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Radiotherapy versus carboplatin for stage I seminoma: Updated analysis of the

MRC/EORTC randomized trial

Authors: Oliver et al, ASCO 2008.

Abstract: 1

Date posted: July 2008

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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

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Treatment A:

Carboplatin x 17 x (GFR + 25) by EDTA or creatinine clearance(not Cockcroft)

Treatment B:

Radiotherapy20-30 Gy

Stage I Seminoma

Randomization 3C:5RT

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DESIGN

• Non-inferiority

• Powered to exclude an increase in 2 year relapse rate of 3% with chemotherapy

• Accrual: 1996-2001

• 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

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TOXICITY

Carbo RT p-value

All Grade 3/4 All Grade 3/4

Thrombocytopenia 21% 9% 2% 0% 0.001

Dyspepsia 8% 17% 0.001

Unable to Work

– Week 4 19% 38% 0.001

– Week 12 10% 14% NS

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Results

Carbo RT p-value

n 573 904

Total Relapses 29 (5%) 37 (4%)

New Primary 7 (1.1%) 25 (2.8%)

– GCT 2 (0.3%) 15 (1.7%)

– Other 5 (0.8%) 10 (1.1%)

Total Deaths 6 (1.0%) 10 (1.1%)

– From Seminoma 0 1

5y Relapse-free 94.7% (92.5-96.3) 96% (94.5-97.1) 0.37

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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

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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