The efficacy of radiotherapy in treating clinical stage I seminoma has been reported in numerous series, with a 5-year progression-free survival of over 95% and nearly all relapses occurring outside the radiation field. Short-term toxicities are usually mild, with nausea and vomiting, diarrhea, fatigue, and skin erythema being the most common. However, the long-term cost to patients is only now being fully understood. The risk of a second malignancy doubles in these patients, compared with the general population. The risk of a solid cancer is between 5% and 10%, and the absolute risk is about twice that seen in the general population. This translates into an additional six to nine cancers over the 25 years after treatment for every 100 men treated. These malignancies are usually confined to the area of irradiation such as the bladder, kidney, skin, and stomach, but prostate, lung, and head and neck cancers have been reported outside those fields, likely secondatry to radiation scatter.[10-14,29]
Furthermore, radiotherapy is associated with cardiotoxicity in the long term, also due to radiation scatter and not direct damage, because irradiated areas are below the diaphragm.[24,30] Both factors contribute to a decreased survival compared to other men in the general population.
In recognition of these effects, radiotherapy fields have been modified from the pre-1990 model of anteriorly and posteriorly delivered so called “dogleg” fields that covered lymphatic drainage of the testis to include the ipsilateral pelvis and the para-aortic region. This has not resulted in a reduction in survival rates, but isolated cases of recurrence at the edge of traditional fields have been surfacing in the literature.[28,31-34] The reduction of overall treatment doses is also being explored but reductions beyond 30 and 20 Gy have yet to be published. Any reduction in overall dose is thought to reduce the late radiation effects, as is reducing the daily dose fraction from 2 to 1.5 Gy. Risks to fertility remain despite shielding of the contralateral testis. They may be related to the disease process itself, and not just the treatment.[23,36]
The rationale for chemotherapy was borne out of concern with the secondary effects of radiotherapy as well as with the recognition that where tumors are sensitive to chemotherapy, reduced doses have often been successful. Carboplatin has emerged as a primary adjuvant treatment alternative for stage I seminoma based on the use of combination chemotherapy for higher-stage germ cell tumors. The short-term toxicities from single- or dual-dose chemotherapy for seminoma are minimal but include gastrointestinal side effects and fatigue. In the long term, data are unknown and hypothetical, but based on longer-duration courses of chemotherapy for nonseminomatous tumors, the possibilities of cerebrovascular disease, infertility, neuropathy, and leukemia as well as other second malignancies remain. Cardiotoxicity may not be a concern.[22,29,37]
Although the most recent publication concerning a single cycle of carboplatin included only a modest follow-up of 4 years, it proved to be noninferior to radiotherapy in terms of relapse rates and survival. Despite this evidence and guideline recommendations as outlined previously, many authors believe that carboplatin should not be considered the standard of care.[37,38] Others have argued that two courses of treatment are necessary when carboplatin is used.[20,21] Even with two cycles, a small but significant percentage of patients (3%–4%) experience a recurrence in the retroperitoneum.
Stage I seminoma is a highly curable disease but does require some degree of follow-up. The aim of follow-up of testicular cancer patients is twofold: (1) to detect relapses early when minimal disease is present so that they may be salvaged, and (2) to detect and manage the effects of the original definitive oncologic treatment.
A major criticism of active surveillance is that the required number of follow-up investigations brings on anxiety that reduces quality of life. In addition, the multiple follow-up visits increase health-care costs. That said, it is worth noting that the 2009 NCCN guidelines recommend the same imaging and follow-up whether a man is treated with surveillance or chemotherapy. Among men who have undergone radiation therapy, imaging of the retroperitoneum is not required due to the reduced risk of recurrence.
Similar to the treatment paradigm, a non–evidence-based, risk-adapted follow-up strategy has been recommended.[39,40] Studies are currently underway to reduce the use of computed tomography in surveillance of testicular tumors such that more limited protocols may be developed, thus reducing potential risk of radiation.
Quality-adjusted life-year (QALY) assessments show a similar result—around 20—for all three modalities, but the cost per QALY is greater for surveillance and similar for radiation and chemotherapy. Surveillance regimens are likely to be reduced in the coming years, altering the cost of surveillance and leaving only toxicities and overtreatment as issues to consider.
In conclusion, we believe that if a patient is willing and able to comply with a surveillance policy, then long-term close follow-up should be recommended after orchiectomy for clinical stage I seminoma. This is because radiotherapy and chemotherapy will overtreat > 80% of patients, with the possibility of acute and late toxicities, while surveillance patients have the same ultimate cure rate. Long-term data on survival and toxicities of chemotherapy are not yet available for large numbers of patients. However, each center must factor in staff experience, costs, compliance, psychosocial issues, and the impact on fertility for any individual patient prior to selecting a treatment.
The future may yield risk-adapted strategies not only for providing details on prognosis and giving information for selecting the appropriate adjuvant treatment, but also to help minimize follow-up in surveillance patients and reduce costs to the community.
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.
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