Pautas generales de manejo de cáncer de próstata

1. CES2019-02: Cáncer de próstata
Mauricio Lema Medina MD

2. Most common non-cutaneous
malignancy in men in North
America
2nd most common cause of
cancer-related deaths in men
1 in 7 men will be diagnosed
Lifetime risk of being diagnosed
with prostate cancer is 18/100 but
risk of dying of prostate cancer is
only 3/100

3. Risk factors
Established
Advancing age
Presence of androgens
Family history 1st degree
relative
African ancestry

4. RISK FACTORS
Potential
High dietary fat
Obesity
Inherited mutations (BRCA1 or
BRCA2 genes)
Vitamin D or E deficiency
Selenium deficiency?

5. Early stages usually asymptomatic
Most cases detected by serum PSA
screening
Palpable nodule or firmness on DRE
Advanced stages
Urinary retention/renal failure
Bone pain
Anemia
Weight loss, fatigue
Spinal cord compression

6. SCREENING
Goal
To identify the presence of
disease at a stage when
treatment can be given that
will cure it
Use a combination of DIGITAL
RECTAL EXAMINATION (dre) and PSA

7. DRE (digital rectal exam)
has a 50/100 positive
predictive value
DRE alone is not a good
screening tool
BUT it is an
important part
of screening

8. A Serine protease
(enzyme) found in
the prostate
Secreted by
prostate
epithelial cells
Found in ejaculate
As diagnostic tool
for:
Screening
Staging
Prognostic
indicator
Surveillance
PROSTATE SPECIFIC ANTIGEN (PSA)

9. SCREENING WITH PSA
No clear cut-point between normal and abnormal PSA levels. Even
PSA cut-off of 1.1 ng/ml misses up to 15% of prostate cancer (The
Cancer Prevention Trial – 2003)
Positive predictive value for PSA > 4ng/ml = 30% (i.e. About 1 in 3
men with elevated PSA have prostate cancer detected at time of
biopsy
PPV increases to 45-60% for PSA > 10ng/ml
Nearly 75% of cancers detected in the grey zone (PSA 4-10) are
organ confined; potentially curable.
<50% of prostate cancers organ confined if PSA >10

10. SCREENING WITH PSA
Pros
 Early detection of disease leads to higher cure rates
 By the time symptoms of prostate cancer present usually not curable
 Screening offers a modest effect on mortality
 The “number needed to screen” is similar to studies on
mammography for Breast Ca and fecal occult blood testing for Colon
Cancer
Cons
 If tests abnormal, need for prostate biopsy
 If cancer found & treatment chosen, morbidity from therapy
 If insignificant cancer found, treatment was unnecessary
 Risk of overdiagnosis, overtreatment

11. SCREENING WITH PSA:
RECOMMENDATIONS
Discuss with the patient and if he decides to be
screened
Annual PSA and DRE
Age 50-70 yrs (with at least 10 yr life expectancy)
Begin screening at age 40 if risk factors
African ancestry
First degree relative(s) with prostate cancer
A shared decision-making approach to PSA screening
seems most appropriate

12. Page  12

13. Biología del cáncer de próstata

14. Fusión TMPRSS2-ERG
• En hasta 80% de los cánceres de próstata
• ERG es un factor de transcripción
– Proliferación
– Fenotipo resistente a la castración
• TMPRSS2 es un gen que responde al AR
– Es una serina proteasa
• Es una diana molecular potencial
– El silenciamiento ERG con RNAi disminuye
proliferación

15. Prostate cáncer diagnosis
Indications for transrectal ultrasound (TRUS)
guided biopsy
Palpable nodule on DRE
Elevated serum PSA
Biopsy involves 10-18 needle cores taken mostly
from the peripheral zone of the prostate
Transrectal ultrasound alone/CT scan/MRI not
sensitive enough to make the Diagnosis

16. Enfoque diagnóstico – Cáncer de
Próstata
Enfoque
diagnóstico –
cáncer de
próstata
Síntomas
urinarios o
PSA anormal
Evaluación
rectal digital
(DRE) / PSA
(si falta)
DRE: Normal
PSA: Normal
PSA de 2, o
menos
PSA de 2+
Velocidad PSA
0.75+/año
TRUB
Repetir 1-3
años
DRE: Anormal
o
PSA: Anormal
TRUB
PSA 10, o menos
+ PSA libre 15%
o menos
Repetir en 6
meses
TRUB: Biopsia transrectal eco-dirigida
PSA: Antígeno específico de próstata
No
Si
No
PSA 10+

17. - histology:
- Gleason scores

18. Prostate cáncer pathology
Adenocarcinoma
Gleason “grade” is from 1-5
based on glandular
architecture
Gleason score is the total
primary grade (1-5) +
secondary grade (1-5) = 2-10
 4-6/10=well-differentiated
 7/10=moderately differentiated
 >8/10=poorly differentiated

19. Gleason 6
www.cancernetwork.com - Cesar A Moran, 07.02.2014

20. Gleason 7
www.cancernetwork.com - Cesar A Moran, 07.02.2014

21. Gleason 8
www.cancernetwork.com - Cesar A Moran, 07.02.2014

22. Gleason 9
www.cancernetwork.com - Cesar A Moran, 07.02.2014

23. PATHOLOGY GROUPINGS IN PROSTATE
CANCER
• GROUP 1
– Gleason score 3+3, or less.
• GROUP 2
– Gleason score 3+4
• GROUP 3
– Gleason score 4+3
• GROUP 4
– Gleason total score 8
• GROUP 5
– Gleason total score 9 or 10

24. Prostate cáncer staging
Can spread to adjacent organs (seminal
vesicles, bladder), lymph nodes, bone
Most bone mets are osteoblastic
Prior to initiating treatment consider
Bone scan (PSA>10, Gleason Score >7)
CT scan pelvis/abdomen (PSA >10, Gleason
Score >7))
These tests are typically not required in
asymptomatic men with low risk prostate
cancer

25. Maniobras de estadificación
• Consideraciones
– Tumores MUY tempranos pueden no necesitar estudios
adicionales para metástasis a distancia
• T1c/T2a; PSA de 10, o menos; Gleason 6, o menos.
• RM de próstata con antena rectal – para planeación terapia
– Tumores MUY avanzados pueden ser investigados con:
• Gammagrafía ósea / TAC de tórax, abdomen y pelvis
– Tumores POTENCIALMENTE avanzados pueden beneficiarse de:
• RM corporal total
• El PET-CT es ineficaz en cáncer de próstata
– Tumores candidatos a terapia local (Prostatectomía /
Braquiterapia) o candidatos a Radioterapia
• RM Multiparamétrica de próstata con antena rectal

26. Práctica usual
• Gammagrafía ósea
• TAC de tórax contrastado
• RM de pelvis / Próstata con antena rectal
• PSA

27. Carcinoma de Próstata
TNM
• T1 - Tumor primario no aparente clínicamente ni visible por imágenes.
T1a - Hallazgo incidental que compromete <= 5% del tejido resecado.
T1b - Hallazgo incidental que compromete > 5% del tejido resecado.
T1c - Diagnóstico obtenido por biopsia ciega inducida por un PSA
elevado.
• T2 - Tumor confinado a la próstata.
T2a - Compromete sólo un lóbulo de la próstata.
T2b - Compremete ambos lóbulos de la próstata.
• T3 - Tumor que se extiende más allá de la cápsula prostática.
T3a - Extensión extracapsular.
T3b - Invade la vesícula seminal.
• T4 - Fijado a otras estructuras distinto a las vesículas seminales.
• N1 - Ganglios linfáticos comprometidos.
• M1 - Metástasis a distancia.
M1a - Ganglios linfáticos no regionales.
M1b – Huesos.
M1c - Otros sitios.

28. Carcinoma de Próstata
Clasificación por etapas
• Estadío I: T1a de bajo grado N0 M0;
• Estadío II: T1a de alto grado-T2 N0 M0;
• Estadío III: T3 N0 M0;
• Estadío IV: T4 N0 M0, Cualquier T N1
M0, Cualquier T Cualquier N M1.

29. Very low risk (must fulfill all)
T1c
Grade Group 1
PSA less than 10
Less than 3 core+, with less
than 50 per-cent cancer in
each
Psa density less than 0.15

30. low risk (must fulfill all)
T1-T2a
Grade Group 1
PSA less than 10

31. Favorable intermediate
T2b-T2c or
Grade Group 2 or
PSA 10-20 and
positive biopsy cores less 50
per-cent

32. unfavorable intermediate
T2b-T2c or
Grade Group 2 or group 3 or
PSA 10-20

33. high
T3a or
Grade Group 4 or group 5 or
PSA greater than 20

34. VERY high
T3b-t4 or
Grade group 5 or
More than 4 cores with grade
group 4 or 5

36. Prostate cáncer treatment
Considerations
Patient’s age
Co-morbid health conditions
Tumor stage
Tumor grade (Gleason score)
Often a patient choice
Surgery and

37. Early stage Prostate cáncer
treatment
Early stage Cancer
1. Radical Prostatectomy
2. External Beam Radiotherapy
3. Radioactive Seeds (Brachytherapy)
4. Active Surveillance
5. Observation – Watchful Waiting

38. Early stage Prostate cáncer
treatment: radical prostatectomy
Radical Prostatectomy
Complete surgical removal of entire prostate,
seminal vesicles
Considered a good treatment for men <70
years of age with clinically organ confined
cancer who are healthy
Open or laparoscopic/robotic approaches

39. Early stage Prostate cáncer
treatment: radical prostatectomy

40. radical prostatectomy:
complications
<10% risk of blood transfusion
Wound infection
Rectal injury (<1%)
Urinary incontinence (~10%)
Erectile dysfunction (variable but common)
Anesthetic related

41. Prosate cancer treatment:
radiotherapy
Radiotherapy Options
External Beam
Brachytherapy (seed implant)
Concept of maximizing dose to the tumor and
minimizing collateral damage
Curative options for patients at high risk for
morbidity from radical prostatectomy
Age, medical co-morbidities
Patient preference

42. Prosate cancer treatment:
radiotherapy

43. Radiotherapy: complications
External Beam Radiation Therapy
Hematuria
Radiation proctitis
Loose, bloody stools
Urinary retention
Strictures (urethra and ureter)
Erectile dysfunction
Secondary malignancies
Bladder, rectal, hematological

44. Proctitis Actínica

45. Prostate cancer therapy:
brachytherapy

46. Brachytherapy: complications
Urethral strictures
Seed migration
Urinary retention
Erectile dysfunction
Irritative voiding symptoms

47. Active surveillance
Observing low grade tumors in men <70 yrs and >10 yr
life expectancy
Delay definitive treatment until it is necessary and
cancer is still curable
Goal is to delay potential treatment-related morbidity
Monitor DRE, PSA, and periodic repeat biopsy
Ideal candidate:
 PSA < 10
 Normal DRE
 Gleason <7 (low grade)
 Only 1-3 / 12 biopsy cores positive

48. Watchful waiting
Observing low grade tumors in men
>70 yrs or <10 yrs life expectancy
Institute hormonal therapy when
patient becomes symptomatic
No curative intent

49. Treatment options by risk
1/2
Risk Group
Very-low risk
Active surveillance
External-Beam Radiotherapy
Radical prostatectomy +/- RPLND
Observation
Low risk
Active surveillance
External-Beam Radiotherapy
Radical prostatectomy +/- RPLND
Observation
Favorable intermediate
Active surveillance
External-Beam Radiotherapy
Radical prostatectomy +/- RPLND
Observation
RPLND: Retroperitoneal Lymph-Node Dissection

50. Treatment options by risk
2/2
Risk Group
Unfavorable intermediate risk
External-Beam Radiotherapy + ADT (4 mo)
Radical prostatectomy +/- RPLND
Observation
High risk
External-Beam Radiotherapy + ADT (18 mo)
Radical prostatectomy + RPLND
Very High risk
External-Beam Radiotherapy + ADT (18 mo)
Radical prostatectomy +/- RPLND
RPLND: Retroperitoneal Lymph-Node Dissection

51. Position statement: Non metastastic prostate cancer
Mauricio Lema - 2014
Watchful waiting and Active
Surveillance are NOT without
side-effects. Recommendations
need to be INDIVIDUALIZED
RP or RT or Active Surveillance (AS) or Watchful Waiting
(WW), or Brachytherapy (BT)*
Localized Low-Risk
T1c-T2a
PSA 10, or less
Gleason 6, o less
AS: Prostate US/PSA q3 Mo; Biopsy if
indicated. Treatment if progression.
WW: PSA q6 Mo, treatment if indicated
65 yo, or less: RT, RP or AS
Adverse features
PSA velocity 2+/year
50%+ positive findings in biopsy
Perineural invasion
Adverse features: active
treatment (RT, RP or BT)
*BT if feasible
Low risk
Small tumors
Adequate anatomy

52. Position statement: Non metastastic prostate cancer
Mauricio Lema - 2014
Radiation (RT) + LH-RH/Antiandrogen x6-24 Mo+ Mo
Locally-Advanced
(T3/T4)
Localized High-
Risk
T2c
PSA 20+
Gleason 8+
RT + LH-RH/Antiandrogen x4 Mo or RP
Localized
Intermediate-Risk
T2b
PSA 10-20
Gleason 7
Antiandrogen for at least 1 Mo
Antiandrogen for at least 1 Mo
“Would NOT use hormonal therapy in patients with known
coronary artery disease, unless benefit clearly outweigh risk”
RT + LH-RH/Antiandrogen x6-24 Mo or Radical
prostatectomy (RP)
Antiandrogen for at least 1 Mo
RP or RT or Active Surveillance (AS) or
Watchful Waiting (WW), or Brachytherapy
Localized Low-Risk
T1c-T2a
PSA 10, or less
Gleason 6, o less
AS: Prostate US/PSA q3 Mo; Biopsy if
indicated. Treatment if progression.
WW: PSA q6 Mo, treatment if indicated

53. Advanced or metastatic prostate
cancer
Not curable disease
Goals shift to disease control
Development of cancer cells unresponsive
to androgen deprivation
Typically occurs slowly over time, although
it can occur rapidly

54. Treatment strategies for
metastatic prostate cancer
Androgen Deprivation (Hormonal Rx)
Orchidectomy
LHRH analogues
Antiandrogens
Supportive therapies
Analgesics
Steroids
Bisphosphonates/Vitamin
D/Calcium for bone health
Chemotherapy
 Taxotere, Docetaxel
Last line of treatment