Localized & Locally Advanced Carcinoma Prostate

1. LOCALISED & LOCALLY ADVANCED
PROSTATE CANCER
By Dr. Zohaib

2. SCREENING AND EARLY DETECTION OF CAP
Do not subject men to PSA testing without counselling them on the potential
risks and benefits.
Offer early PSA testing to well-informed men at elevated risk of having CAP:
• men > 50 years of age;
• men > 45 years of age and a family history of CAP;
• men of African descent > 45 years of age;
• men carrying BRCA2 mutations > 40 years of age.
Stop early diagnosis of CAP based on life expectancy and performance
status; men who have a life-expectancy of < 15 years are unlikely to benefit.

3. CLINICAL DIAGNOSIS
Prostate cancer is usually suspected on the basis of DRE and/or PSA
levels. Definitive diagnosis depends on histopathological verification
of adenocarcinoma in prostate biopsy cores.
Most CAP are located in the peripheral zone and may be detected by
DRE when the volume is > 0.2 mL.
In ~18% of cases, PCa is detected by suspect DRE alone, irrespective
of PSA level.

4. CONTD..
PSA is organ specific but not cancer specific.
As an independent variable, PSA is a better predictor of cancer than
either DRE or transrectal ultrasound (TRUS).
To avoid unnecessary biopsies, offer further risk-assessment to
asymptomatic men with a normal digital rectal examination and a
prostate-specific antigen level between 2-10 ng/mL prior to
performing a prostate biopsy. Use one of the following tools:
• risk-calculator;
• imaging;

5. THE ROLE OF IMAGING IN CLINICAL DIAGNOSIS
TRUS is not reliable at detecting CAP and the diagnostic yield of
biopsies performed on hypoechoic lesions is negligible.
Multiparametric magnetic resonance imaging performance in
detecting ISUP grade > 2 CAP correlation with RP specimens shows
that mpMRI has good sensitivity for the detection and localisation of
ISUP grade > 2 cancers.
Do not use multiparametric magnetic resonance imaging (mpMRI) as
an initial screening tool.
It should be performed before prostate biopsy.

6. CONTD..
In biopsy naïve patients
When mpMRI is positive (i.e. PI-RADS > 3), combine targeted and
systematic biopsy.
In patients with prior negative biopsy
When mpMRI is negative (i.e. PI-RADS < 2), and clinical suspicion of
prostate cancer is high, perform systematic biopsy based on shared
decision making with the patient.

7. CONTD..
Transrectal prostate needle biopsies are performed under antibiotic
protection and use a local anaesthetic by peri-prostatic infiltration for
prostate needle biopsies.
Ensure that prostate core biopsies from different sites are submitted
separately for processing and pathology reporting.
Low-risk localised disease
Do not use additional imaging for staging purposes.
High-risk localised disease/locally advanced disease
Perform metastatic screening including at least cross-sectional
abdominopelvic imaging and a bone-scan.

8. EVALUATION OF LIFE EXPECTANCY AND
HEALTH STATUS
Use individual life expectancy, health status,
and comorbidity in CAP management. Strong
Use the Geriatric-8 and mini-COG tools for
health status screening. Strong
Perform a full specialist geriatric evaluation
in patients with a G8 score < 14.
Offer symptom-directed therapy alone to
frail patients.
Median Life Expectancy is predicted by Age
and Gait Speed for males

9. CLINICAL TUMOR NODE METASTASIS (TNM)
CLASSIFICATION OF PROSTATE CANCER

10. PRETREATMENT RISK ASSESSMENT

11. TREATMENT MODALITIES
•Active surveillance/Watchful waiting
•Radical Prostatectomy – Open (Retropubic/Perineal),
Laparoscopic, Robot-assisted laparoscopic
•Radiotherapy – ERBT, Brachytherapy
•Cryotherapy
•High intensity focused Ultrasound (HIFU)
•Hormonal Therapy

12. ACTIVE SURVEILLANCE/WATCHFUL WAITING
Deferred treatment
[In localised disease a life expectancy of at least 10 years is considered
mandatory for any benefit from local treatment].
Definitions of active surveillance and watchful waiting

13. T
RADICAL PROSTATECTOMY
RETROPUBIC ADVANTAGES:
Whole prostate and thus the entire tumor can be examined
histologically.
Surgeon has access to regional lymph nodes to test if prostate cancer
cells have left the tumor.
Surgical margin can be examined.
Complications are Incontinence, Impotency, bladder neck contracture,
Bleeding, Thrombo-embolism.
Negative
Surgical
Margin
Positive
Surgical
Margin
OR
T Not all
of tumor
removed

14. RETROPUBIC APROACH
Excision of entire prostate along with
its intact capsule, prostatic urethra &
seminal vesicles.
Usually epidural anesthesia.
Incision: Lower midline staying
extraperitoneal, the retropubic space is
opened.
Remaining Urethra is sewn to bladder.
neck over a catheter.
Recent studies showed performing
PLND during RP failed to improve
oncological outcomes, including
survival.
Bladder
Prostate
Urethra
Rectum
Surgical
Approach
Pelvic
Bone
(Pubis)

15. PERINEAL APROACH
Very similar to Retropubic protocol
(nerve sparing, sewing of urethra,
etc.)
Incision:
Between Anus and base of Scrotum.
Disadvantages:
Cannot access regional lymph nodes
Slight increase in risk of rectal injury
and associated complications.
Bladder
Prostate
Urethra
Rectum
Surgical
Approach
Pelvic
Bone

16. Laparoscopic RP Robot-assisted
Laparoscopic RP

17. RADIOTHERAPY – EXTERNAL BEAM
Intensity-modulated radiotherapy (IMRT), with or without image-guided
radiotherapy (IGRT), is the gold standard for EBRT.
Map precise area that will receive radiation.
Multiple treatments ~5 days/week for 6~8 weeks. Each treatment takes
about 10 minutes and no anesthesia is required.
Seminal
Vesicles
Prostate

18. BRACHYTHERAPY
40-100 rice-sized radioactive seeds are implanted into the prostate
via ultrasound-guided needles. Anesthesia is required.
All radiation inside the pellets is generally exhausted within a year.
Image of Prostate
With Radioactive
Bead Implants

19. CRYOTHERAPY & HIFU
[Two minimal invasive treatment for organ confined recurrent disease
following radiotherapy]
CRYOTHERAPY
Destroys tissue by freezing tissue at -40°c through trans-perineal u/s
cryo-probe deliver Argon or liquid nitrogen. It induces cell death by
dehydration.
High intensity focused ultrasound (HIFU);
It is the selective destruction of tissues at 85°c by using trans-rectal
device that causes coagulative necrosis.

20. HORMONAL THERAPY
Prostate cells and prostate cancer cells are dependent upon
androgens (male sex hormones) for survival and growth.
Removal of androgens kills a majority of prostate cancer cells.
Testes
Prostate
Growth and
Function
Testosterone
95%
Adrenal
Androgen
5
%

21. CONTD..
Surgical Castration - Bilateral orchiectomy, or subcapsular
pulpectomy (PSA levels <20ng/dl usually achieved)
Medical Castration – LHRH agonists (Leuprolide, triptorelin), LHRH
antagonists, Estrogen
Anti-Androgens – steroidal (cyproterone acetate) and non-steroidal
(flutamide and bicalutamide).
New Compounds – Abiraterone (intracellular testosterone
suppressor), Enzalutimide (higher affinity for the AR receptor than
bicalutamide).

22. ACTIVE TREATMENT
Inform patients that no active treatment modality has shown
superiority over any other active management options or deferred
active treatment in terms of overall- and prostate cancer-specific
survival for clinically localised disease.
Offer a watchful waiting policy to asymptomatic patients with a life
expectancy < 10 years (based on comorbidities).
Inform patients that all active treatments have side effects.

23. CONTD..
When a lymph node dissection (LND) is deemed necessary, perform
an extended LND template for optimal staging.
Do not offer neoadjuvant androgen deprivation therapy before
surgery.
Radiotherapeutic treatment
Offer intensity-modulated radiation therapy (IMRT) or volumetric arc
external-beam radiotherapy (VMAT) for definitive treatment of PCa by
external-beam radiation therapy.
Active therapeutic options outside surgery and radiotherapy
Only offer cryotherapy and high-intensity focused ultrasound within a
clinical trial setting or well-designed prospective cohort study.

24. TREATMENT
OF LOW
RISK
DISEASE

25. TREATMENT
OF
INTERMEDIATE
RISK DISEASE

26. RADICAL
TREATMENT
OF HIGH
RISK
DISEASE

27. RADICAL
TREATMENT
OF LOCALLY-
ADVANCED
DISEASE

28. ADJUVANT TREATMENT OPTIONS AFTER
RADICAL PROSTATECTOMY
Do not prescribe adjuvant androgen deprivation therapy (ADT) in pN0
patients.
Offer adjuvant external-beam radiation therapy to the surgical field
to highly selected patients.
Discuss three management options with patients with pN+ disease
after an extended lymph node dissection, based on nodal
involvement characteristics:
1. Offer adjuvant ADT;
2. Offer adjuvant ADT with additional radiotherapy.

29. NON-CURATIVE OR PALLIATIVE
TREATMENTS IN PROSTATE CANCER
Watchful waiting (WW) for localised prostate cancer
Offer WW to asymptomatic patients not eligible for local curative
treatment and those with a short life expectancy.
Watchful waiting for locally advanced prostate cancer
Offer a deferred treatment policy using androgen deprivation (ADT)
monotherapy to M0 asymptomatic patients with a prostate-specific
antigen (PSA) doubling time > 12 months, a PSA < 50 ng/mL and
well-differentiated tumor, who are unwilling or unable to receive any
form of local treatment.

30. MANAGEMENT OF PERSISTENT PSA AFTER
RADICAL PROSTATECTOMY
Offer a prostate-specific membrane antigen positron emission
tomography (PSMA PET) scan to men with a persistent PSA > 0.2
ng/mL to exclude metastatic disease.
Perform PSMA PET/CT (if available) or fluciclovine PET/CT or choline
PET/CT in patients fit for curative salvage treatment.

31. SECOND-LINE THERAPY AFTER TREATMENT
WITH CURATIVE INTENT
Recommendations for biochemical recurrence after radical
prostatectomy
Offer salvage radiotherapy (SRT) to patients with a PSA rise.
Once the decision for SRT has been made, SRT (at least 66 Gy)
should be given as soon as possible.

32. CONTD..
Recommendations for biochemical recurrence after radiotherapy
Only offer salvage high intensity focused ultrasound, salvage
cryosurgical ablation and salvage brachytherapy to patients with
proven local recurrence within a clinical trial setting or well-
designed prospective cohort study.
Recommendations for systemic salvage treatment
Do not offer androgen deprivation therapy to M0 patients with a
PSA-doubling-time > 12 months.

33. FOLLOW-UP
After treatment with curative intent:
Routinely follow up asymptomatic patients by obtaining at least a disease-
specific history and serum prostate-specific antigen (PSA) measurement.
These should be performed at 3, 6 and 12 months after treatment, then
every 6 months until 3 years, and then annually.
At recurrence, only perform imaging to detect local recurrence if the
outcome will affect treatment planning.
Only offer bone scans and other imaging modalities to men with biochemical
recurrence or symptoms suggestive of progression without signs of
biochemical relapse.

34. QUALITY OF LIFE IN MEN UNDERGOING LOCAL TREATMENTS
It is advisable to eligible patients for active surveillance, that global
quality of life is equivalent for up to 5 years compared to radical
prostatectomy or external beam radiotherapy.
It should be discussed that the negative impact of surgery on urinary
and sexual function, as well as the negative impact of radiotherapy on
bowel function with patients.