Adjuvant Bleomycin, Etoposide and Cisplatin (BEP) Versus Carboplatin in Stage I Seminomatous Testicular Cancer
Adjuvant Bleomycin, Etoposide and Cisplatin (BEP) Versus Carboplatin in Stage I Seminomatous Testicular Cancer
One course of adjuvant carboplatin AUC7 is considered internationally to be a standard
 treatment option in clinical stage I seminoma, regardless of risk factors. Treatment is based
 on a large, randomized phase III study comparing adjuvant carboplatin with adjuvant
 radiotherapy. This study was done without registering data on possible risk factor for
 relapse. The relapse rate following carboplatin was in this study estimated to be 5.3 %. Data
 from a prospective, risk-adapted Spanish study showed that patients without risk factors had
 a very low risk of relapse, even without adjuvant treatment. This result is also confirmed by
 a recent analysis of SWENOTECA VII data, showing that this group of patients has a risk of
 relapse of less than 5 % without adjuvant treatment.

 Combined data from SWENOTECA V and VII studies indicate a high risk of relapse in patients
 with one or two risk factors (tumor 4 cm, stromal invasion of rete testis) treated with one
 course of adjuvant carboplatin. The relapse rate in this group of patients was 9.4 %,
 indicating a very modest effect of one course of adjuvant carboplatin. If adjuvant
 chemotherapy is the preferred treatment strategy, more potent chemotherapy regimens should be
 explored in this patient group. The results from SWENOTECA III/VI studies with one course of
 cisplatin-based adjuvant chemotherapy in clinical stage I nonseminoma, show a very low rate
 of relapse. As seminoma is even more chemosensitive than nonseminoma the relapse rate
 following one course of adjuvant BEP is expected to be very low, close to 1 %.

 The overall aim is to investigate whether one course of adjuvant BEP have a lower relapse
 rate than one course of adjuvant carboplatin AUC7. In addition, it will be investigated if
 there is a difference in health related quality of life as well as acute and long-term
 toxicities from treatment.
Short term overall survival is, regardless of treatment allocation, expected to be very close
 to 100 %. The primary outcome is relapse rate. The power of the study depends on the number
 of observed relapses. If the relapse rate in the adjuvant carboplatin group, the reference
 group, is lower than the anticipated 9 %, we need to include more patients to the study.
 Based on all previous published material on adjuvant treatment in clinical stage I seminoma
 it is not possible to precisely estimate the correct relapse rate until the median follow-up
 is four years. Consequently, we will estimate the relapse rate in the reference group close
 to the end of accrual. If the estimated relapse rate, and thus the number of relapses, is
 lower than the anticipated we will increase the sample size to make sure that the study meets
 the minimum required number of relapses in the reference group. A possible inclusion of more
 study participants does not compromise the Type I error rate of the study.
Inclusion Criteria:

 -  Histological diagnosis of unilateral seminoma testicular cancer, evaluating both size
 of tumor and invasion of the rete testis

 -  Clinical stage I

 -  Tumor size over 4 cm and/or stromal invasion of the rete testis by tumor cells

 -  Normal value of alpha-fetoprotein (AFP) before orchiectomy. A stable, slightly
 elevated AFP as a normal value may be permitted.

 -  Age ≥ 18 years and < 60 years

 -  Adequate organ function defined as:

 Serum aspartate transaminase (ALT) ≤ 1.5 x upper limit of normal (ULN). Total serum
 bilirubin ≤ 1.5 x ULN Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L
 Creatinine clearance > 50 ml/min (eGFR) All fertile patients should use safe contraception
 Written informed consent

 Exclusion Criteria:

 -  Signs of metastatic disease evaluated by CT thorax, abdomen and pelvis. Patients in
 need of restaging (see SWENOTECA IX) should not be included

 -  Prior diagnosis of testicular cancer

 -  Chronic pulmonary disorders giving a high risk of bleomycin induced toxicity (for
 example chronic obstructive pulmonary disease or lung fibrosis)

 -  Cancer other than seminoma testicular cancer

 -  Known hypersensitivity or contraindications for the study drugs

 -  Serious concomitant systemic disorders (for example active infection, unstable
 cardiovascular disease) that in the opinion of the investigator would compromise the
 patient's ability to complete the study or interfere with the evaluation of the
 efficacy and safety of the study treatment

 -  Medical, social, psychological conditions that could prevent adequate information and
 follow-up