Mark Scholz, MD – Treating and Preventing Bone Metastasis Dr. Scholz is a medical oncologist with a practice in the LA area that specializes in prostate cancer. He worked with Dr. Stephen Strum at the PCRI for several years and is well experienced in issues relating to PCa. He first differentiated PCa from other cancers by identifying its unique attributes. Among these is the generally slower growth rate for PCa cells. Also, its relative ease of monitoring with PSA tests. He indicated that the growth factors present in bone assist PCa to flourish. Because it is uniquely sensitive to testosterone, conventional anti-hormonal therapies do cause bone weakening. So an inherent contradiction in medical therapy for PCa is that the most effective treatment, significant testosterone reduction, is also the most damaging to bone health. Dr. Scholz made the point that “prostate cancer uniquely spreads only to bone while sparing other sensitive organs such as lung, brain, and liver”. ( ED. NOTE: We know of several cases where metastatic PC lesions have gone to the liver and even involved bladder tissue). Because of its high affinity for metastasizing to bone, treatments that can slow that progression or inhibit PCa colonization to the bone, will materially improve overall survival. Bone pane from metastatic prostate cancer is potentially crippling and can turn PCa patients into bed ridden victims. He reviewed the methods for detecting bone mets including MRI, Bone Scans, conventional X-rays, and PET scans. Prostascint scans are also used and now, with fusion imaging procedures, combination of scans in tight registration have become highly useful in clearly identifying exact locations and extent of metastatic tumors. Scholz also discussed the use of Fosamax and Aredia (types of bisphosphonates) in treating PCa that is metastasizing. He referred to the literature that shows an overall slowing in the rate of metastatic disease to bones when these materials are used. Zometa is the most recent development in this field. ATRASENTIN is another material being explored for inhibition of metastasis. Currently, Zometa is the drug of choice for dealing with PCa that is metastasizing. Treatment of pain from lesions on bone can be treated with spot radiation using external beam equipment, or with radioactive compounds that are structured to identify and adhere to bone lesions where the radiation delivered can ease the pain. He discussed the uses of radioactive Strontium and Samarium for this purpose. He showed data in which Zometa was studied vs a placebo to measure so-called SREs (skeletal related events) after time. With placebo, some 44 SREs occurred in approx 15 months, whereas the Zometa data showed only 33 SREs after the same period. That is a reduction of 11/44 = 25%. He further reviewed the idea that preventing bone metastasis may be “easier” than treating mets already in place. The overall objective in preventing bone lesions from developing would be to “make the soil of the marrow inhospitable”. He quoted from Paget (discoverer of Paget’s disease) as follows: “When a plant goes to seed, its seeds are carried in all directions; but they can grow only if they fall on congenial soil.” That was written in 1889 by Paget. Dr. Scholtz illustrated his lecture with a slide that showed how normal bone is in a constant process of bone resorption and bone formation. And when that cycle is disrupted by the introduction of PCa metastatic colonies, bone degradation pre-dominates. Osteoporosis provides fertile soil for mets to root in. Therefore maintaining a healthy skeletal structure is a highly desireable objective for all men and women. Females who have to endure reduced estrogen also can be ravaged by osteoporosis. This is a common danger in breast cancer patients. The loss of calcium, he pointed out, doesn’t make bones become smaller rather they become thinner and more porous. Men dealing with PCa should keep watch on their bone density over time. He suggested that the best method for monitoring bone density is with QCT (quantitative CT scans) as compared to the more common DEXA scan. Also monitoring of Pyrilinks-D can identify bone degradation while it is occurring. Low calcium levels in blood encourage the leaching of calcium from the bones themselves leading to osteoporosis and bone breakdown. Therefore maintaining normal levels of calcium in the blood is essential for not only bone health but also muscular, mental and coronary functions. He recommended 500 mg doses of calcium citrate with dinner and at bedtime as well as the trace minerals of magnesium, boron, and fluoride containing elements. Dr. Scholz suggested avoiding bone meal and oyster shell sources because they may contain excessive levels of lead. An interesting, if not challenging, suggestion was offered by Scholz. He recommended Vitamin D (Rocaltrol) as Zometa for preventing osteoporosis. The standard dose he referred to was only 0.5 mcg/day (mcg = micrograms). This conclusion was referenced in a 2004 publication by Shane (NEJM Feb. 04). Dr. Scholz also identified other causes of bone breakdown: “excess alcohol, tobacco and caffeine. High sugar diet, poor physical fitness, increased thyroid or parathyroid activity, excess vitamin A, and elevated homocysteine. “ ED. NOTE: Excess homocysteine is also believed to be responsible for increases in heart artery disease. He concluded his lecture by referring again to Zometa as “the only agent that builds bone while on TIP (Testosterone Inhibiting Pharmaceuticals)” He said Zometa “appears safe” on a quarterly administration schedule and it has “proven anti-cancer efficacy against advanced metastatic disease”. The development of a new bio-engineered drug called Osteoprotegrin by Amgen is underway. This is to function as a supplement or “booster” to the body’s own production of this anti-osteoclastic material. How far from market availability was not made clear. To maintain good bone health one should monitor bone density annually and establish a base line level of Pyrilinks-D quarterly. Calcium citrate as mentioned above along with Calcitriol (Vitamin D) should be routinely consumed. If metastasis is potentially there, then taking 4 mg/quarterly Zometa was recommended. Dr. Scholz listed five criteria in defining who is at risk for bone mets: 1. Men who relapse after RT or RP or cryosurgery 2. Men with Gleason scores 7 or > 3. PSA >15 and PAP >normal 4. Known lymph node involvement or seminal vesicles 5. PSA doubling time < 12 months. NPC Program Review, 6/05 Remember we are NOT Doctors and have NO medical training. 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