Univariate Analyses Treatment Outcome And Patterns Of Relapse Following Adjuvant Carboplatin For Stage I Testicular Seminoma: Results From a 17 Year UK Experience Caroline Chau 1,2,3, Matthew Wheater 3, Richard Cathomas 4, Martin Fehr 5, James Bennett 6,Dirk Klingbiel 7, Hannah Markham 3, Chern Lee 1,3,Simon J. Crabb 1,3, Thomas Geldart 6 1. Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton, UK 2. NIHR Wellcome Trust Clinical Research Facility, University of Southampton, Southampton, UK 3. Department of Medical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK 4. Medical Oncology, Kantonsspital Graubünden, Chur, Switzerland 5. Medical Oncology, Kantonsspital St. Gallen Hospital, St. Gallen, Switzerland 6. Dorset Cancer Centre, Poole Hospital NHS Foundation Trust, Poole, UK 7. Swiss Group for Clinical Cancer Research Coordinating Center Background Conclusions This is the first non-trial series describing the clinical outcome and relapse pattern of patients with stage I seminoma treated with a single cycle of adjuvant carboplatin chemotherapy (AUC 7) dosed using radioisotope measured GFR Our data confirms that routine clinical practice for these patients within the context of a high volume centre is comparable in outcome to prospective trial data Relapse beyond 3 years was rare (0.8%) Tumour size greater than 40mm was associated with a higher rate of relapse Salvage treatment at relapse Aim and Method Patient Characteristics 518 consecutive patients identified Median age at diagnosis 38 years (range 18 – 73). Median follow up was 47.2 months (range 0.4 – 217) 5-year cancer-specific survival is 100% (6 patients died, all deaths unrelated to seminoma) Patterns of relapse Stage I seminoma: The commonest presentation of testicular germ cell tumours (GCT) with excellent prognosis Approximately 80% of patients are cured with orchidectomy alone No prospectively defined risk categories - retrospective series showed tumour size >40mm and rete testis invasion had a significantly higher relapse rate of up to 32% (Warde P et al; JCO 2002) Salvage therapy at relapse is highly effective irrespective of post- ochidectomy strategy Active surveillance (relapse rate of 15 – 20%) Detect relapse early whilst avoiding morbidities and risks of adjuvant treatment Need for intensive follow up and patient compliance is paramount No consensus regarding the optimum surveillance schedule Adjuvant therapy (relapse rate of 4 – 5%) Adjuvant radiotherapy (ART) vs. adjuvant chemotherapy (ACT) TE-19 trial showed non-inferiority of ACT with a single dose of carboplatin (AUC7) compared with ART (RFR at 5 years of 94.7% and 96.0% respectively) (Oliver RT et al, JCO 2005/2011) Carboplatin treated patients were less lethargic and less likely to take time off work after treatment and developed fewer contralateral GCT Aim To provide real world data of clinical outcome and patterns of relapse in patients with stage I seminoma treated with a single dose of adjuvant carboplatin chemotherapy (AUC 7) All patients underwent radioisotope measurement of GFR Method A retrospective study including patients from 3 cancer centres (Southampton, Portsmouth, Dorset) between July 1996 to October 2013 Tumour size ≤40 mm >40mm Unknown 333 (64.3%) 169 (32.6%) 16 (3.1%) Rete testis invasion No Yes Unknown 331 (63.9%) 166 (32.0%) 21 (4.1%) >40mm and rete testis invasion No Yes Unknown 427 (82.4%) 65 (12.5%) 26 (5.0%) Time to adjuvant carboplatin (days) ≤ >60 Unknown 103 (19.9%) 284 (54.8%) 112 (21.6%) 19 (3.7%) No. of relapse Relapse rate 5-year RFS p value Tumour size ≤40 mm >40 mm Unknown 11/333 10/169 1/16 3.3% 5.9% 6.3% 95.5% 93.6% 0.05 Rete testis invasion No Yes Unknown 13/331 7/166 2/21 3.9% 2.2% 9.5% 95.1% 94.9% 0.75 >40 mm & rete invasion No Yes Unknown 17/427 3/65 2/19 4.0% 4.6% 7.7% 95.1% 94.0% 0.67 Time to adjuvant carboplatin ≤30 days 31 – 60 days >60 days Unknown 4/103 14/284 3/112 1/19 3.9% 4.9% 2.7% 5.3% 95.4% 93.9% 96.4% Univariate analyses for possible risk factors for relapse 22 patients relapsed (4.2%) Estimated relapse free survival (RFS) 97.3% at 2 years (95% CI 95.8 – 98.7%) 94.8% at 5 years (95% CI 92.6 – 97.1%) Median time to relapse was 22.4 months (range 11 – 108) 82% of relapsing patients did so within the first 3 years. 4 patients (0.8%) relapsed after 3 years (at 49, 50, 53, 108 months) Setting of relapse detection Detected at routine follow up Unplanned 14 (64%) 8 (36%) First indicator of relapse Abdominal CT Elevated tumour markers Other abdominal imaging 16 (72%) 3 (14%) Elevated LDH or β-HCG at relapse Yes No Unknown 17 (77%) 4 (18%) 1 (5%) Site of relapse Retroperitoneal lymph nodes Iliac lymph nodes Multiple nodal sites Multiple nodal + visceral 18 (82%) 1 (4.5%) 2 (9%) 1 (4.5%) IGCCCG risk group at relapse Good prognosis Intermediate prognosis 21 (95%) 1 (5%) Salvage therapy at 1 st relapse Chemotherapy Dogleg radiotherapy 18 (82%) 4 (18%) Salvage chemotherapy regime at 1 st relapse BEP x 3 Modified BEP x 4 BEP x 4 Other 8 (44%) 6 (33%) 1 (6%) 3 (17%) 22 patients relapsed Second relapse 3 cisplatin containing chemotherapy (TIP, EP) 1 radiotherapy Third relapse 1 x4 TIP chemotherapy 18 salvage chemotherapy 4 salvage radiotherapy First relapse 18 alive and disease free 2 alive and disease free 1 dead 1 alive and disease free 518 patients Corresponding author: Dr. Caroline Chau