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FOCALTHERAPY
&
IMAGING IN PROSTATE CANCER
DR. PRATEEK LADDHA
SENIOR RESIDENT
DEPARTMENT OF UROLOGY
CMC LUDHIANA
Introduction
■ In an era of increasing prostate cancer incidence and stage
migration toward earlier disease, appropriate m...
■ A review suggests that 49% of men undergoing RP have pathological
features in the RP specimen consistent with an insigni...
RATIONALE FOR FOCALTHERAPY FOR
PROSTATE CANCER
INCREASED NUMBER OF CASES BEING
DIAGNOSEDWITH LOCALIZED, LOW
RISK , LOW GRA...
Biopsy Strategies to Detect Small
Prostate Cancers
■ Two competing reasons have contributed to the need for the
accurate d...
– High risk features may harbor high grade, and
therefore high risk, disease. Patients with findings of
■ low free PSA (0....
■ The new prostate-imaging technology that fuses MRI with
real-time, three-dimensional ultrasound appears to offer a
more ...
Targeted biopsy
■ Targeted biopsy refers to direct tissue sampling of suspicious
areas, as opposed to the older method of ...
MR US FUSION GUIDED
BIOPSY
■ Benefit in patient with active surveillance
– Confirm low volume low grade disease
– Follow l...
3DMB
■ Procedure andTechnique
■ With the patient in the dorsal lithotomy position, a transrectal ultrasound probe
mounted ...
ADVANTAGES
3DMB is a safe and effective method to
grade, stage, and locate tumor.
The self embedding procedure of
biopsy c...
Contrast-Enhanced
Ultrasonography
ADVATAGES
■ portability
■ lack of nephrotoxic
contrast agents
■ multi-repeatable
techniq...
FOR PROSTATE CANCER
■ TRUS is the classical ultrasound technique for prostate imaging, and
enables a detailed visualizatio...
COMPUTERISED USG
SOFTWARES
■ Automated Urologic
Diagnostic EXpert system
(AUDEX)
■ computerized transrectal
ultrasound (C-...
Doppler
■ PCa induces neovascularization, which results in a disturbed perfusion of
malignant tissue compared to normal pr...
CEUS
■ contrast agent is a solution of
gas- filled microbubbles with a
diameter in the order of
micrometers, smaller than ...
Prostate elastography
GENERAL DEFINITIONS
■ Focal therapy (FT)
– An anatomy-based (zonal) treatment strategy (e.g. targeting a quadrant, a lobe ...
FocalTherapy
■ Many prostate tumors are detected at a very
early stage when they are small and are
confined to one region ...
■ Focal therapy is a general term for a variety of
noninvasive techniques for destroying small tumors
inside the prostate ...
■ Because focal therapy causes minimal injury to the prostate
gland, it does not preclude further treatment with radical
p...
■ When considering targeted focal ablation, the main
focus at diagnosis is to determine:
– (1) the three-dimensional cance...
Types of FocalTherapy
■ Thermal focal therapies, use either heat or cold to destroy
tumors, include:
– Focal Cryoablation
...
Thermal FocalTherapies
FOCAL CRYOABLATION
A needle-thin probe delivers a
solution that surrounds the
tumor and kills it by...
Cryoablation
HIFU
NONTHERMAL FOCAL
THERAPIES
IRREVERSIBLE
ELECTROPORATION
(IRE)
This nonthermal ablation
technique uses a device called
the ...
IRE
PDT
MRI Guided Focal Laser
Ablation of Prostate Cancer
■ The prostate is anesthetized with local anesthesia just as is
done pr...
■ MRI is highly temperature sensitive. Therefore, the temperature of the
critical structures adjacent to the prostate incl...
Summary
Figure 3
Urology Practice 2014 1, 156-164DOI: (10.1016/j.urpr.2014.05.003)
Copyright © 2014 American Urological Associatio...
Conclusions Phase I and II studies of targeted focal therapy for
prostate cancer have demonstrated safety and efficacy.Wit...
■ Thank you
Focussed therapy and imaging in prostate cancer
Focussed therapy and imaging in prostate cancer
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Focussed therapy and imaging in prostate cancer

  1. 1. FOCALTHERAPY & IMAGING IN PROSTATE CANCER DR. PRATEEK LADDHA SENIOR RESIDENT DEPARTMENT OF UROLOGY CMC LUDHIANA
  2. 2. Introduction ■ In an era of increasing prostate cancer incidence and stage migration toward earlier disease, appropriate management of the disease requires assessment of the risk of clinical significance of the disease. ■ Minimally invasive therapies are increasingly being investigated as an alternative. ■ Prostate cancer is relatively slow growing, with doubling times for local tumors estimated at 2-4 years. ■ Some prostate cancers prove to be so small, low-grade, and noninvasive that they appear to pose little risk to the patient, and are considered indolent.
  3. 3. ■ A review suggests that 49% of men undergoing RP have pathological features in the RP specimen consistent with an insignificant or indolent cancer (organ-confined cancer < 0.5 mL, no Gleason Grade 4 or 5 component). Steyerberg EW, Roobol MJ, Kattan MW, van der Kwast TH, de Koning HJ, Schroder FH. Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram. J Urol 2007;177:107e112
  4. 4. RATIONALE FOR FOCALTHERAPY FOR PROSTATE CANCER INCREASED NUMBER OF CASES BEING DIAGNOSEDWITH LOCALIZED, LOW RISK , LOW GRADE PROSTATE CANCER PSA Screening Increasing life expectancy RADICAL PROSTATECTOMY (RP) OR RADIATIONTHERAPY (RT)
  5. 5. Biopsy Strategies to Detect Small Prostate Cancers ■ Two competing reasons have contributed to the need for the accurate diagnosis of small prostate tumors. – most patients with indolent cancers are better served by expectant management. Epstein and colleagues demonstrated that tumors with a volume 3 had an indolent course with a positive predictive value of 95%. Based on this observation, a number of groups have published their experience with active surveillance with selective delayed intervention for prostate cancer ■ PSA doubling time >4 years, ■ PSA density 50% cancer involvement, and ■ Gleason pattern >3. Using these stricter criteria, there were no prostate cancer-related deaths at 10 years,
  6. 6. – High risk features may harbor high grade, and therefore high risk, disease. Patients with findings of ■ low free PSA (0.75 ng/ml/year, ■ high grade PIN, and ■ atypia with a prior negative biopsy may in fact harbor a small focus of high grade disease (Gleason score >7), and this has been found to be as high as 14%
  7. 7. ■ The new prostate-imaging technology that fuses MRI with real-time, three-dimensional ultrasound appears to offer a more exacting method to obtain biopsy specimens from suspicious areas within the organ. ■ The new technology may be most beneficial for patients who fall into one of two categories: – those who had prior negative biopsies but have persistently elevated prostate-specific antigen (PSA) levels – "active surveillance" patients — those with low-risk prostate cancers who are being carefully monitored over time to see if their cancer progresses or becomes more aggressive. ■ Researchers found that targeted biopsy was about five times more likely to find cancer than non-targeted, systematic biopsy.
  8. 8. Targeted biopsy ■ Targeted biopsy refers to direct tissue sampling of suspicious areas, as opposed to the older method of random, systematic sampling in use since the 1980s. ■ The new method employs sophisticated MRI (magnetic resonance imaging) technology, to visualize prostate cancer, and fusion of the MR images with realtime ultrasound. ■ The result is a 20-minute procedure, done in the clinic under local anesthesia, much more accurate than the older method of prostate biopsy because of biopsy targeting.
  9. 9. MR US FUSION GUIDED BIOPSY ■ Benefit in patient with active surveillance – Confirm low volume low grade disease – Follow lesions of over time ■ Improved risk stratification for prostate cancer using MR imaging ■ FocalTherapy – Allows targeting ,treatment and follow up of only the cancer and leaves the normal prostate and nerves untouched.
  10. 10. 3DMB ■ Procedure andTechnique ■ With the patient in the dorsal lithotomy position, a transrectal ultrasound probe mounted on a stepper is attached to a standard 5-mm brachytherapy template grid secured against the perineum. ■ A Foley catheter may be placed in the urethra to aid in identifying the urethra and assess for hematuria before completing the procedure. Biopsies are obtained at 5 mm intervals from the apex to the base, laterally to medially, and anterior to posterior until the entire gland has been sampled using a standard 18-guage automated biopsy gun. Midline biopsies are obtained posterior to the urethra to avoid urethral injury.
  11. 11. ADVANTAGES 3DMB is a safe and effective method to grade, stage, and locate tumor. The self embedding procedure of biopsy cores can help to gain a maximum of information on cancer localization within the prostate. better match tumor burden with appropriate treatment selection, thereby minimizing treatment-related morbidity and potentially improving clinical outcomes DISADVANTAGES 3DMB is more time and resource intensive than standard office based TRUS biopsies. Operating room, anesthesia, duration of procedure, and number of samples obtained all add to its expense. One tertiary care institution reported that average cost of performing the procedure in an outpatient surgery setting was $5,000 to $6,000 dollars
  12. 12. Contrast-Enhanced Ultrasonography ADVATAGES ■ portability ■ lack of nephrotoxic contrast agents ■ multi-repeatable technique. ■ low costs compared with other imaging modalities DISADVANTAGES ■ user dependency ■ long learning curve. ■ 3D imaging is available, mostly ultrasound is still performed in 2D. ■ growing obesity in the society, also the limited tissue penetration poses a
  13. 13. FOR PROSTATE CANCER ■ TRUS is the classical ultrasound technique for prostate imaging, and enables a detailed visualization of the prostate. However, ■ PCa is hard to detect with standard grayscaleTRUS. ■ The classical signs for malignancy are hypoechoic lesions, vesicular asymmetry, and capsular irregularity; however, only 11–35% of the malignancies are visible on grayscaleTRUS ■ hypoechoic lesions seen, only in 17–57% of the cases malignancy is present ■ TRUS is mainly used for volume measurement and guidance of systematic biopsies. ■ In conclusion, in the diagnosis of PCa, transrectal grayscale ultrasound is lacking accuracy; therefore, an urgent improvement of TRUS is needed.
  14. 14. COMPUTERISED USG SOFTWARES ■ Automated Urologic Diagnostic EXpert system (AUDEX) ■ computerized transrectal ultrasound (C-TRUS) ■ use algorithms based on refl ected raw and visual ultrasound data, and ■ compute locations where probability of PCa is high. ■ They show higher PCa detection results in comparison with regular grayscaleTRUS. ■ However, the results are not suf ficient to rule out systematic biopsies
  15. 15. Doppler ■ PCa induces neovascularization, which results in a disturbed perfusion of malignant tissue compared to normal prostate tissue ■ Sen et al. compared color Doppler with grayscale US in targeted biopsies in 40 patients. ■ Respectively, they show a difference in sensitivity of 88.2 vs. 73.5% and specificity of 66.6 vs. 33.3%. ■ Power Doppler ultrasonography (PDU) increases the sensitivity for detection of blood fl ow compared to color Doppler. ■ A comparison between PDU imaging and systematic biopsies has been performed by Sakayra et al. andTakahashi et al. ■ A sensitivity between 77 and 90% was seen, with a specificity of 75–88% introduction of contrast-enhanced ultrasound (CEUS), improved low blood flow imaging is possible and microvascular changes Can be visualized
  16. 16. CEUS ■ contrast agent is a solution of gas- filled microbubbles with a diameter in the order of micrometers, smaller than red blood cells, and stabilized with a biocompatible shell. ■ Compatible with: – Cryoablation – HIFU In 2005, a comparison between contrastenhanced harmonic imaging targeted biopsies and systematic biopsies was performed by Halpern et al. Biopsies were performed in 301 patients. CEUS-targeted biopsies were two times more likely to fi nd cancer compared to systematic biopsies in patients with PCa. However, targeted biopsies missed 20% of cancers, which were detected by systematic biopsies alone. They concluded that although the detection rate of carcinoma is higher with CEUS-guided biopsies, systematic biopsies are still needed
  17. 17. Prostate elastography
  18. 18. GENERAL DEFINITIONS ■ Focal therapy (FT) – An anatomy-based (zonal) treatment strategy (e.g. targeting a quadrant, a lobe or both lobes sub-totally) ■ Targeted FT – A lesion-based focal treatment strategy targeting the identified tumors plus a safety margin The aim of (targeted) FT for PCa Eradication of all significant cancer(s) Subtotal ablation Any ablation where less than the whole gland is treated ■ Extended - hemiablation – An ablation where one lobe is completely treated plus a margin of the other lobe regardless of shape Index lesion The single dominant lesion in terms of grade and size where grade is more important. There can be only 1 index lesion. The term index lesion itself may be of limited use in the context of FT. It is more important to have an overview of all significant lesions that warrant treatment rather than a single defined index lesion ■ Salvage – FT Salvage FT refers to the situation where FT is applied to the prostate after whole- gland therapy, or in the same region of the prostate as previous FT. The prostate gland has to be in place
  19. 19. FocalTherapy ■ Many prostate tumors are detected at a very early stage when they are small and are confined to one region of the prostate gland. ■ These tumors cannot be felt in a digital rectal exam. They may be slow growing and pose little immediate risk to a patient's life. ■ However, because it can be difficult to predict which tumors will become life threatening, patient or surgeon may want to eliminate a clinically localized early-stage tumor rather than pursue active surveillance.
  20. 20. ■ Focal therapy is a general term for a variety of noninvasive techniques for destroying small tumors inside the prostate — leaving the gland intact and sparing most of its normal tissue. ■ In appropriate situations, focal therapy can offer several advantages for men with early prostate cancer: – Focal therapy can effectively destroy specific areas of cancer within the prostate while preserving normal prostate tissue and function. ■ Side effects of focal therapy — including changes in urinary and sexual function — are often temporary and may be less severe than those associated with more-aggressive treatments.
  21. 21. ■ Because focal therapy causes minimal injury to the prostate gland, it does not preclude further treatment with radical prostatectomy, radiation therapy, or additional focal treatment to another part of the gland, if necessary. Cancer that returns after radiation therapy may be treated with focal therapy. ■ Focal therapy is often performed on an outpatient basis or with a single overnight hospital stay.
  22. 22. ■ When considering targeted focal ablation, the main focus at diagnosis is to determine: – (1) the three-dimensional cancer location within the gland, – (2) cancer volume, and – (3) biologic potential (e.g., which aggressive foci require immediate therapy, while other indolent foci may be able to be followed or treated with a chemopreventive agent). ■ The challenge is how to define the clinically significant PCa focus based upon its natural biologic history tempered with patient life expectancy. Further research will be required to understand the biologic potential of each of the individual PCa foci within a cancerous gland
  23. 23. Types of FocalTherapy ■ Thermal focal therapies, use either heat or cold to destroy tumors, include: – Focal Cryoablation – High-Intensity FocusedUltrasound (HIFU)
  24. 24. Thermal FocalTherapies FOCAL CRYOABLATION A needle-thin probe delivers a solution that surrounds the tumor and kills it by freezing it to a very low temperature. Because focal cryoablation targets only a small area within the prostate, it also has fewer side effects than other cryoablation techniques, which freeze the entire prostate gland. HIFU Uses the energy of sound waves, directed to the tumor with the help of MRI scans, to superheat and eliminate small tumors. HIFU is an attractive focal therapy approach because it is relatively noninvasive. The effectiveness of this treatment is monitored in real time, using MRI to measure the temperature within the prostate during therapy.
  25. 25. Cryoablation
  26. 26. HIFU
  27. 27. NONTHERMAL FOCAL THERAPIES IRREVERSIBLE ELECTROPORATION (IRE) This nonthermal ablation technique uses a device called the NanoKnife® to pass an electrical current through the tumor. The electricity creates very tiny openings (called pores) in tumor cells, leading to cell death. Ultrasound or CT is used to focus the current precisely on the tumor, sparing blood vessels and other tissues. VASCULARTARGETED PHOTODYNAMIC THERAPY (VTP) A drug that destroys tumor cells and the blood vessels that support them is given intravenously and moves to the inside of the tumor. The drug is activated by exposing it to light of a very specific color (wavelength), which is delivered to the tumor site with specially designed fibers placed within the prostate. The photoactive substance can then directly target the vessel supplying tumor, closing it off and leading to the destruction of the tumor.
  28. 28. IRE
  29. 29. PDT
  30. 30. MRI Guided Focal Laser Ablation of Prostate Cancer ■ The prostate is anesthetized with local anesthesia just as is done prior to a prostate biopsy. ■ The technique is performed under local anesthesia in the MRI machine. ■ The region of interest harboring the prostate cancer is identified and a laser fiber is introduced directly into the prostate cancer under MRI guidance.
  31. 31. ■ MRI is highly temperature sensitive. Therefore, the temperature of the critical structures adjacent to the prostate including the rectum, urinary sphincter, and erectile nerves are monitored in real time so it is extremely rare to have any collateral damage to these structures. ■ The temperature of the ablation site within the region of interest known to harbor prostate cancer is also monitored in real time to optimize destruction of the indexed lesion of the cancer. ■ At the completion of the procedure, contrast is administered to show that the region of interest has been successfully ablated.
  32. 32. Summary
  33. 33. Figure 3 Urology Practice 2014 1, 156-164DOI: (10.1016/j.urpr.2014.05.003) Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions
  34. 34. Conclusions Phase I and II studies of targeted focal therapy for prostate cancer have demonstrated safety and efficacy.With improved imaging, new MRI-TRUS fusion targeted biopsies and standardized patient selection criteria, phase III study is under way, perhaps setting the stage for a new era of prostate cancer therapy for many individuals. Moving Forward the State of the Art in Prostate Cancer Treatment: Targeted Focal Therapy Crawford, E. David et al. Urology Practice , Volume 1 , Issue 3 , 156 - 164
  35. 35. ■ Thank you
  • DrVarunKatiyarnewdelhi

    Mar. 12, 2019

Focussed therapy and imaging in prostate cancer

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