Terapia sistémica en cáncer de testículo

Systemic therapy in testicular cancer
Mauricio Lema Medina MD
Clínica de Oncología Astorga, Clínica SOMA, Medellín
Simposio ACHO GU, Septiembre 23-24 de 2016, Bogotá

Mauricio Lema <mauriciolema@yahoo.com>Togarciaj4@ccf.org
Today at 7:36 AM
Hola Jorge, espero que estés bien. Te escribo para pedirte permiso para usar tu conferencia de cáncer de
testículo de 2012 que diste en Medellín, que creo es la mejor conferencia que he escuchado sobre GCTs.
Tengo que hablar del tema, y voy a tomarla como base.
Te agradezco que me autorices su uso (con crédito, por supuesto).
Un abrazo,
Mauricio Lema Medina MD
Garcia, M.D. Jorge A <GARCIAJ4@ccf.org>ToMauricio Lema
Today at 8:30 AM
Claro Mauricio
Si necesitas algunas otras slides me avisas
Un abrazo
Jorge

Bosl G, Warde P, Heidenreich A, ASCO 2016: Testicular Cancer – a Multidisciplinary Case Based Discussion

Not all Testis Cancers are the same
 Seminoma
- No AFP
- Spurious elevations of HCG
- Path must have 100% + seminoma cells
- Radiotherapy or chemotherapy (recently)
Courtesy of Jorge A. García

Not all Testis Cancers are the same
 Non-Seminoma
- Any serum marker
- Path could be mixed
- Observation of RPLND

 Non-Seminoma
- % Embryonal component
- Lymphovascular invasion
- Paratesticular involvement
 Seminoma
- Tumor size (> 4cm)
- Retetestis invasion
Pathological Features & Relapse

 Stage I
 Stage IIa
- Microscopic
- LNs < 2cm
 Stage IIb
- LNs 2-5cm
 Stage IIc (LNs > 5cm) = Advanced disease
Early Testis Cancer Staging

 Observation/surveillance
- 15% risk of occult disease
 Radiotherapy
 Chemotherapy with Carboplatin (only scenario where
this agent is accepted in testis cancer)
Treatment Options for Stage I Seminoma

The Argument for Carboplatin for Stage I Seminoma
 Carboplatin is the most effective way to prevent relapse
 Carboplatin is associated with minimal acute toxicity
 Radiation therapy is associated with unacceptable late
toxicity
 The risk of late complications from single agent carboplatin
is hypothetical whereas the risk of late complications from
radiation therapy is well documented
 Carboplatin appears to reduce the risk of second primary
germ cell tumors

Stage I Seminomas: Outcomes in published reports
Management
Number of
Patients Relapse
Median Time To
Relapse
(range) 5-year DSS
Surveillance 1032 18.4% 99.6%
Carboplatin
(2 cycles)
660 2.0%
9 – 15 mo
(4 – 28)
100%
Radiation 4630 3.8%
13 – 26 mo
(1 – 102)
99.7%

EORTC/MRC Randomized Controlled Trial:
Single Dose of Carboplatin vs. Radiation
Arm 3-yr Relapse Rate
RT 4.1% (2.9 – 5.6)
Carbo (1 cycle) 5.2% (3.6 – 7.5)
Arm N Relapses 2 year
RFS
3 year
RFS
Seminoma
Deaths
RT 904 36 96.7%
(95.3 – 97.7)
95.9%
(94.4 – 97.1)
1
Carbo
(1 cycle)
573 29 97.7%
(96.0-98.6)
94.8%
(92.5 – 96.4)
0
RT Oliver, Lancet, 2005;366:293Courtesy of Jorge A. García

EORTC/MRC Trial: 1 cycle Carboplatin v. Radiation:
Relapse-Free Survival
RT Oliver, Lancet, 2005;366:293

Carboplatin: one or two cycles?

Toxicity from
Single Agent
Carboplatin
AUC = 7 x 2 cycles
400 mg/m2
x 2 cycles

Disability and toxicity during treatment:
Radiation vs. Carboplatin RCT
 Radiation
- More missed work
- More moderate to severe
lethargy
- More dyspepsia
 Carboplatin
- More thrombocytopenia

Radiotherapy Carboplatin
Other
TOTAL
Germ-Cell
Tumors
10 2
4 3
14 5
New Primary Cancers: EORTC/MRC RCT
RT Oliver, Lancet, 2005;366:293

Sperm count in Swedish clinical stage I testicular cancer
patients following modern adjuvant treatment.
Weibring K, Proc ASCO 2016, 4542
182 pts Stage I GCT
Surveillance: 28 pts
Single-dose carboplatin: 22 pts
BEP x1: 62 pts
RT: 70 ptsSperm Count over time

What’s wrong with radiation?
 Burden of treatment
 Secondary Cancers
 Cardiovascular Dz
 Deaths from digestive
diseases

Do the math
 100 men with stage I seminoma
- 80-82 cured with orchiectomy
- 18-20 destined to relapse on surveillance
- 3-5 relapse after radiation
- 13-17 relapses prevented by radiation
- 6-13 cancers result from radiation

False Arguments Against Carboplatin
 Claim: Relapses after radiation are above the diaphragm
so surveillance CT scans are not needed
 Fact: In the RT vs. Carbo trial, 41% of relapses in the RT
arm were below the diaphragm
In the two large RCTs of radiation for seminoma, two
thirds of relapses presented with disease below the
diaphragm

 Claim: Relapses after radiation are above the diaphragm
so surveillance CT scans are not needed
 Fact: In the RT vs. Carbo trial, 41% of relapses in the RT
arm were below the diaphragm
In the two large RCTs of radiation for seminoma, two thirds
of relapses presented with disease below the diaphragm
 Claim: Late relapses are a risk after carboplatin
 Fact: Relapses more than five years after treatment have
been reported following RT but NOT following
carboplatin.
The latest relapse after 2 cycles carbo was at
28 months

 Claim: Carboplatin isn’t good enough for GCTs – cisplatin is
needed
 Fact: Disease specific survival is between 99.9% and 100%.
Two cycles of carboplatin results in a relapse rate of 2%

 Claim: Carboplatin isn’t good enough for GCTs – cisplatin is
needed
 Claim: Carboplatin causes secondary malignancies.
 Fact: Carboplatin has been associated with secondary
leukemias in women treated for ovarian cancer but not at
the doses used for seminoma.

 Claim: Carboplatin isn’t good enough for GCTs – cisplatin is needed
 Claim: Carboplatin causes secondary malignancies.
 Fact: Carboplatin has been associated with secondary
leukemiasin women treated for ovarian cancer but not at
the doses used for seminoma.
 Claim: Modern radiation is safe
 Fact: We have no long-term follow-up data on modern radiation

Summary: Radiation Therapy
 Radiation therapy has been proven to result in substantial
late morbidity and mortality
 The long-term safety of current radiation therapy which
uses lower doses and smaller fields remains unproven
 The switch to lower doses and small radiation fields has
resulted in more infra-diaphragmatic relapses after
radiation

Summary: Carboplatin
 Single-Agent Carboplatin is very well tolerated
 Two cycles of single-agent carboplatin has resulted in the
lowest published relapse rates for stage I seminoma
 One cycle of carboplatin results in equivalent relapse rates
to radiation therapy
 With over 1200 patients treated with carboplatin in
published reports, only one unsalvageable relapse has
been reported
 Whether or not single-agent carboplatin causes any
significant late morbidity or mortality remains unknown

Stage II Seminoma
RT CT
BEP x3
EP x4
NCCN Guidelines Version 2.2016

Metastatic Low-Risk Seminoma
Carboplatin AUC 10
PET-CT day 17-22
CMR No CMR
Carboplatin AUC 10 x3* (total) Carboplatin AUC 10 x4* (total)
*Cycles when plt>75, and rising
CarPET: Carboplatin AUC 10 in metastatic seminoma – early PET scanning
can reduce the amount of treatment whilst maintaining outcome – A Phase
II Trial
Shamash J, Proc ASCO 2016, Abstract 4545

Metastatic Low-Risk Seminoma
Carboplatin AUC 10
PET-CT day 17-22
CMR No CMR
Carboplatin AUC 10 x3* (total) Carboplatin AUC 10 x4* (total)
*Cycles when plt>75, and rising
CarPET: Carboplatin AUC 10 in metastatic seminoma – early PET scanning
can reduce the amount of treatment whilst maintaining outcome – A Phase
II Trial
n=48
n=21 n=26
Median follow-up of 25.8 mo:
OS 100%
PFS: 97.1%
Shamash J, Proc ASCO 2016, Abstract 4545

 Observation/surveillance
- 30% risk of occult RPL metastases
 RPLND
 Cisplatin-based chemotherapy
- BEP x1-2
Treatment Options for Stage I NSGCT

Clinical trials of adjuvant chemotherapy in
‘high-risk’ clinical stage I NSGCT (1)
Author / year # of pts. Treatment Relapse (median f/u)
 Oliver, 1992 22 BEP x 2 5% (1 pt) at 43
months; 1 relapse at
6m w/ chemo
response, then
relapse/death
 Abratt, 1994 20 BEP x 2 0% at 31 months
 Cullen, 1996 114 BEP x 2 1.7% (2 pts) at 4
years; 1 PD/death; 1
w/o GCT on retrosp.
review

Clinical Trials of adjuvant chemotherapy in
‘high-risk’ clinical stage I NSGC T (2)
Author / year # of pts. Treatment Relapse (median f/u)
 Pont ‘96 29 BEP x 2 6.9% (2 pts) at 79
months - 1 mature teratoma
s/p sg-> NED; 1 embryonal
w/chemo response, then
relapse/death
 Chevreau ‘97 38 BEP x 2 (33 pts.) 0% at 36 months
PVB x 2 (5 pts.)
 Studer, 2000 59 BEP x 2 (39pts.) 3.3% (2 pts) at 93
PVB x 2 (20 pts.) months; 1 mature teratoma
resected at 22m; 1 stage II
seminoma at 7.5yrs.

Acute and Long-term AEs in Adjuvant Chemo Trials
 Hematologic: G3 leukopenia (3.5%, 18%, 24%); no other
significant toxicity
 GI: G3 emesis (27%, 13%); G2 Alopecia and G1Tinitus
--------------------------------------------------------------------------------------
 Fertility: no change in pre- vs. post-sperm density/motility in two
studies; 2 others with 1-2 pts. with azoospermia (not different
than controls in one study)
 Lung function: no change in PFTs in 2 studies
 Audiometry: high-tone hearing loss (12%, 5%)
 No 11q23 (etoposide-induced) AML reported

Case 2: 23 year-old patient undergoing
BEP cycle #2 for early-stage GCT
Page  47

Advanced Germ Cell Tumors
Defined as Stage IIC or higher
- Any pT/Tx N3 (>5cm) M0
Overall CR’s 70-80%
Poor outcome 20-30%
Identification by risk groups
- International Germ Cell Cancer
Collaborative Group (IGCCCG)

International Germ Cell Cancer
Collaborative Group (IGCCCG)
I – triple C – entre Gs
Page  54

Risk Assessment of Advanced Disease (IGCCCG)
NSGCT - Good Prognosis
 Testis or RP primary, AND
 No nonpulmonary visceral metastases, AND
 Good Markers including all the following:
- AFP < 1,000 ng/ml
- HCG < 5,000 IU/L (1,000 ng/ml)
- LDH < 1.5 x upper limit of normal
 56% of nonseminomas
 5-year PFS 89%
 5-year OS 92%

NSGCT - Intermediate Prognosis
 Testis or RP primary, AND
 No nonpulmonary visceral metastases, And
 Intermediate Markers including any the following:
- AFP >= 1,000 ng/ml and <= 10,000 ng/ml
- HCG >= 5,000 IU/L and <= 50,000 IU/L
- LDH >= 1.5 x Nl and <= 10 x Nl
 5-year PFS 75%
 5-year OS 80%

NSGCT - Poor Prognosis
 Mediastinal primary, OR
 Nonpulmonary visceral metastases, OR
 Poor Markers including any the following:
- AFP >= 10,000 ng/ml
- HCG >= 50,000 IU/L (10,000 ng/ml)
- LDH >= 10 x upper limit of normal
 5-year PFS 41%
 5-year OS 48%

Seminoma
Good Prognosis
 Any primary site, AND
 No nonpulmonary visceral metastases, AND
 Normal Markers
- 90% of seminomas, 5-year PFS 82%, 5-year OS 86%
Intermediate Prognosis
 Any primary site, AND
 Nonpulmonary visceral metastases, AND
 Normal Markers
- 10% of seminomas, 5-year PFS 67%, 5-year OS 72%

Outcomes by IGCCCG risk categories in
GCTs
Page  59
Clinical scenario 5-yr PFS 5-yr OS
Seminoma Good-Prognosis 82% 86%
Seminoma Intermediate-Prognosis 67% 72%
Non-Seminoma Good-Prognosis 89% 92%
Non-Seminoma Intermediate-Prognosis 75% 80%
Non-Seminoma Poor-Prognosis 41% 48%

Treatment for Good-Risk Advanced
Germ Cell Tumors
 Cisplatin, Etoposide and Bleomycin (PEB) x 4
- Standard of Therapy since the late 80’s
 PVB x 4 v PEB x 4 (E = Etoposide or VP-16)
- Randomized Phase III study of 244 patients
- CR 74% v 83% with or without surgery (P not significant)
- High-Tumor Volume (n=157) - CR 61% v 77% (P < 0.05)
- 5-year OS greater with PEB (P < 0.048)
- Less toxicities with PEB
- Paresthesias (p= 0.02)
- Abdominal Cramps (p= 0.0008)
- Myalgias (p= 0.00002)
 Williams SD, et al. NEJM 316, 1987

Clinical Trials for Good-Risk Advanced
Germ Cell Tumors
Goal is to decrease toxicity
Are 4 cycles of PEB better than 3 ??
Administration over 5 days vs. 3 days ??
Bleomycin or not ??
Carboplatin vs. Cisplatin ??

Are 4 cycles of PEB better than 3 ??
Adapted from Einhorn LH, et al. JCO 7:387-391.1989.
de Wit R, et al. JCO 19:1629-1640. 2001.
Institution n Regimen Response Relapses Toxicities
PEB x 4 6% Relapse
SECSG 184 v 98%
PEB x 3 92% NED
74.9% v 73% (p= 0.41) 2-year PFS
PEB x 4 2-year OS (90.4% v 89.4%)
EORTC 812 v (97% v 97.1%) HR 0.93
PEB x 3 HR 1.02 (80%CI 0.71-1.24)
(80%CI 0.61-1.73)

Administration Schedule:
Is it 5 days better than 3 days ?
R
A
N
D
O
M
I
Z
A
T
I
O
N
PEB x 3 for 3 days
(CDDP 50mg/m2 D1-2, VP-16 165mg/m2 D1-3
Bleomycin 30mg D1, D8, D15 for 3 cycles)
PEB x 3 for 5 days
(CDDP 20mg/m2 D1-5, VP-16 100mg/m2 D1-5
PEB x 3 + PE x 1 for 3 days
(CDDP 50mg/m2 D1-2, VP-16 165mg/m2 D1-3
PEB x 3 + PE x 1 for 5 days
(CDDP 50mg/m2 D1-2, VP-16 165mg/m2 D1-3
n = 812
de Wit R, et al. JCO 19:1629-1640. 2001

Administration Schedule: Is it 5 days better than 3 days ?
3days (n = 333) 5 days (n = 329)
_____________________ _______________________
Variable No. % No. % p
Complete Response 247 74.1% 240 72.9% 0.718
(Chemo + Surgery)
2 year PFS 89.7% 88.8%
HR 1.05 (80% CI 0.78-1.41)
96.4% 97.5%
2 year OS
HR 0.80 (80% CI 0.4-1.42)
Adapted from de Wit R, et al. JCO 19:1629-1640. 2001

What is the Role of Bleomycin ?
 ECOG (Loehrer PJ, et al. JCO 13:470-476, 1995)
- Randomized 178 pts to PEB x 3 v PE x 3 (American regimen)
- Complete Response 94% v 88% (p= not significant)
- Greater Treatment Failures in PE arm (post-chemo masses and relapses
from CR) (p= 0.004)
- Overall Survival 95% v 86% (p= 0.01)
 EORTC (de Wit R, et al. JCO 15:1837-1843,1997)
- Randomized 395 pts to PEB x 4 v PE x 4 (European regimen)
- Complete Response 95% v 87% (p= 0.0075)
- TTP (p= 0.136) and Overall Survival (p= 0.262)
- Neurotoxicity and Pulmonary Toxicity greater with PEB
(p< 0.001)

Carboplatin instead of CDDP ?
 MSKCC (Bajorin DF, et al. JCO 11:598-606, 1993)
- Multicenter Phase III - Randomized 270 pts to EP x 4 v EC x 4
- Complete Response 90% v 88% (p= 0.32)
- Event-Free Survival inferior for EC arm (p= 0.02)
- Relapse-Free Survival inferior for EC arm (p= 0.005)
- No difference in Overall Survival (p= 0.52)
 MRC/EORTC (Horwich A, et al. JCO 15:1844-1852, 1997)
- Multicenter Phase III - Randomized 598 pts to PEB x 4 v CEB x 4
- Complete Response 94.4% v 87.3% (p= 0.009)
- 1-year failure-free rates 91% (95% CI, 88%-94%) and 77%
(95% CI, 72%-82%) p < 0.001
- Overall Survival 97% v 90% (p= 0.003)

IGCCCG Good-Risk GCT
EPx4 BEPx3
NCCN Guidelines Version 2.2016

Clinical Trials for Intermediate and Poor-Risk
Advanced Germ Cell Tumors
Goal is to Increase Efficacy
 Exploiting agents used in the salvage setting
 Evaluation of the role of dose escalation
 Alternating non-cross resistant Chemotherapy
 Evaluation of HDC-PSCT as in the salvage setting

Poor Risk – Advanced NSGCT’s
 Suboptimal outcome of poor-risk patients
- 5-year PFS 41% and 5-year OS 48%
 Goal is to increase efficacy
- Alternating non-cross-resistant chemotherapy
- Dose escalation
- Exploiting agents used in the salvage setting including
HDCT-ASCT
 Single Institutional Trials (MSKCC)*
- VAB-6 and VAB-6 + EP (CR’s = 45% and 46%)
- VAB-6 + HDCT(EC)-ASCT (CR = 56%)
- VIP X4 vs.VIPX2 > HDCT (EC)-ASCT (CR = 53%)
*Motzer et al. J Clin Oncol 1997;15:2546-2552.

Eligibility/Stratification
• Modified IGCCCG*
- Poor vs. Intermediate
• Center (CALGB-MSKCC-
SWOG and ECOG)
Randomization(N=218)
Cisplatin 20 mg/m2 daily x 5 days
Etoposide 100 mg/m2 daily x 5 days
Bleomycin 30 mg days 1, 8, and 15
G-CSF days 5 mcg/kg days 7-16 excluding
bleomycin days
Carboplatin 600 mg/m2 daily x 3 days
Etoposide 600 mg/m2 daily x 3 days
Cyclophosphamide 50 mg/kg x 3 days
Autologous stem cells day 5
Growth factor support
BEP X2 – HDCT (CEC) X2
BEP X4
Target accrual was 218 pts to detect an improvement of 20% in CR at 1 year
with an alpha=0.05 and 80% power
*Motzer et al. J Clin Oncol 1997;15:2546-2552.
Adapted from Bajorin DF, et al. Abstract 4510, ASCO 2006.
Intergroup Study of Poor-risk GCT

Outcome: Response Rate
BEP (%)
(n=111)
BEP + HD (%)
(n=108)
Complete response (CR) 55 56
CR to chemotherapy 46 48
CR to chemotherapy + Surgery 9 8
Incomplete response 44 43
PR – negative markers 5 10
1-year durable CR rate 48 52
Completion of C1-2 BEP 99 100
Completion of C3-4 BEP or HD-CEC 88 77

Event-Free Survival and Overall Survival
BEP alone (110 Pts, 60 Failures)
BEP + HDT (107 Pts, 55 Failures)
PROPORTIONEVENT-FREE
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
MONTHS
0 12 24 36 48 60 72 84 96 108 120
p=0.40
BEP alone (111 Pts, 77 Alive)
BEP + HDT (108 Pts, 73 Alive)PROPORTIONSURVIVING
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
MONTHS
0 12 24 36 48 60 72 84 96 108 120
p=0.94
Overall SurvivalEvent-Free Survival

Long-Term Outcomes According to
Initial Marker Decline Status
Sat Decline (96 Pts, 78 Alive)
Unsat Decline (69 Pts, 46 Alive)PROPORTIONSURVIVING
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
MONTHS
0 12 24 36 48 60 72 84 96 108 120
Sat Decline (95 Pts, 38 Failures)
Unsat Decline (67 Pts, 37 Failures)
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
MONTHS
0 12 24 36 48 60 72 84 96 108 120
Overall SurvivalEvent-Free Survival
p=.02
p=0.03
1-yr Durable CR 63% vs 45% 2-yr survival 83% vs 68%

Marker Decline Status and
Event-free Survival
Satisfactory Marker
Decline
Unsatisfactory Marker
Decline
P=.50 P=.03
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
MONTHS
0 12 24 36 48 60 72 84 96 108 120
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
MONTHS
0 12 24 36 48 60 72 84 96 108 120
1-yr durable CR 58% vs 66% 1-yr durable CR 61% vs 34%

Marker Decline Status and
Overall Survival
Satisfactory Marker
Decline
Unsatisfactory Marker Decline
2-yr survival 78% vs 85% 2-yr survival 78% vs 55%
BEP + HDT (38 Pts, 28 Alive)
PROPORTIONSURVIVING
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
MONTHS
0 12 24 36 48 60 72 84 96 108 120
BEP + HDT (33 Pts, 25 Alive)
PROPORTIONSURVIVING
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
MONTHS
0 12 24 36 48 60 72 84 96 108 120
P=.34 P=.10

Mature results of the GETUG 13 phase III trial in
poor-prognosis germ-cell tumors
Fizazi K, Proc ASCO 2016, Abstract 4504

Paclitaxel, Ifosfamide, and Cisplatin Efficacy for
First-Line Treatment of Patients With
Intermediate- or Poor-Risk Germ-Cell Tumors
Feldman DR, JCO, 2016
High-Risk (or Modified Intermediate-
Risk GCT_ LDH greater 3x ULN)
Paclitaxel 120 mg/m2, d1, d2
Ifosfamide/MESNA 1200 mg/m2, d1-d5
Cisplatin 20 mg/m2, d1-d5

MESNA 120 mg/m2 30 minutes Ifosfamide, d1-d5
Dexamethasone 20 mg in the night before and morning of Paclitaxel
Anti H1/H2 before Paclitaxel
5-HT3 antagonist daily
Aprepitant on d4-d6
Dexamethasone 12 mg/d on d3-d7
Pegfilgrastim 6 mg on d6 or d7
Levofloxacin 500 mg/d on d7-d13

MESNA 120 mg/m2 30 minutes Ifosfamide, d1-d5
Dexamethasone 20 mg in the night before and morning of Paclitaxel
Anti H1/H2 before Paclitaxel
5-HT3 antagonist daily
Aprepitant on d4-d6
Dexamethasone 12 mg/d on d3-d7
Pegfilgrastim 6 mg on d6 or d7
Levofloxacin 500 mg/d on d7-d13
If ANC less than 1000 or Plat less than 90,000/uL on d1, CT was delayed 1 week

Paclitaxel,
Ifosfamide, and
Cisplatin Efficacy for
First-Line Treatment
of Patients With
Intermediate- or
Poor-Risk Germ-Cell
Tumors

High-dose Chemotherapy and Autologous Peripheral-
Blood Stem Cell Transplant for Relapsed Metastatic
Germ-Cell Tumors: The Indiana University Experience.
Adra N, Proc ASCO 2016, Abstract 4505

Case 4
Page  135
Bosl G, Warde P, Heidenreich A, ASCO 2016: Testicular Cancer – a Multidisciplinary Case Based Discussion

Risk Assessment of Residual Masses after
Chemotherapy for Seminoma
 Observed in 60-85%
 20-25% with (+) masses have residual malignancy
 42% of residual mass > 3cm will have viable malignant cells and
should undergo surgery
 Masses < 3cm can be observed
 PET has been shown to be a predictor for malignancy:
(De Santis M, et al. JCO 19, 2001)
 Predicting: 96% of masses < 3cm / 100% of masses > 3cm

Risk Assessment of Residual Masses after
Chemotherapy for NSGCT
 Observed in 30-40%
 15% with (+) masses have viable malignant cells
 Histology is a predicting factor for survival:
- Carcinoma 15% with CR 60-70%
- Teratoma 35% with CR 85%
- Necrosis/Fibrosis 50% with CR 85-90%
 Role of Surgery
 Role of Chemotherapy post-surgery

Viable Cells After Chemotherapy for NSGCT
International Study Group
Multivariate Analysis of Survival
PFS OS
Unfavorable Prognostic Factors Risk Ratio 95 % CI P Risk Ratio 95% CI P
Incomplete surgery 2.75 1.51 – 4.98 <.001 3.82 1.94 – 7.52 <.001
Viable malignant cells > = 10 2.25 1.28 – 3.94 .005 3.31 1.62 – 6.78 .001
Poor or intermediate IGCCC 2.58 1.34 – 4.97 .005 3.22 1.32 – 7.82 .01
Prognostic Index
5 – Year PFS 5 – Year OS
Risk Group
No of Adverse
Factors
Patients
(%) % 95% CI % 95% CI
Favorable 0 22 90 79 - 100 100
Intermediate 1 40 76 65 – 87 83 73 - 93
Poor >= 2 38 41 28 - 54 51 37 - 65
Adapted from Fizazi K, et al. JCO 19, 2001
- 238 pts with viable malignant cells in their resected specimen
- 5 year PFS and OS = 64% and 73%

Summary of Management for Advanced Germ Cell
Tumors
 Stratification by IGCCCG
 Good-risk
- PEB x 3 (if Pulmonary toxicity) >PE x 4
 Intermediate-risk
- PEB x 4 v Clinical Trial
- VIP-TIP
 Poor-risk
- PEB x 4 v Clinical trial
- VIP-TIP

Summary of Management for Advanced
Germ Cell Tumors
 Salvage Therapy
- VIP - TIP - HDCT/PSCT
 Post-chemotherapy residual masses
- Observation if <3cm (seminoma)
- Resection if >3cm (seminoma)
- Resection in NSGCT vs. Salvage chemotherapy (poor-risk)

Terapia sistémica en cáncer de testículo

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