According to the BJU, 1999, "during the past decade, prostate cancer has moved centre-stage having for many years been the 'Cinderella' subject of cancer research. Four principal factors have been responsible for this shift in emphasis. First, a realization of the magnitude of prostate cancer on a world scale. This disease now has the highest incidence of any noncutaneous malignancy in the Western world, and is the second highest cause of cancer death in males, after lung cancer. Second, the controversial roles of PSA as a primary screening modality together with development of radical prostatectomy as a definitive procedure in the management of clinically early prostate cancer. Third, the prevalence of BPH and the morbidity associated with this disease has stimulated a range of investigations, which have resulted in enhanced understanding of the developmental biology of the prostate gland, particularly the importance of stromal-epithelial interaction. Fourth, distribution of the Dunning rat prostate carcinoma model, together with more recently developed cell systems, now provides a comprehensive range of clonally derived, genotypically stable, and behaviorally distinct, prostatic epithelial cell variants. Comparative analysis of phenotypically distinct cell lines within these systems has provided a unique opportunity to identify individual factors, which determine particular aspects of prostatic cancer-cell behavior. These four factors, together with recent advances in cellular and molecular biological techniques, are now revealing fundamental processes underlying the aetiopathogenesis of prostatic epithelial neoplasia. Consequently, studies into prostate cancer are currently leading many advances in basic cancer research."

"Recognition of cellular features which accurately predict the behavior of prostate cancer occurring within a specific patient is a major challenge facing contemporary urological pathology. Traditionally, diagnostic histopathologists have attempted to forecast such behavior by comparing the morphological features of a malignancy with those of its normal tissue counterpart. Although this approach has identified some features common to prostate cancers as a group, it has been singularly inadequate at predicting the behavior of individual cancers at the time of their original diagnosis. Paradoxically, primary prostatic carcinomas which are morphologically indistinguishable according to currently available criteria, and discovered incidentally, are not equally lethal but exhibit an extensive range of behavioral phenotypes for which reliable diagnostic markers are not yet available. Thus, a fundamental dilemma in the current management of prostatic cancer is that it is not yet possible to identify clinically important cancers while they are confined to the prostate gland, and particularly not before either local invasion or metastatic spread has occurred. Conversely, clinically unimportant cancers (i.e. those which are anatomically localized and have not yet developed a potentially metastatic phenotype) do not require aggressive treatment, from which patients should be spared to lessen overall morbidity. Unfortunately, anatomically localized prostatic neoplasms are frequently not benign. For many patients with potentially metastatic disease, although progression might be slow, it will remain inexorable until such a time that biologically appropriate therapeutic approaches are developed to curb the otherwise inevitable malignant behavior."

There is no proven link between frequency of sexual activity and prostate cancer risk.

To be considered for this treatment, the patient must have positive bone scans and experiencing pain.

Instructor's Comments:
Q: How does pain become a relevant vital sign in palliation of bone cancer symptoms?
A: Before the patient can be considered for Quadramet Samarium-153, he/she must be diagnosed with pain. Pain management in the terminally ill has become very important in the medical field. The advantage of Quadramet or metasteron is, unlike narcotic analgesics, it is one injection and does not make the patient a zombie. The patient is aware of their surroundings and responsive to interaction with other people. The terminally ill cancer patients like to spend meaningful time with relatives and children and narcotic analgesics do not allow this where as Sr-89 or Sm-153 does.

Samarium-153 provides targeted activity at the site of pain. It causes minimal exposure to normal tissue (average beta particle penetration is 1.7 mm in bone and 3.1 mm in soft tissue.) Pain relief is typically observed as soon as one week after administration and persisted for a median of 16 weeks in nearly half of the patients. In clinical trials, white blood cells (WBCs) and platelet counts decreased consistently to nadirs of 40% to 50% of baseline within 3 to 5 weeks. WBC and platelet counts tended to return to pretreatment levels within 8 weeks.

Radiopharmaceutical Considerations

Instructor's Comments:
Q: What special radiopharmaceutical handling is required of this high energy Beta emitter?
A: The specific gamma-ray constant for samarium-153 is 0.46 R/mCi-hr at 1 cm (1.24x10-5 mSv/MBq- hr at 1 Meter). The half-value thickness of lead (Pb) for samarium-153 is approximately 0.10 mm. The use of 1 mm of lead will decrease the external radiation exposure by a factor of approximately 1,000. Quadramet should be stored in a lead-shielded container and frozen until use.

Q: Because prostate cancer patients may be predisposed to incontinence, how are post administration contamination issues addressed?
A: Patients who are incontinent need indwelling urinary catheter for 3 days.

Patient Preparation

Drink at least two cups (one pint) of water, juice, or other liquid just before receiving Quadramet Samarium-153. This will fill the bladder and help to protect it from exposure to the radiation. The patient is not required to do bowel prep. The technologist should be aware if the patient has had an allergic reaction to a bone scan drug or any other phosphonate drug. The patient dons not need to discontinue other medications that they may currently be taking.

Findings

After reviewing bone scan on 8/28/03 again demonstrating multiple metastatic lesions as well as recent lab results (platelet value of 216 and creatinine of 0.9 on 8/28/03), the risks and benefits of the Samarium therapy was again reviewed with the patient and his daughter. The precautions for this therapy were also reviewed. If a patient is pregnant or nursing, they should not use Samarium. It is recommended that the patient refrain from intimate sexual contact for about 12 hours. Written informed consent was obtained at this time, and placed in the patient’s chart. Patient was given 98.7 mCi of Quadramet Samarium-153 therapy by slow intravenous drip. Patient tolerated this procedure well, and had no complaints at any time. The patient was evaluated after infusion, and was determined to have a radiation of 3.5 mRad per hour at 1-meter distance. The patient is to have his complete blood cell count including platelets drawn every Friday for the next 8 weeks, and orders for this test were given to the patient. The patient was encouraged to drink as much fluid as possible over the next few days which will fill the bladder and help to protect it from exposure to the radiation.

Sodee,B., Early. Principles and Practice of Nuclear Medicine, by: D. Bruce Sodee

Foster, C.; et.al. The cellular and molecular basis of prostate cancer. BJU International (January 1999), 83.2