CME Continuing Medical Education
ONCOLOGY.
No. 9
Areas of Confusion in Oncology
Therapeutic Options Following Orchiectomy for Stage I Seminoma
By Nathan Lawrentschuk, MB BS, FRACS
Uro-oncology Fellow
Neil E. Fleshner, MD, MPH, FRCSC
Head, Division of Urologic Oncology
University of Toronto
University Health Network
Princess Margaret Hospital
Toronto, Ontario, Canada |
August 13, 2009
Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
ABSTRACT: Stage I seminoma represents the paradigm of a curable malignancy, with survival of 100% an expected outcome no matter what treatment option is chosen. However, consensus has not been reached among urologists and oncologists regarding the optimal postoperative management in men with clinical stage I testicular seminoma. Currently, men are offered active surveillance, adjuvant radiation therapy, or single-agent chemotherapy. Active surveillance is associated with an 80% chance of no relapse, with all such events salvageable. Radiotherapy has an almost universal cure rate but has the potential for long-term toxicities and an overtreatment rate of about 80%. Chemotherapy efficacy and toxicity data are still immature. Recent guidelines recognize that the options of surveillance, chemotherapy, and radiotherapy are appropriate in the treatment of patients with clinical stage I seminoma. We believe active surveillance to be the best option, then radiotherapy (considering the efficacy and safety data), with single-agent chemotherapy emerging as a possible alternative.
Over the past 3 decades, the incidence rate of testicular seminoma has continually risen, and the majority of cases have been clinical stage I.[1] Nevertheless, the overall survival for all testicular cancers has improved significantly (P < .05) over the same period, from 83% to 96%.[2] Seminomas generally have a lower stage at diagnosis than nonseminomatous germ cell tumors (NSGCT), are generally less advanced, and are associated with better survival. In fact, stage I seminoma represents the paradigm of a curable malignancy, with survival of 100% an expected outcome no matter what treatment option is chosen. However, consensus has not been reached among urologists and oncologists regarding the postoperative management of men with clinical stage I testicular seminoma.[3] Currently, men are offered active surveillance, adjuvant radiation therapy, or single-agent chemotherapy (Table 1).[4] We will outline the treatment options for clinical stage I seminoma and discuss the controversies surrounding each approach. Background and Risk-Adapted Strategies Over time, radiotherapy has established itself as an appropriate adjuvant treatment for clinical stage I seminoma, which significantly reduces the relapse rate.[5-9] Unfortunately, radiotherapy is associated with a doubling in the risk of developing a second malignancy compared with the general population; although absolute risks remain small.[10-14] Chemotherapy is probably equivalent to radiotherapy in terms of efficacy,[15] but long-term risks are unknown.[16] Active surveillance avoids overtreatment in the vast majority of patients, as only approximately 17% of patients are likely to relapse.[17] Therefore, recommendations for the treatment of clinical stage I seminoma have recently been updated. The overriding theme of recent guidelines is the recognition that the options of surveillance, chemotherapy, and radiotherapy are all appropriate in the treatment of patients with clinical stage I seminoma.[4,18,19] Nevertheless, there are some caveats. For example, in the 2009 National Comprehensive Cancer Network (NCCN) Testicular Cancer Clinical Practice Guidelines, each of these options is rated category 1—that is, there is a uniform consensus among experts regarding their recommendation as approved treatment. In the fine print, however, surveillance is recommended as category 1 only for patients who have undergone previous radiotherapy, who have a horseshoe kidney, or who have inflammatory bowel disease. Surveillance is considered category 2B for others motivated to undergo follow-up and more intensive imaging. Meanwhile, chemotherapy has been raised to equal status with the more traditionally used radiotherapy as NCCN category 1 for all comers. This is despite long-term toxicity data and is based on early data demonstrating equivalent short-term efficacy with radiotherapy, with very few side effects.[15] Medical oncologists believe that along with its demonstrated efficacy, chemotherapy is less burdensome and toxic than radiotherapy, requires minimal hospital contact, reduces anxiety, and results in few reported relapses at just under 10 years’ follow-up. Moreover, salvage chemotherapy remains a viable option even if relapse occurs.[20-22] The most recent European Association of Urology (EAU) guidelines offer similar preferences, with surveillance as a grade B recommendation behind chemotherapy and radiotherapy (category A).[19]
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