Germ Cell Tumors Flashcards
What are the risk factors for Germ Cell Tumors?
1) Prior Hx of GCT
2) FHx of GCT
3) Cryptorchidism
4) Testicular dysgenisis
5) Klinefelter syndrome (47XXY)
Which is more sensitive to RT? Seminioma or NSGCT?
Seminoma
What is the ratio of the composition of residual mass in GCT?
40% Fibrous tissue
40% Teratoma
20% Disease
Why do we need to resect a Teratoma?
1) Resistant to chemo and RT regimens for testicular GCTs
2) Recurrence can occur if viable GCT present in the residual mass
3) Malignant transformation can occur
- sarcomas/ adenoCas can arise from Teratoma. These can be resistant to chemo used for testicular GCTs and are a/w poor prognosis
4) Organ function may be compromised
Tell me about the S staging in the staging of GCT
Sx:N.A. /not performed
S0: Normal
S1:
LDH 10 X NI or
hCG >50 000 mIu/mL or
AFP >10 000 ng/L
What is the M staging for GCT?
M0 no distant mets
M1 distant mets
- M1a: non regional nodal or pulmonary mets
- M1b: distant mets
Tell me about the pathologic nodal staging
pN1 =
- Mets with a LN mass 2cm or less in greatest dimension, and
- less than or equal to 5 LN+, none >2cm
pN2 =
- LN mass >2cm, but not more than 5 cm; OR
- > 5LN positive, but none >5cm; OR
- evidence of Extranodal extension of tumor
pN3 =
- Mets with a LN mass >5cm
Tell me about the T staging for GCT
pT0 =
No evidence of primary tumor (eg histological scar)
pTis =
Intratubula Germ cell neoplasia (Carcinoma-in-situ)
pT1 =
- Tumor limited to testis and epididymis without vascular/lymphatic invasion;
- Tumor may invade into the tunica albuginea but NOT the tunica vaginalis
pT2 =
- Tumor limited to the testis and epididymis with vascular/lymphatic invasion, OR
- Tumor extending through the tunica albuginea with involvement of the tunica vaginalis
pT3 =
- Tumor invades the spermatic cord with or without vascular/lymphatic invasion
pT4 =
- Tumor invades the scrotum with or without vascular/lymphatic invasion
M1a + S0 = what stage?
Stage IIIA
M1a + S1 = what stage?
Stage IIIA
M1b = what stage?
Stage IIIC
Nodal involvement = what stage?
Stage II
N1 = Stage IIA at least
N2 = Stage IIB at least
N3 = Stage IIC at least
What is stage IS?
pTx N0 M0 S1-3
What is the approximate half life of AFP and hCG ?
AFP = 5-7 days hCG = 1.5 to 3 days
What is the risk of Contralateral CIS?
5-10%
When do we consider Contralateral testicular biopsy?
Controversial
Only if nudes ended testes/atrophy
Name me the types of GCT.
1) Seminoma
- Seminoma with syncytiotrophoblastic cells
2) Nonseminomatous GCT
- Teratoma (Dermoid cyst, mono dermal Teratoma, Teratoma with somatic type malignancy)
- Trophoblastic tumors (Choriocarcinoma)
- Yolk Sac tumor (endodermal sinus tumor)
- Mixed GCT
- Embryonic carcinoma
3) Spermatocytic Seminoma
- Spermatocytic Seminoma with sarcoma
Name me the sex cord-stromal tumors
1) Sertoli Cell
2) Leydig Cell
3) Granulosa cell
4) Mixed types
5) Unclassified
What are the main morbidities with RPLND?
1) Retrograde ejaculation resulting in infertility
2) Bowel dysfunction
3) Lymphoedema
4) Chylous ascites
What are the possible toxicities from adjuvant chemotherapy for GCT?
1) 5dB hearing loss
2) 5% reduction in lung function
3) 10% decline in GFR
4) 20% long-term peripheral neuropathy
5) 30% impaired spermatogenesis at 3 years
6) Increased risk of CVS toxicities
7) risk of 2nd malignancies
- 2x increase in solid tumors 10 years after treated GCT
- 0.5% risk of developing leukemia, related to total dose of Etoposide
RPLND vs 1# BEP in Stage I disease. Which is better and why?
AUO trial JCO 2008 by Albers et al.
N=400
Randomized into 2 arms after orchidectomy:
60% of patients are pT1 tumors
- RPLND performed according to community standards
- 1# BEP
F/u 5 years, RESULTS:
- 2y RFS: 99.5% (Chemo) vs 92%
Tell me about the SWENOTECA management program for Clinical Stage I NSGCT
Torgrim Tandstad JCO 2009
Aim: reduce risk of relapse and thereby reducing need for salvage chemo, but maintain a high cure rate.
N=750 Treatment strategy depended on presence or absence of vascular tumor invasion. 2 big groups: 1) Vascular invasion present - BEP 1 or 2 # (patient's Choice) 2) Vascular invasion not present. This is then divided into 2 further groups according to pt's choice : (A) Surveillance (B) BEP 1 cycle
RESULTS:
F/u 5 years:
Recurrence rate: 42%(VASC+) s 13% (VASC -)
After 1 course of BEP, 3% of VASC+ and 1% of VASC- patients relapsed
CONCLUSION:
- 1# BEP reduced the risk of relapse by ~90% in both VASC+ and VASC- CS1 NSGCT
What are the treatment options for CS IA/IB pure Seminoma?
1) Surveillance
- for pT1 or pT2 tumors
2) Single agent Carboplatin AUC 7 X 1 cycle or 2 cycles
3) RT
Tell me about the MRC TE19/EORTC 30982 Study.
Oliver et al. First in Lancet 2005, updated JCO 2011
Aim: Compare RT with chemotherapy in Seminoma treatment
N=1500
2 arms:
1) RT (para-aortic strip or dog-leg field)
2) 1# Caroboplatin AUC 7
RESULTS:
2y RFS 97% vs 98% (Chemo)
3y RFS 96% vs 95% (Chemo)
5y RFS 96% vs 95% (Chemo)
Patients given Carboplatin less lethargic and less likely to take time off work than those given RT
2nd primary testicular GCT reported in 2% (RT) vs 0.5% (Chemo)
- at 6.5y, clear reduction I the rate of Contralateral GCT. HR 0.2
Between Carboplatin and CDDP, which would you choose and why?
CDDP
Bajorin et al JCO 1993
N=270 with good-risk GCTs, were randomized to:
1) 4# EP Q21days
- Etoposide 100mg/m2 D1-5
- CDDP (20) D1-5
2) 4# EC Q28days
- Etoposide 100mg/m2 D1-5
- Carboplatin (500) D1
RESULTS:
CR: 90% (EP) v 88% (EC)
Median f/u of 2 years, EFS and RFS inferior for pts treated with EC
No difference in OS evidence
Tell me about the 2nd Spanish GC cancer Cooperative study
Jorge Aparicio JCO 2005
Aim: To assess the efficacy of a risk-adapted treatment policy for stage I Seminoma.
N=300
CS I Seminoma after orchidectomy
2 arms:
1) Surveillance
- No risk factors
- 30% of patients
2) 2# Adjuvant Carboplatin
- >4cm tumors (40% of patients)
- Rete testis involvement (10.5%)
- both risk factors (16%)
RESULTS:
- chemo well-tolerated. 8% p/w G3/4 toxicity
- Relapses in 3% (chemo) an 6% (surveillance)
- 5y DFS 93% (Surveillance) and 96% (Chemo)
- Overall 5y survival 100%
Conclusion: Adjuvant Carboplatin is effective in reducing the relapse rate in those with Stage I Seminoma with risk factors
- risk-adapted strategy is safe and feasible.
