The document discusses castrate-resistant prostate cancer (mCPRC). Some key points: - mCPRC is the leading cause of death in men with prostate cancer and most deaths are due to mCPRC. Median survival is around 2 years. - New treatments have improved survival for mCPRC. About 90% of prostate cancers initially respond to androgen deprivation therapy (ADT) but mCPRC often rapidly develops, especially if PSA nadir is >4 ng/mL. - mCPRC occurs when tumor progression continues despite castrate levels of testosterone (<50 ng/dL). Most mCPRC is still dependent on the androgen receptor

1. Cancer de
Prostata
Resistente a la Castracion
(CPRC)
DR. LUIS MIGUEL ZETINA TOACHE
ONCOMEDICA

2. GENERALIDADES: CPRC
 1ERO INCIDENCIA EN HOMBRES Y 2DA CAUSA DE MUERTE
 ~ 240,000 nuevos casos y 29,000 muertes relacionadas a
cancer de prostata en USA en 2012[1].
 La mayoria de muertes son por mCPRC. SV: 2 años.
 NUEVOS TRATAMIENTOS HAN IMPACTADO LA SV.
 La SV de celula cancerosa depende de la activacion del RA [2].
 AR se expresa PERMANENTEMENTE.
 ~ 90% de Ca. de prostata responden a ADT, pero
tipicamente CPRC se desarrolla rapidamente ,
especialmente si el nadir del PSA es > 4 ng/mL[3,4]
 CRPC resulta de la sobre regulacion del RA y la re-expression
de los genes androgen-dependientes[4,5]
1. American Cancer Society. Available at: http://www.cancer.org. 2. Sharifi N,
et al. Clin Cancer Res. 2008;14:4691-4693. 3. Gelmann EP. J Clin Oncol.
2002;20:3001-3015. 4. Hussain M, et al. J Clin Oncol. 2006;24:3984-3990. 4.
Holzbeierlein J, et al. Am J Pathol. 2004;164:217-227.

3. RECEPTOR
ANDROGENICO

4. clinicaloptions.com/oncology
Expert Guidance in Defining and Treating CRPC
S9346: PSA ≤ 4 ng/mL After 7 Months
of AD Is a Strong Predictor of Survival
Hussain M, et al. J Clin Oncol. 2006;24:3984-3990. Reprinted with permission. © 2009 American
Society of Clinical Oncology. All rights reserved.
Mos After End of Induction
Patients(%)
100
80
60
40
20
0
1200 24 48 72 96
No. at risk:
PSA ≤ 0.2 ng/mL 453 210 63
0.2 < PSA ≤ 4.0 219 77 20
PSA > 4.0 92 17 7
Median
At Risk Deaths in Mos
PSA ≤ 0.2 602 199 75
0.2 < PSA ≤ 4.0 360 166 44
PSA > 4.0 383 322 13
P < .0001

5. • CP Resistente a la castracion: Progresion tumoral
a pesar de nivel de Androgenos de <50ng/dl
• *CP Hormono-refractorio: Tumores que ya no
responden a manipulacion hormonal
• *CP Androgeno-independente : Tumors no
dependen del señales de los receptores androgenicos
(RA) para crecimiento y sobrevida

6. clinicaloptions.com/oncology
Expert Guidance in Defining and Treating CRPC
What Determines Whether a Patient
Is Castrate Resistant?
If the answer to both is yes,
the patient is castrate resistant
 Has an attempt been made to suppress the patient’s
testosterone production through orchiectomy or hormone
suppression therapy with an LHRH agonist with or without
an antiandrogen (ie, ADT)?
 Is the patient’s testosterone level < 50 ng/dL?

7. clinicaloptions.com/oncology
Expert Guidance in Defining and Treating CRPC
Definition of CRPC: Progression
 CRPC will develop in nearly all patients receiving ADT
– Definition: rising PSA with nodal or visceral lesions or growth of measurable
disease despite castrate testosterone levels[1]
 Prostate cancers that progress despite castrate levels of testosterone are
classified as CRPC
 According to the 2008 guidelines published by the Prostate Cancer Clinical
Trials Working Group, several criteria are used to define disease
progression[2]
– ≥ 2 bone lesions
– Reappearance of primary prostate tumor in prostatic fossa after surgery
– New lesions at other sites of metastasis
1. Scher HI, et al. J Clin Oncol. 2005;23:8253-8261.
2. Scher HI, et al. J Clin Oncol. 2008;26:1148-1159.

8. clinicaloptions.com/oncology
Expert Guidance in Defining and Treating CRPC
Progressive CRPC
 Defined using clinical symptoms identified in TAX-327 and
SWOG 99-16 trials
Adapted from Scher HI, et al. J Clin Oncol. 2008;26:1148-1159.
Clinical Symptom, %
TAX 327 Trial
(n = 1106)
SWOG 99-16 Trial
(n = 770)
Rising PSA level 87 90
Bone metastasis 93 88
Substantive pain 36 36
Soft tissue lesion
 Lung or liver 22 19
 Lymph nodes 18 24

9. clinicaloptions.com/oncology
Expert Guidance in Defining and Treating CRPC
Criteria Defining CRPC Progression for
Clinical Trial Enrollment
 Identified by the Prostate Cancer Clinical Trials Working Group 2
Adapted from Scher HI, et al. J Clin Oncol. 2008;26:1148-1159.
Variable Description
PSA
 Obtain sequence of rising PSA levels (min 1-wk intervals)
 Min 2.0 ng/mL starting value
 Estimate PSA-DT before therapy, if ≥ 3 values available ≥ 4 wks apart
Target lesions
 Nodal or visceral progression sufficient for trial entry independent of PSA level
 Measurable lesions not required for entry
 Soft-tissue (nodal or visceral) lesions recorded as target or nontarget (RECIST)
 Only lymph nodes ≥ 2 cm should be used to assess change in size
 Record nodal and/or visceral disease separately
Primary site
prostate or
prostate bed
 Record previous treatment of primary tumor
 Assess presence or absence of disease using directed pelvic imaging
– CT, MRI, PET/CT, endorectal MRI, transrectal ultrasound
Bone
 Progression: appearance of ≥ 2 new lesions
 Confirm ambiguous results with other imaging modalities (CT or MRI)
Other disease sites  Treated epidural lesions and no other epidural progression

10. Cancer de Prostata (CR)
Pesimismo.....DOLOR
Compresión
MedularAnemia
Hipercalcemia
Fracturas
Discapacidad

12. By ANDREW POLLACK
Published: June 27, 2011
http://www.nytimes.com/pages/health/index.html

15. N Engl J Med 2004;351:1502-12.
Copyright © 2004 Massachusetts Medical Societ

16. Primary Endpoint: Overall Survival
De Bono et al. Lancet, 2010, 376:1147-54
30% reduction in the risk of death
MP CBZP
Median OS (months) 12.7 15.1
Hazard ratio 0.70
95% CI 0.59–0.83
P value <0.0001
ProportionofOS(%)
100
80
60
40
20
0
Mitoxantrone
Cabazitaxel
0 6 12 18 24 30
28%
17%
Time (months)

17. Original Article
Sipuleucel-T Immunotherapy for Castration-
Resistant Prostate Cancer
Philip W. Kantoff, M.D., Celestia S. Higano, M.D., Neal D. Shore, M.D., E. Roy
Berger, M.D., Eric J. Small, M.D., David F. Penson, M.D., Charles H. Redfern, M.D.,
Anna C. Ferrari, M.D., Robert Dreicer, M.D., Robert B. Sims, M.D., Yi Xu, Ph.D., Mark
W. Frohlich, M.D., Paul F. Schellhammer, M.D., for the IMPACT Study Investigators
N Engl J Med, Volume 363(5):411-422
July 29, 2010

19. Superior Efficacy in Preventing Time to First Skeletal-Related Event (SRE) in
Prostate Cancer Patients with Bone Metastases vs Zoledronic Acid

22. Hormono Terapia 2da línea
MDV 3100, Cabozitinib, Alpharadin, Xgeva

26. GLB.CAB.11.08.09 9/11
Los beneficios de un enfoque multidisciplinario
en el tx.del mHRPC
• El enfoque multidisciplinario puede servir al cuidado del paciente
– Identificación de oportunidades para una terapia apropiada en los primeros estadios de
la enfermedad metástasica.
– Asegurar la derivación oportuna y exitosa
– Alineación de expectativas mutuas y objetivos de tratamiento
26
En pacientes con un alto riesgo
de progreso de la enfermedada
“El comienzo temprano de un
tratamiento de quimioterapia [de
primera línea] en pacientes [con
mHRPC] resulta en una mejora
significativa de la sobrevida a
diferencia de aquellos pacientes en
los que se retrasa el inicio del
tratamiento sistémico citotóxico”.
- Asociación Europea de Urología
Abril 2011
1. Sternberg CN, Krainer M, Oh WK, et al. BJU Int. 2007;99(1):22-27.
2. 2. Gomella LG, Lin J, Hoffman-Censits J, et al. J Oncol Pract. 2010;6(6): e5-e10. 3. Mottet N, Bellmunt J,
Bolla M, et al. Eur Urol. 2011;59(4):572-583.
Enfermera oncológica
Urólogo
Oncólogo
médico
Oncólogo
Radio
Terapeuta
PACIENTE

27. GLB.CAB.11.08.09 9/11
El cuidado multidisciplinario del cáncer de próstata
puede mejorar el resultado de la enfermedad en el paciente
• Los pacientes con cáncer de próstata en Estadio III/IV bajo el cuidado de un programa
multidisciplinario de cuidado del cáncer de próstata experimentaron resultados de sobrevida
mejores, en comparación con los datos registrados por SEER en los Estados Unidos.
27
1. Gomella LG, Lin J, Hoffman-Censits J, et al. J Oncol Pract. 2010;6(6): e5-e10.
2. Valdagni R, Albers P, Bangma C, et al. Eur J Cancer. 2011;47(1):1-7.
Tiempo (meses) Tiempo (meses)
ESTADIO III (T3 NO MO)
ESTADIO IV (T4 NO MO)
Registro = Registro
NCI SEER = TJ U
Registro = Registro
NCI SEER = TJ U
Probabilidaddesobrevida
Probabilidaddesobrevida
NCI SEER (n=1489)
Prueba estadística df P
Prueba de log-rango 11,4921 1 0,0007
Wilcoxon 10,4687 1 0,0012
NCI SEER (n=298)
Prueba estadística df P
Prueba de log-rango 29723 1 0,0847
Wilcoxon 2,593 1 0,1073
1,00
0,95
0,90
0,85
0,80
0,75
0,70
0,65
0,60
0,55
0,50
1,00
0,98
0,96
0,94
0,92
0,90
0,88
0,86
0,84
0,82
0,80
0,78

29. Figure
Urology Practice 2014 1, 2-6DOI: (10.1016/j.urpr.2014.02.014)
Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions

43. Nuevas drogas en mCPRC