Cancer Research UK : Testicular cancer symptoms and treatment

Testicular cancer symptoms and treatment

This page presents information on the symptoms and treatment of testicular cancer.

Testicular cancer symptoms

The most common symptom of germ-cell tumours(GCT) is a painless lump or swelling on one of the testicles, usually noticed by the patient. Other warning signals include enlargement of a testicle, an increase in testicular firmness, pain in a testicle, an unusual difference between one testicle and the other, an ache in the lower stomach or groin and heaviness in the scrotum. Rarely patients may present with the symptoms of advanced disease, which include breast tenderness, back pain, shortness of breath and haemoptysis (coughing up blood).

Testicular cancer treatment

Two important advances have changed the treatment of testicular cancer. Firstly, the discovery of two serum markers, human chorionic gonadotrophin (HCG) and alpha fetoprotein (AFP) during the late 1960s. Both have proved to be reliable indicators of tumour burden within the body and of response to treatment. Secondly, combination chemotherapy, used since 1970 – at first without cisplatin and since the mid-1970s with cisplatin – has proved highly successful as a treatment tool even in patients with metastatic disease.

Testicular cancers are curable in the great majority of cases. Curative treatment varies by type of tumour and the stage of disease at diagnosis.

Treatment guidelines 1-6 and reviews of the management of testicular cancer have been published.7-9 As most patients can be successfully treated, the emphasis of clinical research has shifted to finding ways to minimise treatment-related toxicity (which may increase risk of second cancers,10 cardiovascular morbidity and reduced fertility7, 11) for low-risk patients.

For the small number of patients who are not cured, novel treatments are being investigated.9,12 Research has shown that better outcomes are achieved in larger rather than smaller treatment centres.13,14

Treatment of Seminoma testicular cancer

Seminomas are more radiosensitive and more chemosensitive than nonseminomas and survival rates have always been high. Seminoma patients also tend to present with earlier stage disease than those with nonseminoma (Figure 6.1).

Figure 6.1: Proportion of patients with stages of seminoma and non-seminoma and survival rates (1974-2003)

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Approximately 80% of seminoma patients present with early disease. For many years the standard treatment for seminoma in the UK has been surgery (inguinal orchidectomy) followed by adjuvant radiotherapy.7 Following clinical trials, both the radiation field and the amount of radiation needed were reduced to minimise long-term effects.15,16 Excellent survival rates of 95–100% are achieved with minimal morbidity.

A randomised trial has shown that surgery followed by a single cycle of carboplatin is equivalent to surgery followed by radiotherapy in reducing the risk of recurrence of testicular caancer, and has lower toxicity. Concerns about the long term toxicity of radiotherapy (see above) have led recently to adoption of surgery plus carboplatin as the standard treatment for seminomas in the UK.17,18 Patients with stage I disease have an approximately 20% chance of relapse with surgery and no further treatment, which has led to an increase in popularity of managing testicular cancer in these patients with surveillance.

Risk of relapse is higher (around 32%) if tumour size is >4cm and there is evidence of rete testis (the rete testis is a network of tubules in the centre of the testis) invasion (risk is reduced if only one of these factors is present).19 More advanced disease and disease recurrence can be treated effectively with combination chemotherapy.

Between a third and a half of nonseminoma patients have early disease when first treated and again inguinal orchidectomy is the main treatment. Larger UK centres divide clinical stage I cases into low- and high-risk according to the presence or absence of vascular invasion. Following surgery, low-risk patients are managed with surveillance, while high-risk patients receive either adjuvant chemotherapy or undergo surveillance. This results in cure rates of 99%.20

A trial of functional imaging showed that positron emission tomography (PET) scanning had only marginal effect on diagnostic accuracy.21

More advanced nonseminoma patients are treated with chemotherapy. Usually this is with a schedule called BEP (consisting of three drugs, bleomycin, etoposide and cisplatin). Surgery is used to remove any post-treatment masses. Outcome of treatment can be predicted by a prognostic index (Figure 6.2) based on the level of tumour markers, site of primary tumour and the presence or absence of nonpulmonary metastases.22,23

Figure 6.2: Ten-year actuarial survival for patients with disseminated nonseminomatous testicular germ cell tumours (IGCCCG classification)

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Between 1987 and 1996, around 50% of all nonseminoma patients were categorised in the good prognosis group. For this group, ten-year survival rates are over 90%.

A further third of patients fall into the intermediate prognosis group, which has ten-year survival rates of 87%. The largest increase in survival has been for the poor prognosis group. For those diagnosed between 1977 and 1986, ten-year survival rates were 37%. This rate has risen to 66% for patients diagnosed between 1987 and 1996.

24 High-dose chemotherapy with autologous bone marrow or peripheral blood stem-cell transplantation has been tested in an attempt to improve survival of patients relapsing after initial treatment. However this treatment did not improve survival compared to standard treatment25 so it is generally now reserved for carefully selected patients in second relapse.7,26

Contralateral testicular cancer

In a very small percentage (5%) of patients, the contralateral testis shows signs of CIS which would be expected to progress to carcinoma in the majority of cases. Because of this low risk and the attendant morbidity associated with testicular biopsy, there is not yet a consensus on whether to screen the contralateral testis in all cases. 2, 8 Options need to be discussed with the patient.

The future of testicular cancer treatment

During the last 40 years, testicular cancer has become a curable malignancy in over 95% of patients (Figure 6.3). This success has led to a new emphasis on decreasing the side effects of treatment and improving patients’ quality of life, both during and after treatment.16, 27-31

Figure 6.3: Age-standardised (European) incidence and mortality rates for testicular cancer, Great Britain, 1975-2005

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For patients with metastatic disease that cannot be cured using current treatments, more effective therapies are being developed and tested.12, 32,33 As there is a clear association between delay in diagnosis and more advanced disease,34 it is important to improve and extend health education so that fewer patients present with metastatic disease.35 Recent data from London has shown that this is already occurring, but further improvements could be made.36

At present, three groups of risk factors stand out. Firstly, those acting in utero during foetal gonadal development; secondly, post-pubertal factors and thirdly, genetic factors. Understanding the interplay between these risk factors will be essential for a full understanding of the aetiology of germ cell testicular tumours.

References for testicular cancer symptoms and treatment

Clinical Oncology Information Network (COIN), Guidelines on the management of adult testicular germ cell tumours. Clin Oncol12(Suppl): S173-210, 2000.
Albers P et al, Guidelines on Testicular Cancer. European Association of Urology, 2006
NICE, Guidance on Cancer Services. Improving Outcome in Urological Cancers. 2002, National Institute for Clinical Excellence.
Schmoll, H.J., et al., European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG). Ann Oncol, 2004. 15(9): p. 1377-99
Huddart, R.A. and G. Purkalne, ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of mixed or non-seminomatous germ cell tumors (NSGCT). Ann Oncol, 2005. 16 Suppl 1: p. i37-9.
Huddart, R.A. and V.V. Kataja, ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of testicular seminoma. Ann Oncol, 2005. 16 Suppl 1: p. i40-2.
Horwich, A., J. Shipley, and R. Huddart, Testicular germ-cell cancer. The Lancet, 2006. 367(9512): p. 754.
Jones, R.H. and P.A. Vasey, Part I: testicular cancer--management of early disease. Lancet Oncol, 2003. 4(12): p. 730-7.
Jones, R.H. and P.A. Vasey, Part II: testicular cancer--management of advanced disease. Lancet Oncol, 2003. 4(12): p. 738-47.
Travis, L.B., et al., Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst, 2005. 97(18): p. 1354-65.
Huddart, R.A., et al., Cardiovascular disease as a long-term complication of treatment for testicular cancer. J Clin Oncol, 2003. 21(8): p. 1513-23.
Kollmannsberger, C., C. Nichols, and C. Bokemeyer, Recent advances in management of patients with platinum-refractory testicular germ cell tumors. Cancer, 2006. 106(6): p. 1217-26.
Harding, M.J., et al., Management of malignant teratoma: does referral to a specialist unit matter? Lancet, 1993. 341(8851): p. 999-1002.
Collette, L., et al., Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party. J Natl Cancer Inst, 1999. 91(10): p. 839-46.
Fossa, S.D., et al., Optimal planning target volume for stage I testicular seminoma: A Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group. J Clin Oncol, 1999. 17(4): p. 1146.
Jones, W.G., et al., Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I Testicular Seminoma: a report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J Clin Oncol, 2005. 23(6): p. 1200-8.
Oliver, R.T., et al., Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet, 2005. 366(9482): p. 293-300.
Huddart, R.A. and J.K. Joffe, Preferred treatment for stage I seminoma: a survey of Canadian radiation oncologists. Clin Oncol (R Coll Radiol), 2006. 18(9): p. 693-5.
Warde, P., et al., Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol, 2002. 20(22): p. 4448-52.
Cullen, M.H., et al., Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: a Medical Research Council report. J Clin Oncol, 1996. 14(4): p. 1106-13.
Huddart, R., et al., A prospective study of 18FDG PET in the prediction of relapse in patients with high risk clinical stage I (CS1) non-seminomatous germ cell cancer (NSGCT): MRC study TE22. J Clin Oncol (Meeting Abstracts), 2006. 24(18_suppl): p. 4520
Sonneveld, D.J., et al., Improved long term survival of patients with metastatic nonseminomatous testicular germ cell carcinoma in relation to prognostic classification systems during the cisplatin era. Cancer, 2001. 91(7): p. 1304-15.
International Germ Cell Cancer Collaborative Group.International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol, 1997. 15(2): p. 594-603.
de Wit, R., et al., Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol, 2001. 19(6): p. 1629-40.
Pico, J.L., et al., A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol, 2005. 16(7): p. 1152-9.
Beyer, J., et al., J Clin Oncol, 1996. 14(10): p. 2638-45.

Dearnaley, D.P., et al., Adjuvant bleomycin, vincristine and cisplatin (BOP) for high-risk stage I non-seminomatous germ cell tumours: a prospective trial (MRC TE17). Br J Cancer, 2005. 92(12): p. 2107-13.
Oliver, R.T., et al., Long-term follow-up of Anglian Germ Cell Cancer Group surveillance versus patients with Stage 1 nonseminoma treated with adjuvant chemotherapy. Urology, 2004. 63(3): p. 556-61.
Atsu, N., et al., A novel surveillance protocol for stage I nonseminomatous germ cell testicular tumours. BJU Int, 2003. 92(1): p. 32-5.
Hellerstedt, B.A. and K.J. Pienta, Germ cell tumors: review of selected studies from 2002. Curr Opin Oncol, 2003. 15(3): p. 234-8.
Heidenreich, A., Clinical stage I nonseminomatous testicular germ-cell tumors: surgery or watchful waiting, still an issue? Curr Opin Urol, 2002. 12(5): p. 427-30.
Kondagunta, G.V., et al., Etoposide and cisplatin chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol, 2005. 23(36): p. 9290-4.
Fossa, S.D., et al., Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer, 2005. 93(11): p. 1209-14.
Prognostic factors in advanced non-seminomatous germ-cell testicular tumours: results of a multicentre study. Report from the Medical Research Council Working Party on Testicular Tumours. Lancet, 1985. 1(8419): p. 8-11.
Steele, J.P. and R.T. Oliver, Testicular cancer: perils of very late presentation.Lancet, 2002. 359(9318): p. 1632-3.
Bhardwa, J.M., et al., Assessing the size and stage of testicular germ cell tumours: 1984-2003. BJU Int, 2005. 96(6): p. 819-21.

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