Focal therapy for localized prostate cancer: a future possibility?
Posted Sep 17 2008 1:52pm
For many years now, some physicians and researchers have been seeking ways to implement “focal therapy” for certain categories of localized prostate cancer. Focal therapy for prostate cancer is effectively the same idea as was “lumpectomy” for localized breast cancer — the idea that it might be possible to treat the localized disease effectively by elimination of the specific focus of cancer in the prostate without the need to treat or remove the entire prostate gland.
It is certainly the case that some newer methodologies have brought the possibility of focal therapy for localized prostate cancer closer to reality. However, it is also the case that, just as there are potential “pros” to the idea of focal therapy, there are also some very real “cons.”
To review the current state of prostatecancer detection and treatment
To review era specific trends in pathological characteristics of localizedprostatecancer
To examine the rationale for and concerns regarding focaltherapy and
To r eview methods of delivering focaltherapy
In addition, the task force decided to propose study design parameters for the prospective evaluation of focal therapies.
The complete article is relatively short, and The “New” Prostate Cancer InfoLink does not intend to offer a detailed summary. The following are a series of key points made by the authors:
At present we are still not able to clearly distinguish between patients at low risk and higher risk for progressive prostate cancer because of problems with appropriate identification of cancerous tissue within the prostate — by imaging studies, biopsy studies, and biopsy pathology.
At least in the USA and Europe, large numbers of men are almost certainly receiving unnecessary treatment for low risk, localized prostate cancer that involves complete removal of the prostate gland or some other form of ablative treatment of the entire prostate gland.
Under the current circumstances, most men (and particularly younger men) who are diagnosed with prostate cancer are unwilling to consider any form of expectant mangement (watchful waiting, active surveillance) because of the possibility for progressive micrometastatic disease.
The size of the largest tumor identified in the prostates of men undergoing treatment (the “index” tumor) has significantly declined (from 5.3-6.0 cm 3 in the 1980s to 2.2-2.4 cm 3 in the past decade.
The proportion of patients treated with radical prostatectomy and subsequently shown to have unifocal tumors is between 13 and 38 percent (with variations largely dependent on patient selection and pathological sectioning technique).
A very high percentage of cancer volume (~ 80 percent) in any specific patient is contributed by the primary or index tumor.
The authors go on to state that:
Based on these studies it is apparent that many patients with multifocal disease have a relatively small volume of secondary tumors, which rarely contain higher primary Gleason grades than the index tumor and are unlikely to affect overall disease progression. Consequently a large population of patients appears to have biologically unifocal disease, that is, multifocal elements with nonindex cancers that are unlikely to affect ultimate outcomes.
A Rationale for Focal Therapy — Given the preceding scenario, the task force presents the following rationale for the development of focal therapy for prostate cancer:
Many solid tumors have traditionally been treated with radical surgery but selective, organ-sparing therapies are now common for tumors of the breast, skin and kidney, resulting in equivalent rates of cancer control, lower morbidity rates and less disfigurement.
Critical Criteria for Clinical Acceptability — The task force also suggests that any focal therapy that is to be effective in the treatment of localized prostate cancer will probably need to:
Demonstrate preclinical evidence of tumoricidal activity throughout the entire target zone
Allow real-time treatment monitoring
Access the prostate percutaneously, via the rectum or through the urethra
Affect only the dominant (”index”) tumor focus, causing minimal alteration of structures essential for sexual, urinary and bowel function
Permit the possibility for re-treatment if necessary and
Allow subsequent whole gland therapy (e.g., surgery or radiation) without excess morbidity
The Importance of Good Cancer Characterization — The task force notes the importance of high quality characterization of relatively low risk cancer as critical to the effectiveness of focal therapy. Specifically they note that:
Reliable imaging modalities will be essential to the proper identification of candidates for focaltherapy, confidence in targeting lesions for treatment, appropriate evaluation of results, and follow-up monitoring for treatment failure.
Extensive biopsy sampling can now be used to more accurately characterize prostatecancer grade and location. With 12 or more biopsy cores, the rate of Gleason upgrading at radical prostatectomy may be as low as 12 percent, and transperineal “mapping” biopsies may offer even greater accuracy.
While unifocal cancer is difficult to rule out with biopsy strategies alone, accurate identification of men highly likely to have low grade, low stage cancer has been validated with sophisticated nomograms; when used in combination with MRI, these tools can identify men with prostatecancer who have a low probability of large, aggressive cancer elsewhere in the prostate.
Focal Therapy: Concerns and Options — The task force identifies four categories of treatment that appear to offer the potential for development as forms of focal therapy:
High-intensity focused ultrasound (HIFU)
Radiation therapy (ncluding both external beam radiotherapy and brachytherapy) and
Photodynamic therapy (PDT)
However, they also note the following concerns about the development of clinical trials of focal therapy:
An important limitation of focaltherapy trials would be the inclusion of patients with large or aggressive (Gleason 4+3 or greater) cancers
The consequences of improperly designating a patient for focaltherapy may be profound; although smaller non-index cancers rarely determine prognosis, there are data to suggest that non-index tumors can metastasize.
A presumed but unproven advantage of focaltherapy is the lower likelihood and severity of treatment-related morbidity; this will need to be confirmed through collection of relevant quality of life and other outcomes data.
Recommendations for Research — The task force offered a series of recommedations for future research on focal therapy:
Candidates for enrollment in trials of focaltherapy for localizedprostatecancer should meet low risk criteria based on clinical, biopsy and imaging data.
Appropriate candidates may include both patients with a singular focus of prostate cancer and patients with a primary “index” tumor and a small number and quantity of secondary tumors of low Gleason grade
Outcome measures for focaltherapy trials should at minimum include
Extensive posttreatment biopsy mapping to determine treatment effect and identify disease persistence
Imaging to characterize treatment effects and their correlation with outcome
Urinary, bowel and sexual morbidity rates
Rates of biochemical and clinical progression and re-treatment
Patient reported quality of life criteria measured longitudinally
What Is the Real Potential for Focal Therapy?
The “New” Prostate Cancer InfoLink is of the opinion that focal therapy for localized prostate cancer is simply a matter of time.
For this type of therapy to become a reality, in our opinion, the following are critical necessities:
A major “jump” in our ability to accurately define patient risk, based on the quality of available imaging and biopsy data pre-treatment
A significant improvement in the “miniaturization” of treatment capabilities for prostate cancer (such that instead of treating at the glandular level, we are actually thinking about treatment at something closer to the cellular level)
We cannot project a specific timeline for these advances, but it wouldn’t surprise us at all if they came available in the next 10 years.