An Evaluation of Focal Therapy in the Treatment of Localized Prostate Cancer An Evaluation of Focal Therapy in th
Lead Research Organisation:
University College London
Department Name: Surgery
Abstract
The choice for men who have prostate cancer that has not spread outside the gland is between active surveillance and treating the whole gland with surgery or radiotherapy. Active surveillance involves monitoring the disease using blood tests and repeated biopsies every 2-3 years. Treatment is given only if the cancer shows signs of progressing. The benefit of whole-gland treatment in reducing the risk of dying from cancer is 5% or less within 10 years. However, treatment carries risk of incontinence, impotence and rectal problems. These occur because treating the whole gland leads to damage to structures immediately surrounding the prostate
This programme of research will see if prostate cancer management can be developed in a similar way to how breast cancer treatment changed two decades ago. Women usually had to undergo an operation to remove the whole breast whereas currently, most women undergo a lumpectomy of only the cancer. This proposal will evaluate a similar principal in prostate cancer. In other words, in men with prostate cancer can we destroy only the areas of cancer and achieve lower side-effects. At the same time, can we maintain good cancer control.
This programme of research will see if prostate cancer management can be developed in a similar way to how breast cancer treatment changed two decades ago. Women usually had to undergo an operation to remove the whole breast whereas currently, most women undergo a lumpectomy of only the cancer. This proposal will evaluate a similar principal in prostate cancer. In other words, in men with prostate cancer can we destroy only the areas of cancer and achieve lower side-effects. At the same time, can we maintain good cancer control.
Technical Summary
Background
The choice for men who have localised prostate cancer (PCa) is between active surveillance and treating the whole gland with surgery or radiotherapy. Active surveillance involves monitoring the disease 3-monthly with biopsies and blood tests. Radical therapy is instituted if the cancer progresses. The absolute risk reduction in mortality, as demonstrated in a randomised controlled trial, from radical surgery is 5% within 10 years. This difference is probably smaller in the PSA-screened population. However, radical treatment carries risk of incontinence, impotence and rectal problems. These occur because treating the whole gland causes damage to structures surrounding the prostate.
Focal Therapy Hypothesis
Fewer side-effects and effective early cancer control can be achieved by targeting areas of prostate cancer.
Aims
1. Evaluate whether localised PCa is suitable for focal therapy
2. Evaluate localisation of PCa using magnetic resonance imaging
3. Evaluate the patient acceptability of focal therapy
Objectives
1. Determine the proportion of men that may be suitable for focal therapy in the UK on histological specimens.
2. Determine the side-effects and early cancer control of focal therapy in a trial setting.
3. Investigate the role of different MRI modalities in localising PCa against prostate mapping biopsies.
4. Investigate the attributes of focal therapy that will make it acceptable for men with PCa using discrete choice analysis
Design and Methods
1. Review of histological whole-mount specimens and prostate template mapping biopsies
2. Conduct of 2 phase II trials in which malignant areas will be identified using prostate mapping biopsies and ablated using high-intensity focused ultrasound (HIFU). HIFU causes coagulative necrosis using a rectal probe to transmit sound-waves that heat up discrete areas to 80-90°C. One trial will evaluate hemiablation for unilateral PCa and the other will evaluate focal-ablation of low-volume cancer areas on both sides.
3. MRI localisation accuracy of PCa will be analysed using prostate mapping biopsies as a reference standard. Qualitative analysis and quantitative visual analysis will be used to assess accuracy of dynamic contrast enhanced and diffusion weighted MRI.
4. Discrete choice experimentation, an accepted approach for elicitation of preferences of one treatment over another, will assess the key attributes of focal therapy from a patient perspective.
Research Training
This programme will equip the applicant for an academic career in Clinical Epidemiology involving practice-oriented translational and health services research such as clinical trial methodology and health technology evaluation (therapeutic and diagnostic test evaluation) (all are MRC priority capacity development areas and priority areas in the Walport report). The MSc in Clinical Trials and attendance at discrete choice analysis workshops and UCL Skills development programme will be a formal part of this training. In addition, specific training in medical image analysis/processing and histopathological evaluation will form important basic research skill elements. Clinical training in core urology as well as sub-specialist training in ablative techniques (HIFU, cryosurgery, photodynamic therapy, radio-frequency ablation) will equip the applicant for practice as a Consultant Urologist. These elements will form a strong basis for independent post-doctoral research.
The choice for men who have localised prostate cancer (PCa) is between active surveillance and treating the whole gland with surgery or radiotherapy. Active surveillance involves monitoring the disease 3-monthly with biopsies and blood tests. Radical therapy is instituted if the cancer progresses. The absolute risk reduction in mortality, as demonstrated in a randomised controlled trial, from radical surgery is 5% within 10 years. This difference is probably smaller in the PSA-screened population. However, radical treatment carries risk of incontinence, impotence and rectal problems. These occur because treating the whole gland causes damage to structures surrounding the prostate.
Focal Therapy Hypothesis
Fewer side-effects and effective early cancer control can be achieved by targeting areas of prostate cancer.
Aims
1. Evaluate whether localised PCa is suitable for focal therapy
2. Evaluate localisation of PCa using magnetic resonance imaging
3. Evaluate the patient acceptability of focal therapy
Objectives
1. Determine the proportion of men that may be suitable for focal therapy in the UK on histological specimens.
2. Determine the side-effects and early cancer control of focal therapy in a trial setting.
3. Investigate the role of different MRI modalities in localising PCa against prostate mapping biopsies.
4. Investigate the attributes of focal therapy that will make it acceptable for men with PCa using discrete choice analysis
Design and Methods
1. Review of histological whole-mount specimens and prostate template mapping biopsies
2. Conduct of 2 phase II trials in which malignant areas will be identified using prostate mapping biopsies and ablated using high-intensity focused ultrasound (HIFU). HIFU causes coagulative necrosis using a rectal probe to transmit sound-waves that heat up discrete areas to 80-90°C. One trial will evaluate hemiablation for unilateral PCa and the other will evaluate focal-ablation of low-volume cancer areas on both sides.
3. MRI localisation accuracy of PCa will be analysed using prostate mapping biopsies as a reference standard. Qualitative analysis and quantitative visual analysis will be used to assess accuracy of dynamic contrast enhanced and diffusion weighted MRI.
4. Discrete choice experimentation, an accepted approach for elicitation of preferences of one treatment over another, will assess the key attributes of focal therapy from a patient perspective.
Research Training
This programme will equip the applicant for an academic career in Clinical Epidemiology involving practice-oriented translational and health services research such as clinical trial methodology and health technology evaluation (therapeutic and diagnostic test evaluation) (all are MRC priority capacity development areas and priority areas in the Walport report). The MSc in Clinical Trials and attendance at discrete choice analysis workshops and UCL Skills development programme will be a formal part of this training. In addition, specific training in medical image analysis/processing and histopathological evaluation will form important basic research skill elements. Clinical training in core urology as well as sub-specialist training in ablative techniques (HIFU, cryosurgery, photodynamic therapy, radio-frequency ablation) will equip the applicant for practice as a Consultant Urologist. These elements will form a strong basis for independent post-doctoral research.