotherapy because seminomas are very radiosensitive. Most patients that do relapse can be cured with conventional doses of cytotoxic chemotherapy. There is yet again a therapeutic dilemma about whether adjuvant treatment should be considered after orchidectomy or a surveillance protocol should be adopted. RPLND is not generally used

Radiotherapy

Historically, stage I seminoma has been managed with irradiation of the para-aortic and ipsilateral iliac lymph nodes ("dogleg” field) which results in 98–99% 5-year survival. However, this field of treatment produces significant acute gastrointestinal toxic effects, which are chronic in some patients. In addition, there is an increased risk of second malignancies including primaries in the upper gastrointestinal tract and bladder, and leukaemia, and also reduced fertility in the remaining

Chemotherapy

Carboplatin has activity in metastatic seminoma and when given at low doses is generally associated with very manageable toxicity.40, 41 Several studies have explored its use in the adjuvant treatment of stage I seminoma. Looking at two courses of carboplatin (400mg/m2), Steiner and colleagues recorded two relapses in 108 patients with a median follow up of 59·8 months, Reiter and colleagues reported no tumour-related deaths or recurrences in 107 patients with a median follow up of 74 months,

Surveillance

As with non-seminomatous tumours, the ability to cure recurrent seminoma has facilitated the development of surveillance protocols for stage I disease. Warde and colleagues compared adjuvant radiotherapy with surveillance and found no difference in the cause-specific 5-year survival rate; 100% vs 99·8%.45 Similar results have been observed in several other studies.46, 47, 48 These results, and the fact that 80% of all patients with seminoma are cured by orchidectomy alone, are the main

PET analysis in early germ-cell tumours

PET has the potential to complement conventional CT and better define patients who require additional therapy after orchidectomy. 18F-fluoro-2-deoxy-D-glucose PET highlights differences in glucose metabolism between tumour cells and normal tissues. PET can potentially detect abnormal uptake at metastatic sites not seen on CT and thus a subgroup of patients currently regarded as stage I would actually be considered as stage II. Studies have only involved relatively small numbers of patients and

Follow-up

Follow-up strategies after orchidectomy vary according to whether any form of adjuvant treatment has been given. Specific issues relate to frequency of clinic visits, types of follow-up investigations, and management of the contralateral testis. Some very general principles exist such as the inclusion of chest x-rays and tumour markers at clinic visits but specific follow-up plans vary between institutions and are still under investigation.22

One important issue is the frequency required for

Conclusion

In this review we focused on management issues in early testicular cancer. Almost all patients are cured of their disease but there are differences in the approach taken. The most important criteria for management decisions after orchidectomy is the differentiation in histology between seminoma and non-seminomatous tumours. For non-seminoma, there are arguments for pursuing surveillance, adjuvant chemotherapy, and RPLND. Some guidance can be derived from histological analysis of the

Search strategy and selection criteria

Data for this review were identified by searches of MEDLINE, Current Contents, and PubMed with the search terms “seminoma”, “teratoma”, “NSGCT”, “surveillance”, “adjuvant chemotherapy”, “radiotherapy”, “RPLND”, and “PET”. References from relevant papers were selected as well as abstracts from the Proceedings of the American Society of Clinical Oncology and the European Society of Medical Oncology meetings from 1998 to 2003. Only papers published in English were included but no limits were

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