BERKELEY, CA (UroToday.com) - Unlike in other areas of oncologic focus, the role of the nuclear medicine physician in a multidisciplinary team for the management of prostate cancer disease had been largely confined to imaging; this was due to the lack of efficacy of radio-metabolic therapies to impact the progression of disease, and ultimately, survival. An exception may be the opportunity to treat, with β-emitting-radiopharmaceuticals, patients presenting with bone metastases due to castration resistant prostate cancer. These radio-drugs were approved by health authorities with the goal of relieving bone metastases pain without any curative purpose. Radionuclides used as single arm, did not significantly demonstrate prolonged survival and were associated with important hematologic adverse events. Therefore the use of beta-emitting radiopharmaceuticals was mostly limited to the treatment of patients presenting with terminal disease stage.
The introduction of the alpha-emitting radiopharmaceutical radium 223 radically changed this scenario. The radio-drug is the first one demonstrating improved survival in patients with bone metastases related to castration resistant prostate cancer. The pivotal study carried out on 921 symptomatic CRPC patients showed that radium 223 induced a statistically significant survival improvement compared with placebo (median, 14.9 vs 11.3 months; hazard ratio, 0.70; 95% confidence interval, 0.58-0.83; P < .001). In addition, the good safety profile and the opportunity to avoid clonal selection of tumor cells offered the opportunity to treat the early stage of the disease. This new therapy has been recognized as having the highest levels of evidence according to the current NCCN guidelines and has thus become an important option for treatment-naive patients who progressed to docetaxel. The authors reported that treatment with radium 223 dichloride could be a reasonable alternative to treatment with docetaxel, because this agent has far less toxicity.
Although it is not the only treatment option, Radium 223 is considered the new standard of care for patients with bone metastases from CRPC. The peculiarity of the mechanism of action requires the use of Radium 223 in patients who have bone metastases before their clinical picture evolves with the appearance of visceral metastases, as they benefit from other therapies. Patient selection may be the key to the efficacy of the drug. We believe that patients with very early symptoms are viable candidates to be treated with radium 223, with the goal of limiting earlier oligometastatic bone-lesions diffusion that could be responsible for the development of late-occurring visceral metastases. Patients with numerous nodal or visceral metastases or patients with terminal stages of disease (life expectancy less than 3 months) should be excluded from alpha-emitting treatment.
The availability of a new radiopharmaceutical agent for prostate cancer could encourage cooperation between oncologists and nuclear medicine physicians. Radium 223 may represent for oncologists a sort of “magic bullet” that, at least theoretically, should be able to bypass cancer cell resistance, limiting the development of resistant clone selection in tumor tissue. The favorable efficacy and safety profile of this alpha emitting drug -- as well as its lack of induction of tumor resistance -- may allow it to leap the barriers that have limited the use of previous radiopharmaceuticals. Radium 223 is being studied alone or in combination with standard anti-tumor agents in prostate cancer as well in other bone metastases tumors. Combination studies between radium 223 and the commonly used agent docetaxel are currently ongoing to evaluate efficacy; a previous phase 1 study showed that this resulted in a well-tolerated approach. Similarly, combination studies with abiraterone and enzalutamide are in progress, representing important therapeutic strategies for patients with visceral and encephalic metastases. A third phase of the studies will concern the use of radium 223 in patients with bone metastases induced by different tumors, such as breast cancer , non-small-cell lung cancer, thyroid cancer, and multiple myeloma, as well as in primary tumors such as osteosarcomas.
It seems reasonable to assume that the initial cross-disciplinary cooperation between physicians -- so far only experienced in the prostate cancer field -- will become a cornerstone of future cancer therapy.
Elisa Borsò as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Division of Nuclear Medicine, University Hospital of Pisa, Pisa, Italy