Radiotherapy versus carboplatin for stage I seminoma: Updated analysis of the MRC/EORTC randomized trial Authors: Oliver et al, ASCO Abstract: 1 Date posted: July 2008

BACKGROUND Stage I seminoma is the most common testicular cancer presentation Treatment options: Radiation therapy:  4% relapse rate Surveillance:  15-20% relapse rate Chemotherapy with Carboplatin Cure rate should be  99% Case series suggest Carboplatin x 1 is as good as RT

Treatment A: Carboplatin x 1 7 x (GFR + 25) by EDTA or creatinine clearance (not Cockcroft) Treatment B: Radiotherapy Gy Stage I Seminoma Randomization 3C:5RT

DESIGN Non-inferiority Powered to exclude an increase in 2 year relapse rate of  3% with chemotherapy Accrual: Planned accrual n=1200 Actual accrual n=1447 First presented ASCO 2004 and published Lancet 2005;366:293 Updated analyses planned 5 years after last patient entry Median follow-up = 6.5 years 78% with follow-up  5 years

TOXICITY CarboRTp-value AllGrade 3/4AllGrade 3/4 Thrombocytopenia21%9%2%0%  Dyspepsia8%17%  Unable to Work – Week 4 19%38%  – Week 12 10%14%NS

Results CarboRTp-value n Total Relapses29 (5%)37 (4%) New Primary7 (1.1%)25 (2.8%) – GCT 2 (0.3%)15 (1.7%) – Other 5 (0.8%)10 (1.1%) Total Deaths6 (1.0%)10 (1.1%) – From Seminoma 01 5y Relapse-free94.7% ( )96% ( )0.37

STUDY COMMENTARY Carboplatin x1 (AUC of 7) is safe and is not inferior to radiation for stage I seminoma with relapse rate of 5.3% (RT=4%) Carboplatin dosing is important and need an AUC  7 Will take  20 years to determine the cardiovascular toxicity and secondary malignancy rates with this treatment Still remains to be seen whether Carboplatin x1 simply delays the relapse vs. prevents it – longer follow-up than 6.5 years may be needed

BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS Stage I seminoma treatment options include surveillance, Carboplatin and radiation Carboplatin and RT over-treat 80% of patients Carboplatin and RT still require long-term follow-up including CT scan imaging Carboplatin may have cardiovascular morbidity Therefore, surveillance makes the most sense for the majority of men after a full discussion has taken place If treatment wanted/needed, the: Known short-term and long-term risks of radiation Known short-term and unknown long-term risks of Carboplatin need to be discussed with patients