MRC TE19: Radiotherapy versus single-dose carboplatin in adjuvant treatment of Stage I Seminoma: a randomised (sic) trial

Author: Oliver RTD et al.
Source: Lancet 366: 293-300.

Background

The standard treatments for stage I seminoma are not ideal. Radiation carries the risk of second malignancy in these young patients, the majority of whom would remain free of disease even without radiation. Surveillance, however, carries its own risks. Some patients are lost to follow-up, and even with close follow-up, some patients will have advanced disease when their recurrence is discovered. This increases the risk of transformation into less curable non-seminomatous malignancies. An alternative treatment option such as carboplatin might alleviate some of these issues.

Methods

• 1477 patients with stage pT1-pT3 seminoma were enrolled from 70 institutions.
• Median follow-up was 4 years, and 91% of patients were followed for > 2 years.
• Patients were randomized after orchiectomy to carboplatin or radiation.
• Carboplatin was dosed 7*(GFR[mL/min]+25)mg.
• Radiation was given in 200 cGy fractions to a final dose of either 20 Gy or 30 Gy. 13% of irradiated patients were treated to a dog-leg field in addition to a para-aortic field.
• Patients were stratified by institution; radiation dose; and history of previous surgery in the pelvis, scrotum, or inguinal area.
• They were assessed for relapse using clinical exam, tumor markers, chest x-ray, and CT of the chest/abdomen/pelvis. CT scanning was performed annually for 3 years.
• The primary endpoint was the relapse-free survival. Secondary endpoints were death from any cause, second malignancy, and morbidity.

Results

The study accrued enough patients to determine a 3% difference in relapse-free survival with 90% certainty. The two arms were well matched with respect to patient characteristics.

Relapse-free survival was not significantly different between the two arms. However, patients who received carboplatin were more likely to recur in the para-aortic nodes, whereas those who received radiation were more likely to recur in the pelvic or supradiaphragmatic nodes.

Second germ-cell tumors occurred significantly more often in the radiation arm.

Acute side effects differed between the two arms. In the carboplatin arm, thrombocytopenia was more common, but dyspepsia was less common.

Discussion

Since relapse rates are identical with either treatment, carboplatin offers several benefits. It may reduce the risk of second germ-cell tumors by sterilizing carcinoma-in-situ present in the remaining gonad. Further, it may have less impact on fertility than radiation would, at least in the case of radiation treatment that includes a dog-leg field.

However, several issues remain to be addressed. Neither the optimal dosing nor the ideal follow-up strategies have been established for carboplatin therapy. In addition, it is possible that relapse rates will diverge with longer follow-up. Thus far, however, it appears that carboplatin is a reasonable adjuvant treatment option for patients with stage I seminoma.