2-D Standard Sonogram Versus 3-D Doppler
The regular 2-D sonogram may miss low-grade cancers that have the same appearance as the normal gland, which account for up to 40% of prostate tumors according to Dr. D. Downey, in the 1997 journal Urology. The overall accuracy is about 50%. The accuracy is better in glands that have never been subjected to a biopsy or treated in any way. The accuracy is lower in prostates that have been biopsied multiple times or in persons who have been treated with radiation or hormones.
Power Doppler
The power Doppler study adds about 30% more accuracy, since the abnormal blood vessels provide a road map to the tumor, however, detours on the road may occur with older 3-D systems in the presence of stones or calculi. Indeed, a US patent, number 5,860,929, was obtained by Norwegian scientists to determine power Doppler blood flows in optimally diagnosing PCa's. When a stone is identifiable, the sound waves bounce back so strongly that they create a false color pattern. This pattern to the trained clinician will not be mistaken for a tumor vessel.
Uniquely 3-D Power Doppler Formats
Fortunately, the Doppler technology has other formats that correctly identify artifactual or spurious colors, distinguishing it from a true cancer. In Dr. Bard’s practice combining 3-D PDS with focused computer-aided vascular MRI exams, we have achieved a 97% overall accuracy in diagnosing and staging PCa's. An important exception occurs in the seminal vesicles, which sit on top of the prostate gland generating the fluid that produces the ejaculation. Early cancer spread to these paired vesicles may be missed by the 3-D PDS. When a tumor is found near or adjacent to the seminal vesicles at the base of the prostate, MRI scans are mandatory. Another important advantage of 3-D PDS is the ability to accurately measure tumor volume and density.
3-D Power Doppler Sonography and Tumor Volume
A meaningful use of 3-D technology is the determination of tumor volumes. Clinically “insignificant PCa” is generally defined as:
•A volume less than 0.5 cc, which means the cancer is less than 7x8 mm.
•A Gleason score of less than or equal to 7.
•No extra-capsular extension, implying: no tumor beyond the prostate capsule; no invasion of seminal vesicles; no boney metastases; and no lymphadenopathy1
3-D Power Doppler Sonography and Tumor Density
Tumor density is an important factor in determining both the grade of the tumor and response to treatment. As explained elsewhere, some tumors may remain the same size or actually increase in volume while responding to treatment. Density, accurately measured by recent software advances in 3-D PDS is a principal indicator of both grading (especially aggressiveness) and response to treatment on a real-time basis. (The system with this capability is FDA approved.)
The Future Potential for MRI and 3-D Doppler Ultrasound
When you look around the world at advances and innovation in MRI and 3-D Doppler technology, software, and utilization, it is evident that this technology will become an important part of cancer practice, especially in this age of cost containment. Some of these techniques are not new, and are in practice outside the US. Below are just two very promising examples.
3-D Doppler
In 1999 at the University of California San Diego campus, a French medical student, Dr. Olivier Lucidarme developed a highly sensitive technique to improve Doppler ultrasound. Special bubbles injected intravenously greatly improved imaging of small vessels. To date, our FDA has not approved this technology and Dr. Lucidarme now practices this methodology in Paris at the Pitie-Salpetriere Hopital, the largest teaching center in Europe. Italian researchers at the University of Rome, Drs. Vito Cantisani and Francesco Drudi, have shown this technology to show cancers unsuspected by other means.
MRI
Advanced MRI scans performed in Europe are not available in the US, nor are certain sophisticated radioactive bone scans, or techniques for evaluating lymph node involvement, allowed in the States at this writing. For example, in 2004, Dr. Jelle Barentsz described a new technique to evaluate cancer spreading to the lymph nodes at the International Congress of Radiology. This uses MRI with ferumoxtran-10, a novel contrast agent called Combidex in the United States. The lymph node technique is termed MRL (magnetic resonance lymphangiography) and ferumaxtran-10 is being used in a wide range of MRI procedures throughout Europe, as it has shown a very good safety record, especially as it does not induce nephrogenic systemic fibrosis (NSF), a recently recognized severe complication associated with gadolinium (Gd)-based contrast agents (GBCAs) when used with patients who have compromised kidney function. GBCAs are used as standard in the United States.
This technology is extremely important since MRI is the best way to image abnormal glands that are hidden or inaccessible at surgery. The imaging shows the size and location of the lymph nodes as well as the presence of cancerous tissue as small as 1/5 inch. This critical piece of information that pinpoints cancer infiltration tells where the spread occurs and allows for accurate treatment planning. The current “gold standard” for lymph node evaluation is surgery called pelvic lymph node dissection. Clearly, this invasive exploratory operation, where the surgeon searches with his hand for hard lumps in the abdomen, cannot find all the tiny sites to which cancer spreads. Moreover, the metastases to nodes are generally subcentimeter and so are likely to be missed clinically and radiographically. In addition, the most reliable sign of metastatic adenopathy is in the perirectal space, which is not routinely examined at surgical dissection. The MRL exam is so accurate that a negative exam translates into a 96% chance that there is no metastatic disease to the lymph nodes. In addition to sparing patients from the risk and pain of surgery, this methodology reduces health care costs.
PROACTIVE MONITORING
The monitoring approach presented here is based on Dr. Bard’s 39-years experience in the field of diagnostic ultrasound, 15-years of imaging the prostate with power Doppler blood flows, and 6-years of performing 3-D PDS and comparing the results with high resolution MRI scans of the pelvis with special sequences formulated specifically for the prostate. Dr. Bard has diagnosed, observed, and shared in the treatment of some 5,900 patients. Through nutritional support, medical treatment when appropriate, and 3-D monitoring on a schedule dictated by each individual’s current situation, only 5 of these 5,900 men have died from their PCa in a 10-year time period. (This compares very favorably to the expected 239 deaths from PCa within 4 years of diagnosis, based on figures from the Health Professionals Follow-Up Study for men diagnosed with nonmetastatic PCa observed from 1990 to 2008.6)
ProActive Monitoring couples 3-D Doppler and MRI imaging at regular intervals with the B-Sit/AOX) nutritional support. The B-Sit/AOX approach was first developed out of Arthur Bartunek’s early work with coenzyme Q10 (CoQ10) and cofactors that improved Q10 outcomes, especially for cancers. The formulations and protocols used during proactive monitoring were further refined with feedback from the progressive 3-D Doppler monitoring of men with varying stages of PCa. During the 10-years of this process, improvements in imaging have allowed changes to be tracked more accurately, and to make appropriate nutritional adjustments based on this. In addition, the use of several nutritional items, notably curcumin and tocotrienols, have been independently developed for use with cancer and are reaching phase II and phase III clinical trials. These have been included in the protocol and are discussed here.