Transcript Slide 1

Treatment Outcome And Patterns Of Relapse Following Adjuvant Carboplatin For Stage I Testicular Seminoma:
Results From a 17 Year UK Experience
Caroline Chau1,2,3, Matthew Wheater3 , Richard Cathomas4, Martin Fehr5, James Bennett6,Dirk Klingbiel7, Hannah Markham3, Chern Lee1,3,Simon J. Crabb1,3, Thomas Geldart6
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
Patient Characteristics
Patterns of relapse
Stage I seminoma:
•
518 consecutive patients identified
22 patients relapsed (4.2%)
•The commonest presentation of testicular germ cell tumours (GCT)
with excellent prognosis
•
•
Median age at diagnosis 38 years (range 18 – 73). Median follow up
was 47.2 months (range 0.4 – 217)
•
•
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%)
5-year cancer-specific survival is 100% (6 patients died, all deaths
unrelated to seminoma)
•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 postochidectomy 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 and Method
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)
≤30
31-60
>60
Unknown
103 (19.9%)
284 (54.8%)
112 (21.6%)
19 (3.7%)
Univariate Analyses
Univariate analyses for possible risk factors for relapse
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%
0.59
0.63
518 patients
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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%)
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
Salvage therapy at 1st relapse
Chemotherapy
Dogleg radiotherapy
Salvage chemotherapy regime at 1st
relapse
BEP x 3
Modified BEP x 4
BEP x 4
Other
Salvage treatment at relapse
22 patients relapsed
First relapse
1
Second relapse
4 salvage
radiotherapy
2
18 alive and
disease free
1
1 radiotherapy
3 cisplatin containing
chemotherapy
(TIP, EP)
Third relapse
1 x4 TIP chemotherapy
2 alive and
disease free
1 dead
1 alive and
disease free
Conclusions
21 (95%)
1 (5%)
•
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
18 (82%)
4 (18%)
8 (44%)
6 (33%)
1 (6%)
3 (17%)
18 salvage
chemotherapy
Corresponding author: Dr. Caroline Chau
[email protected]