Prostate carcinoma- locally advanced

MANAGEMENT OF
LOCALLY ADVANCED
PROSTATE CANCER
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai
1

MODERATORS:
Professors:
Prof. Dr. G. Sivasankar, M.S., M.Ch.,
Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
Dr. J. Sivabalan, M.S., M.Ch.,
Dr. R. Bhargavi, M.S., M.Ch.,
Dr. S. Raju, M.S., M.Ch.,
Dr. K. Muthurathinam, M.S., M.Ch.,
Dr. D. Tamilselvan, M.S., M.Ch.,
Dr. K. Senthilkumar, M.S., M.Ch.
DEPT OF UROLOGY,GRH ANDKMC,CHENNAI. 2

DEFINITION
Locally Advanced Prostate Cancer(LAPC):
• regional or lymph node involvement without distant
metastasis (T3-4 N± M0), or
• any combination of these.
3
DEPT OF UROLOGY,GRH ANDKMC,CHENNAI.

4

5

Despite the stage migration a/w PSA testing
and growing number of low-stage and organ-
confined tumors, at least 10% of newly
diagnosed CaP cases have LAPC.
6

• Currently, no consensus exists regarding
the optimal management of LAPC.
• Treatment of LAPC by any single modality
is a/w significant risk of recurrent disease.
7

• Serum PSA, Gleason score, and T stage
are more useful together than alone in
predicting final pathological stage.
8

IMAGING IN LAPC
• TRUS(Traditional gray scale): limited ability to improve cancer
staging.
• Largely operator-dependent and cannot differentiate
between T2 & T3 tumours with sufficient accuracy to be
recommended for routine staging.
• Directed biopsy of seminal vesicles or prostate capsule can be
obtained to confirm cT3 disease.
• Candidates for SV biopsy: T stage > 2a and serum PSA > 10
ng/mL, & Positive biopsies from the base of the prostate.
9

• Addition of Color &
Power doppler to
TRUS to improve
sensitivity- still under
investigation.
10

• Endorectal MRI uses a magnetic coil placed
in the rectum to achieve better visualization
of zonal anatomy of the prostate and may
delineate subtle distinctions b/w T2a/b
&T3 disease.
•>3 cores involved with cancer, abnormal
findings on DRE, and PSA >10 ng/mL
undergoing radical prostatectomy, specificity
of MRI in predicting pT3 disease ~ 95%.
•Thus use of MRI may be best limited to 11

NODAL STAGING
• Abdominal CT and mpMRI indirectly assess nodal
invasion by measuring lymph node diameter.
• Drawbacks: Low sensitivity and microscopic invasion
cannot be detected.
• Using a 10-mm threshold, CT or mpMRI sensitivity is <
40%.
• - Currently available most optimal method for N-staging
is open or laparoscopic lymphadenectomy.
- Image guided intraoperative Sentinel Node detection
(experimental).
12

NOVEL
MARKERS
• Traditional clinical and pathologic
parameters are limited in their ability to
accurately predict local tumor extent
before treatment.
• Chromosomal rearrangements involving the
androgen-regulated gene TMPRSS2 and the
ETS family genes are associated with higher
pathologic stage.
13

14

• High risk of recurrence in clinically advanced
disease, both cT3a and cT3b-T4.
• Bone scans are indicated in these + PSA > 20
ng/mL or Gleason score 8 or higher;
• Pelvic CT/MRI is also indicated for cT3-T4
disease or if calculated probability of lymph node
involvement >10%.
15

16

17

TREATMENT
OPTIONS
18

 Reserved for low
volume tumors that can
be completely excised
 With higher risk of
biochemical failure
RP + PLND ADT + RT
Men with high risk prostate cancer including those with
locally advanced disease – significant risk of disease
progression and cancer specific death if left untreated
19
Dept
of
Urology,
GRH
and
KMC,
Chennai.

DEFERRED
TREATMENT
20

RP alone can result in cancer-free survival in at
least half of men at 8 to 10 years despite
clinically advanced disease.
RADICAL
PROSTATECTOMY
21

Use of RP for m/m of LAPC has decreased d/t:
• Recognition that RP alone is insufficient.
• Improved risk assessment & pt.stratification
• Advances in RT delivery
• Recognition that combined modality treatment
(e.g., RT + AD) improved outcomes compared with
monotherapy.
Nevertheless, RP can cure some high-risk
cases, and addition of adjuvant and combined
therapy may further improve outcomes of surgery
alone.
22

• In recent years, there is a renewed interest in surgery for
LAPC.
• Provided that tumour is not fixed to pelvic wall, or
there is no invasion of urethral sphincter, RP is a
reasonable first step in selected low-volume LAPC
cases.
• Extended pLND should be performed in all high-risk
CaP cases, as estimated risk for positive lymph nodes
is 15-40%
23

Most important pathologic criteria predicting prognosis
after RP are,
Gleason score
surgical margin status
presence of non–organ confined disease.
(e.g. extracapsular extension, seminal vesicle invasion,
lymph node involvement)
24

Rationale for RP in patients with cN0
but pathologically confirmed lymph
node invasion (pN1)
• Studies favour completed RP vs. abandoned RP in
patients found to be N+ at the time of surgery.
• RP results in superior survival of patients with pN+
CaP after controlling for lymph node tumour burden
• and frozen sections of lymph nodes intraoperatively
are no longer recommended.
25

• Extended PLND includes removal of nodes overlying
external iliac artery & vein, nodes within obturator
fossa located cranially and caudally to obturator
nerve, and nodes medial and lateral to internal
iliac artery.
• Survival advantage in more extensive
lymphadenectomy noted in many studies, may be due
to elimination of microscopic metastases; but definite
oncologic benefit is lacking.
26

NEOADJUVANT ANDROGEN
DEPRIVATION(NAD):
• NAD therapy before RP in LAPC does not
improve cancer-specific or overall survival.
27

Adjuvant androgen ablation in men with
pN1 disease:
• Combined RP + early adjuvant HT in pN+
CaP achieves a 10-year CSS rate of 80%.
• pN+ after RP, early adjuvant HT
significantly improve CSS and OS in a
prospective randomised trial.
28

• Benefits Vs side effects of long-term HT.
• Follow-up of PSA and delaying initiation of
HT until PSA level rises is an acceptable
option in selected cases with < 2
microscopically involved lymph nodes in
an extended nodal dissection.
29

Neoadjuvant Chemotherapy and
Chemotherapy–Hormonal Therapy:
On the basis of success of taxanes in
hormone refractory prostate cancer, interest
has increased in earlier use of
chemotherapy in high-risk patients or LAPC.
30

• 3-month combination regimen = two 6-week
cycles of ketoconazole and doxorubicin
alternating with vinblastine and estramustine.
• In addition, concurrent AD with an LHRH agonist and
antiandrogen.
• 4 to 6 months of NAD with paclitaxel,
estramustine, and carboplatin androgen-
dependent, high-risk prostate cancer.
• Single-agent docetaxel.
31

Adjuvant Radiation Therapy:
Withholding regional or systemic therapy until
after prostate is removed may,
 prevent delay in time to surgery
 reduce operative morbidity
 identify those men with adverse pathologic
features or evidence of residual disease who
truly need additional therapy.
(thereby avoiding overtreatment in those
with more favorable disease)
32

• Adjuvant radiation therapy improves local
control and reduces biochemical relapse in
selected patients after RP and likely improves
metastasis-free and overall survival.
• Benefit of adjuvant radiation therapy may be
greatest in cases of positive surgical margins.
• Improved outcomes of adjuvant radiation
therapy are associated with dose escalation
(64 Gy).
33

• Men with seminal vesicle invasion who
achieve a low PSA level (<0.3 ng/mL) after
RP or have positive surgical margins:
more favorable group for adjuvant RT.
34

• RT of the prostatic fossa is beneficial in
CaP patients with pN1 after RP, treated
adjuvantly with continuous ADT.
• Optimal field (prostatic fossa only or whole
pelvis) remains unclear.
35

Adjuvant chemotherapy:
Adjuvant chemotherapy after RP in LAPC
should only be considered in a clinical trial.
36

RADIATION THERAPY
37

• In higher-risk patients, improved biochemical
control observed with 81 Gy or more for
EBRT.
• Greatest benefits in the high-risk group
with PSA > 10 ng/mL.
• Intensity-modulated radiotherapy (IMRT), with
or without image-guided radiotherapy (IGRT),
is the gold standard for EBRT.
38

39

40

• In high-risk tumors or LAPC, monotherapy with
RT or permanent interstitial brachytherapy is
inadequate.
• Outcomes improved by combining RT with
AD, often in conjunction with whole- pelvis
irradiation.
41

42

Neoadjuvant Androgen Deprivation and
Radiation Therapy
 Theoretical benefits of AD(LHRH) before RT
in LAPC are:
- ability to reduce target volume
- potential cytotoxic synergy of radiation and hormone manipulation.
 Observations support Neoadjuvant &
concurrent AD with RT, also a benefit of
prolonged AD.
43

• ADT starts either at the onset of RT (for
adjuvant ADT) or 2 or 3 months before (for
neoadjuvant), but concomitant component is
crucial to potentiate RT.
• Long-term ADT, ranging from 2 to 3 years is
recommended for LAPC rather than short term
(6-months).
44

45

Adjuvant Androgen Deprivation and Radiation
Therapy:
• Adjuvant AD after radiation therapy may benefit
those with very high-risk disease.
• Duration of such adjuvant AD is uncertain:
(2 months neoadjuvant+2 months concurrent +/- 24
additional months)
• prolonged AD may be beneficial for high-risk
disease characteristics, including high-stage cancers,
or high pretreatment serum PSA values.
46

Radiation Therapy and Chemotherapy:
• Less well-studied in LAPC.
• Concerns about additive toxicities.
• Estramustine and vinblastine concurrently with
RT (total, 65 to 70 Gy)
• Estramustine-based regimen also
examined with etoposide before and
during definitive RT.
47

FOCAL ABLATIVE THERAPY
• Cryoablation & High-Intensity Focussed
Ultrasound(HIFU).
• Ability to treat local disease within the
prostate by these modalities may play a
role even in LAPC, most likely in
combination with AD or other systemic
therapy.
48

INTERMITTENT ADT
• To minimizing ADT-related morbidity.
• Rx protocol:
- total ADT until PSA level < 4.0 ng/mL between 24
and 32 weeks, after which treatment withheld after 36
weeks.
- PSA level then monitored and treatment
recommended when PSA level reaches either
pretreatment level (when <15 ng/mL) or 15 ng/mL
(when the initial PSA level was higher than that).
49

NEWER DEVELOPMENTS
 assessing novel molecules in the neoadjuvant setting before
RP - enzalutamide, abiraterone, docetaxel, LHRH agonists, anti-
PD-L1, PARP inhibitors (immunotherapy)
 Genomic-driven adjuvant therapies - DECIPHER test to
select ideal candidates for postoperative radiotherapy (predictor of
metastases and recurrence)
 Radio-guided surgery - Incorporation of the PET-PSMA
imaging during surgery, enhance accuracy and helps to remove
all involved lymph nodes.
 3D elastic augmented-reality robotic radical prostatectomy:
- incorporates the MRI images into the robotic console during
surgery
- identifies capsular involvement when performing nerve-sparing
surgery. (improves Local control)
50

GUIDELINES
and
CLOSING THOUGHTS
51

52

53

54

55

56

57

58

Prostate carcinoma- locally advanced

More Related Content

What's hot (20)

Similar to Prostate carcinoma- locally advanced (20)

More from GovtRoyapettahHospit (20)

Recently uploaded (20)

Prostate carcinoma- locally advanced