Focal therapy aims to eradicate significant prostate cancer while minimizing side effects to preserve gland function. Accurate localization of tumors is important and is achieved through multiparametric MRI and biopsy. Cryotherapy, high-intensity focused ultrasound, photodynamic therapy, and radiofrequency ablation are ablative technologies used in focal therapy. Factors like freezing speed and thaw cycles impact cryotherapy's effectiveness. Follow-up is best with MRI-ultrasound fusion to assess treatment response.

1. Supervised By Dr. Yousif M. Al-Hallak
Presented By Dr. Mohammed A. Al-Saffar

2. Prostate Cancer
 In the United States, prostate cancer
 is the most common visceral malignancy in men.
 is the second leading cause of cancer-related deaths.
 Worldwide, prostate cancer incidence and mortality rates:
 vary significantly between countries and regions.
 are highest in African-American and Jamaican men.
 PSA screening has induced a significant downward
migration in age and stage (both clinical and pathologic)
at diagnosis.

3. Prostate Cancer
 PSA screening may have a beneficial effect on prostate
cancer mortality; however, the absolute effect is small
relative to the number needed to screen and treat to cure a
single individual.
 Because of effective treatment of some prostate cancers
and the biologic indolence relative to life expectancy,
only about 16% of men diagnosed with prostate cancer
ultimately die of it

4. Local & Locally Advanced Ca Prostate
 In localized prostate cancer, the cancer has not spread
outside the prostate.
 In locally advanced prostate cancer: cancer that has
started to break out of the prostate, or has spread to the
area just outside the prostate, but not to distant sites, such
as lymph nodes or bones.
• Prostate capsule,
• Seminal vesicles,
• Bladder
• Rectum

7. How is prostate cancer diagnosed?
 There is no test that can diagnose local or locally
advanced prostate cancer on its own. Prostate cancer is
diagnosed using the results of some or all of the following
tests.
 PSA test
 Digital rectal examination (DRE)
 Prostate biopsy
 MRI scan or CT scan
 Bone scan

8. Identifying The Patient Population For Focal
Therapy
 Any man with localized prostate cancer suitable for
curative therapy should be regarded as suitable for
some form of focal therapeutic intervention.
 The arguments for focal therapy to be carried out only
in men suitable for active surveillance are
 (1) reduction of the potential psychological morbidity
associated with men not having treatment for a cancer,
“some form of treatment is better than none,”
 (2) reduction of the surveillance of cancer progression
rate (about one third require delayed intervention
within 5 yrs).

9. Evaluation of the Patient
 A radionuclide bone scan, abdominal-pelvic computed
tomography (CT) scan, and magnetic resonance
imaging (MRI) scan are not indicated if the tumor has a
 Gleason sum of less than 7 (or in some guidelines, 8)
(NCCN, 2014),
 the serum PSA level is less than 10 ng/mL, and
 the biopsy findings do not reveal an extensive or highly
aggressive cancer, because the likelihood of finding
metastases is quite low.

11. Localization of Disease
Imaging: Advances in Ultrasound
 Increased vascularity or changes in blood flow are an important
feature of prostate cancer and have been associated with higher
Gleason grades (Wilson et al, 2004; Heijmink et al, 2006).
 Contrast-enhanced transrectal ultrasonography (CETRUS)
involves detecting the difference in acoustic impedance
between the contrast agent and adjacent tissue (Jakobsen et al,
2001).
 Elastography demonstrates the higher cell and vessel density in
prostate cancer based on increased stiffness in comparison to
the surrounding normal tissue

12. Localization of Disease
Multiparametric Magnetic Resonance Imaging
 mpMRI involves different imaging parameters including
T2-weighted imaging (T2W), dynamic contrast-enhanced
(DCE) imaging, diffusion-weighted imaging (DWI), and
magnetic resonance spectroscopy (MRS).
 MRI-TRUS image fusion– targeted biopsies detect
more clinically significant cancers using fewer cores
compared with standard biopsy techniques.

13. PI-RADS score
 The European Society of Urogenital Radiology (ESUR)
proposed a numeric system called the Prostate Imaging
Reporting and Data System, or PI-RADS, for prostate
cancer detection.
 the four commonly used parameters:
1. T2 weighted images give excellent anatomic detail
2. Diffusion-weighted imaging (DWI) gives functional
information about the movement of water molecules,
which is different in healthy tissue than in tumors.

14. PI-RADS score
3. Dynamic contrast-enhancement (DCE) can point to a
tumor by revealing abnormal blood flow from network of
abnormal blood vessels that feed the tumor (angiogenesis)
4. MRI spectroscopy (MRS) is used to show concentrations
of metabolites, since the presence of certain metabolites
characterizes prostate cancer.

15. PI-RADS score
 It is based on a score from 1 to 5 but there are two levels to the
system.
Level One: Each parameter that shows up in an image (T2, DWI,
DCE and MRS) is assigned a numerical value, with 1 being
most probably benign and 5 being highly suspicious of
malignancy.
Level Two: The values are added together. In centers that don’t
analyze for MRS, only T2, DWI and DCE are added together.
In centers that analyze for all four parameters, those values are
summed.
 The total determines whether the PI-RADS classification is
Level I, II, III, IV, or V. The table below shows the probability
range from benign to highly suspicious for cancer.

17. Localization of Disease
 Focal therapy requires accurate localization of disease to
drive precision ablation.
 Localization of disease requires histology and imaging,
either alone or in combination,
 An accurate localization strategy will more clearly define
the patient population in terms of stage, grade, and
disease burden.
 Most studies have a widely used definition of clinically
significant prostate cancer of 0.5 mL or greater in
volume and/or Gleason grade 3+4 or higher.

18. Localization of Disease
Biopsy
 the role of prostate biopsy is not only in cancer diagnosis
but also in characterization and localization of individual
lesions
 Systematic Transrectal Ultrasound–Guided Biopsy
 Transrectal Saturation Biopsy
 Transperineal Saturation Biopsy
 Transperineal Template Prostate Mapping Biopsy

19. Grade Groups
In 2014, the International Society of Urological Pathologists
released supplementary guidance and a revised prostate cancer
grading system, called the ISUP Grade Groups.

20. Risk Stratification
 Low risk: Tumor is confined to the prostate, and the PSA
is <10 and grade group 1 (Gleason 6). There is also a
subset of extremely “slow-growing” tumors called “very
low risk” in which fewer than 3 biopsy tissue samples
contain cancer cells and the cancer is not detectable by
DRE.
 Intermediate risk: Tumor is confined to the prostate, the
PSA is between 10 and 20, or grade group 2 or 3 (Gleason
7). This category is often divided into a “favorable” and
“unfavorable” intermediate risk.

21. Risk Stratification
 High risk: Tumor extends outside the prostate, the PSA
>20, or grade group 4 or 5 (Gleason 8 to 10). There is also
a subset of very aggressive tumors is called “very high
risk” in which the tumor has extended into the seminal
vesicles (T3b) or the rectum or bladder (T4), or there are
multiple biopsy samples with high grade cancer.

22. Management of low-risk disease
Active surveillance:
 This is the preferred management option in low-risk
patients with the understanding that curative treatment
will be offered if follow-up demonstrates either worrisome
PSA elevation or worsening biopsy characteristics (e.g.
Gleason grade and or/volume changes)

23. Management of low-risk disease
Treatment options:
 Radical treatment is not appropriate for patients with a life
expectancy of <10 years.
 Radical prostatectomy.
 Low dose rate (LDR) Brachytherapy
• Patients with a prior transurethral resection (TURP)
should be assessed on an individual basis.
• Patients with significant baseline obstructive symptoms
may not be eligible for brachytherapy (i.e. American
Urological Association symptom score >20).

24. Management of low-risk disease
 External beam radiotherapy
 3D-conformal radiotherapy or intensity modulated radiation
therapy (IMRT) should be utilized to deliver an International
Commission on Radiation Units (ICRU) dose to the prostate of
74-78 Gy in 1.8-2.0 Gy fractions .
 Hypofractionated radiation (e.g. 60 Gy in 20 fractions) may be
considered.
 Cryosurgery
 There is less long-term data for efficacy and toxicity compared
to the other treatment modalities.
 High intensity focused ultrasound (HIFU).

25. Management of intermediate-risk disease
Treatment options:
 Radical prostatectomy plus bilateral pelvic lymph
node dissection.
 External beam radiotherapy
 Brachytherapy
 Cryosurgery

26. Management of high-risk disease
Treatment options:
 EBRT + ADT
 Radical prostatectomy and pelvic lymphadenectomy
 Cryosurgery

27. Ablative Technology

28. Ablative Technology
Cryotherapy
 ablation of tissue by extremely cold temperatures.
1. Direct cytolysis through extracellular and intracellular ice
crystal formation
2. Intracellular dehydration and pH changes
3. Ischemic necrosis via vascular injury
4. Cryoactivation of antitumor immune responses
5. Induction of apoptosis
6. Endothelial damage, which leads to platelet aggregation and
microthrombosis
7. Injury that occurs during warming as a result of osmotic
cellular swelling and vascular hyperpermeability

30. Ablative Technology
Cryotherapy
 number of factors affect the efficiency of tissue
destruction, namely:
 1. Velocity of cooling
 2. Nadir temperature
 3. Freezing duration
 4. Velocity of thawing
 5. Number of freeze-thaw cycles
 6. Presence or absence of large blood vessels, which can
act as heat sinks

31. Ablative Technology
Cryotherapy
 Histopathologic changes after cryotherapy in the prostate
are divided into an
 early degenerative phase caused by coagulative necrosis
and a
 later phase of repair—fibrosis, calcification, and
hyalinization

33. Ablative Technology
High-Intensity Focused Ultrasound
 mechanical vibrations above the threshold of human
hearing (16 kHz) and has the ability to interact with tissue
to produce biologic changes
 Histologically, the tissue changes that occur are
homogeneous coagulative necrosis, with an inflammatory
response leading to formation of granulation tissue —
indicated by the presence of immature fibroblasts and new
capillary formation—at the periphery of the necrotic area
about a week after treatment.

35. The Sonablate high-intensity focused ultrasound
transrectal probe has two focal lengths: 3 cm and 4 cm.

37. Ablative Technology
Photodynamic Therapy
 uses a photosensitizing drug that is activated, after a given
drug-light interval, by light of a specific wavelength. It
requires tissue oxygen for the treatment effect, with the
activated drug forming reactive oxygen species, which
are directly responsible for damage to the treated volume.
 These drugs usually take a long time to be cleared and can
accumulate in the skin, requiring patients to be covered
from sunlight (cause a sunburn-like reaction) for a few
weeks.

38. Ablative Technology
Focal Photothermal Therapy
 uses laser fibers with the objective to raise the temperature
directly in the treatment area. No photosensitizing agent
nor oxygen tissue supply are needed.

39. Ablative Technology
Focal Irreversible Electroporation
 causes tissue damage by permanently altering the cell
homeostasis using low-energy direct current.
 The use of low voltage avoids local thermal effects and
instead forms nanopores in the cellular membrane, which
lead to cell death.

41. Ablative Technology
Radiofrequency Ablation
 acts by converting radiofrequency waves to heat, resulting
in thermal damage. High-frequency current flows from
the needle electrode to target tissue with resultant ionic
agitation and heat-producing molecular friction,
denaturation of proteins, and cell membrane
disintegration.

43.  Q1. what is / are the aims of focal therapy in the treatment
of Ca prostate?
 A. to increase cancer specific and overall survival
 B. to eradicate significant disease and minimize side effect
 C. to maintain oncological benefits with respect to active
treatment
 D. to preserve function of the gland
B

44.  Q2. which answer is correct for focal HIFU in prostate
cancer?
 A. TURP is necessary prior to focal HIFU
 B. focal HIFU is best suited for ant. Lesions in the
prostate.
 C. focal one device enable immediate post treatment
contrast enhanced US
 D. focal HIFU is associated with a high rate in the bladder
neck sclerosis
C

45.  Q3. proper cell devitalization during cryoablation is
related to
 A. speed of freezing
 B. freezing/ thaw cycles
 C. Slow thawing is of pivotal importance
 D. all the anwers
D

46.  Q4. the optimal modality for follow up after focal therapy
 A. US
 B. PET- CT
 C. Biopsy
 D. mp-MRI with fusion technology
D

47.  Q5. Estimation of tumor volume by MRI is
 A. perfectly correlated with histology
 B. frequently under-estimated
 C. frequently ovre-estimated
 D. ideally realized by the combination of T2 & fusion
imaging.
D

48.  Q6. during the slow thaw phase:
 A. ice microcrystals recrystalize into macrocrystals with
increase in membrane damage
 B. ice melting has no role in devitalization effect
 C. All answers are wrong
 D. the temperature at the center of the ice ball is superior
to the temperature at the edge.
A

49. THE END