Controversies in the Management of Stage I Seminoma
Controversies in the Management of Stage I Seminoma
Stage I seminoma is one of the most curable malignancies occurring in men. The overall cause-specific survival approximated 100% in the last decade.
The approach to the management of stages I seminoma changed little between the 1950s and the mid-80s, when effective systemic therapy for metastatic seminoma was introduced. With improvements in the imaging of the retroperitoneum and the availability of effective salvage treatment, the use of routine postorchiectomy adjuvant radiation therapy has been questioned. Surveillance studies disclosed that the majority of patients with stage I seminoma can be cured with orchiectomy alone and that many now receive unnecessary adjuvant therapy.
The overall risk of occult metastatic disease appears to be approximately 15%. Currently, we are unable to accurately identify patients at high risk of occult metastatic disease. Prognostic factors for progression in patients on surveillance programs include the size of the primary tumor, rete testes invasion, young age, vascular and lymphatic invasion, and anaplasia. However, even patients who have several adverse prognostic factors are only at moderate risk of progression, ie, no more than 30%.
The conventional end points used to assess the efficacy of cancer treatment include overall survival, risk of relapse, and treatment toxicity. All of these have been well defined in patients with stage I seminoma treated with adjuvant radiation therapy. Currently, these end points are being defined for patients on surveillance protocols and for those being treated with adjuvant single-agent chemotherapy.
Assessing Long-Term Sequelae of Treatment Options
The authors discuss all of the potential strategies for the management of stage I seminoma, including classical adjuvant para-aortic and pelvic radiation therapy, radiation therapy to para-aortic lymph nodes alone, reduced-dose radiation therapy, surveillance, and adjuvant chemotherapy. Of these, adjuvant chemotherapy, with its extremely low failure rate, minimal toxicity, low cost, and convenience to patients, appears to be the most appealing to young men in the midst of career and family growth and development. However, prior to its adoption as a standard treatment, we need to ascertain that a short course of carboplatin (Paraplatin) chemotherapy does not lead to a later chemoresistant relapse or result in long-term deleterious effects.
Surveillance is another safe and appealing treatment strategy that allows the majority of patients to be cured without adjuvant therapy. When examining the cost-efficacy of surveillance programs, the ultimate cost of managing second cancers, which are potentially induced by the routine use of adjuvant therapy, should be taken into account. This is not possible at present since surveillance protocols are still in the developmental stage.
It is likely that within the next decade, the routine use of postoperative radiation treatment will be abandoned in favor of a treatment preferred by the patient. In 1997, Travis et al reported the results of a large study of second cancers following the treatment of testis tumors. Data from this cohort of 27,000 patients treated at several large cancer registries clearly showed an excess of second cancers in patients with testicular tumors treated with radiation. There is little doubt that, with prolonged follow-up, even low-dose radiation therapy results in an excess risk of second cancer. However, the relative risk of radiation-induced cancer is very low, and patients may choose postoperative radiation therapy because of particular immediate personal or family circumstances.
Risks of Reducing Radiation Dose
We should be cautious about recommending radiation dose reduction because of the low overall prevalence of occult metastatic disease in the retroperitoneum. Only very large trials can exclude a significant increase in the relapse rate with altered radiotherapy protocols. Although the Medical Research Council (MRC) trial comparing para-aortic and pelvic irradiation to para-aortic irradiation alone did not show a statistically significant increase in the risk of relapse when pelvic irradiation was omitted, the statistical power of this study is rather limited. In a disease that has a 5% rate of relapse, a 2% to 7% increase in the relapse rate translates into a 40% increase in the risk of relapse. Therefore, modifications of both radiation fields are unlikely to have a major impact on the management of stage I seminoma.
Management of Testicular Intraepithelial Neoplasia
Another issue in stage I seminoma, which is not discussed by the authors, is the management of testicular intraepithelial neoplasia (testicular carcinoma in situ [CIS]) in the contralateral testis. This issue has been largely ignored in North America. European studies indicate a small, but significant, risk of contralateral CIS and document its role in the development of second testicular tumors.
Although second testicular tumors can be successfully managed, they may lead to a second orchiectomy, culminating in castration in young men. Hormone replacement therapy results in a poor quality of life for young men, and, thus, strategies to preserve testicular endocrine function should be investigated. These strategies include routine testing for contralateral CIS, which, when identified, can be treated with radiation. Low-dose radiation (16 to 20 Gy) has been shown to eradicate testicular CIS while preserving hormonal function. Alternatively, a small or second testicular tumor can be treated with partial orchiectomy and low-dose adjuvant radiation therapy to the scrotum.
Stage I testicular seminoma is an almost universally curable condition. This disease occurs in young men and has a serious impact on quality of life, from both the medical and socioeconomic points of view. The usual end points of cancer treatment are becoming less relevant in this disease. Newer end points of quality of life, preservation of sexual function, preservation of normal hormone status, socioeconomic, and other quality-of-life parameters should be investigated in conjunction with the standard traditional end points of acute and late toxicity, relapse, and survival.
1. Travis LB, Curtis RE, Storm H, et al: Risk of second malignant neoplasms among long-term survivors of testicular cancer. J Natl Cancer Inst 89:19, 1997.
2. Fossa SD, Horwich A, Russel JM, et al: Optimal field size in adjuvant treatment of stage I seminoma. Eur J Cancer 31A(suppl 5):S188, 1995.
3. Giwercman A, Skakkebaek N: Carcinoma in situ of the testis: Biology, screening, and management. Eur Urol 23(suppl 2):19-21, 1993.