Role of denosumab in prostate cancer.

Prostate cancer is known to have a tissue tropism for bone. This tissue tropism coupled with the experience with androgen deprivation therapy (ADT) over the past decade has led to heightened awareness of bone complications. Osteopenia and subsequent skeletal-related events (SREs) are one of the more concerning repercussions of ADT along with cardiovascular sequelae. To combat this decrease in bone mineral density, several agents have been developed for bone protection. The largest experience is with bisphosphonates (BPs), but recently (2011) head to head trials have established the role of monoclonal antibodies, particularly in patients with prostate cancer bone metastasis. For patients initiating ADT, monthly denosumab increased bone mineral density, the time for occurrence of any bone metastasis and time for symptomatic bone metastasis. Denosumab is a fully human monoclonal antibody of the IgG(2) subtype that selectively binds and neutralizes receptor activator NF kappa B ligand (RANKL), inhibiting osteoclastogenesis and bone turnover. In vitro binding assays have shown high-affinity binding of denosumab and osteoprotegerin to both soluble and membrane-bound forms of human RANKL. As clinicians may be less familiar with this newer agent, we compiled this review to summarize denosumab's current clinical indications for bone stabilization and mechanism of reduction in tumor burden.

Construct validity in a high-fidelity prostate exam simulator.

BACKGROUND: All health care practitioners should be facile in the digital rectal exam (DRE) as it provides prostate, rectal and neurological information. The purpose of this study was first to justify our hypothesis that tissue elasticity is indicative of carcinomatous changes. Second, we employed urological surgeons to evaluate our prostate simulator in three ways: (1) authenticate that the elasticity of the simulated prostates accurately represents the range of normal prostate stiffness, (2) determine the range of nodule size reasonably palpable by DRE and (3) discern what degree of elasticity difference within the same prostate suggests malignancy. METHODS: Institutional Review Board-approved materials characterization, human-subjects experiments, histopathology and chart abstraction of clinical history were performed. Material characterization of 21 ex-vivo prostatectomy specimens was evaluated using a custom-built, portable spherical indentation device while a novel prostate simulator was employed to measure human-subject perception of prostatic state. RESULTS: From the materials characterization, the measurements of the 21 gross prostates and 40 cross-sections yielded 306 data points. Within the same prostate, cancer was always stiffer. Of the seven cases with an abnormal DRE, the DRE accurately identified adenocarcinoma in 85%. From the human-subjects experiments, the simulated prostates evaluated by urologists ranged in stiffness from 8.9 to 91 kPa, mimicking the range found on ex vivo analysis of 4.6-236.7 kPa. The urological surgeons determined the upper limit of stiffness palpated as realistic for a healthy prostate was 59.63 kPa while the lower limit of stiffness was 27.1 kPa. Nodule size less than 7.5 mm was felt to be too small to reasonably palpate. CONCLUSIONS: We found it is not the absolute elasticity of the nodule, but rather the relationship of the nodule with the background prostate elasticity that constitutes the critical tactile feedback. Prostate simulator training may lead to greater familiarity with pertinent diagnostic cues and diagnosis of prostate cancer.

Concordance in the perception of couples recovering from primary surgical treatment of prostate cancer.

Although prostate cancer affects men, research shows effects on both members of the couple. We analyzed concordance in couples recovering from primary surgical treatment of prostate cancer when surveyed on psychological domains including emotional status, relationship, self-image, partnership quality and support. Retrospective Sexual Surveys were utilized to survey physiological changes as well as psychological effects. In total, 28 heterosexual couples (56 people) were enrolled. Patients were treated between February 2002 and March 2007 with a median follow-up of 26 (range: 4-59) months. When polled on psychological aspects that may have been affected by treatment, overall concordance was 75.0%. Partnership had the highest concordance (92.2%) with treatment satisfaction questions following in second (90.7%). Subcategories focused on self-image (77.5%), relationship (67.3%), support (66.4%) and emotional status (55.6%), were less concordant. Although couples report relationships as strong and team-like, misconception between partners is widespread. Further research with regards to the effect of such disparities in couples might provide additional insight into improving recovery.

Sociodemographic factors associated with postprostatectomy radiotherapy.

PURPOSE: To determine if nonclinical factors affect the use of adjuvant radiation therapy after surgical resection of the prostate gland. METHODS: Using the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) public use data files, we identified men with localized/regional prostate cancer who underwent postprostatectomy radiotherapy within 4 months of surgery. We used 2000 Census information to ascribe a median education and income level to these men based on the county of residence and ethnicity. RESULTS: Of 34,763 men who underwent surgical resection, 1549 received postprostatectomy radiotherapy. Those with higher tumor grade and from certain geographic regions (Seattle and Hawaii) had significantly higher rates of radiotherapy while being older and from other geographic regions (Detroit, Utah, and New Mexico) was protective. The use of additional radiation therapy was not affected by ethnicity, income level, or educational attainment. CONCLUSIONS: We found no socioeconomic or demographic disparities in the receipt of postprostatectomy radiotherapy. Geographic variation in postprostatectomy radiotherapy may be explained by limited evidence supporting its use in clinical practice.

The effect of sampling more cores on the predictive accuracy of pathological grade and tumour distribution in the prostate biopsy.

OBJECTIVE: To determine if increasing the number of cores at biopsy improves the predictive accuracy of the Gleason score or aids in anticipating the location and volume of prostate tumour. PATIENTS AND METHODS: The charts of 75 consecutive patients who underwent radical retropubic prostatectomy for clinical T1-2 adenocarcinoma of the prostate were reviewed retrospectively; 31 patients had a sextant biopsy (group 1) and 44 had > or = 8 cores taken (group 2). The concordance between biopsy data and final prostatectomy Gleason score, tumour location and volume was determined for each group. RESULTS: There were no differences in mean age, prostate-specific antigen level before biopsy or biopsy Gleason score for the two groups; 58% of group 1 had their final pathological grade changed after prostatectomy, vs 29% of group 2 (P < 0.05). In neither group was there a significant correlation between the percentage of cores positive for tumour and the percentage volume of prostate involved with cancer, or the ability of the biopsy to predict tumour location. CONCLUSION: Taking > or = 8 biopsy cores improved the pathological grading accuracy, which may be valuable in choosing a treatment for the patient with newly diagnosed prostate cancer.

Radioactive implant migration in patients treated for localized prostate cancer with interstitial brachytherapy.

PURPOSE: In several of the initial patients undergoing brachytherapy at our institution radioactive implants were visible in the thorax on chest radiography. The clinical ramifications of this unanticipated finding were unclear. Thus, we investigated the incidence of brachytherapy seed migration to the chest and whether these seeds were associated with any clinical significance. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent ultrasound or computerized tomography guided brachytherapy of 103palladium seeds from March 1997 to March 1999. This list of patients on brachytherapy was then matched against the radiology computer system to determine those who had undergone chest X-ray after brachytherapy. When the radiology report was unclear regarding brachytherapy seeds, chest x-rays were reviewed by one of us (R. O.) to determine the presence and position of the seeds. RESULTS: Post-brachytherapy chest x-rays were available in 110 of the 183 patients. In 78 cases no brachytherapy seeds were identified. Radioactive implants were identified on chest radiography in 32 patients (29%), including 1 to 5 seeds in 20, 8, 1, 2 and 1, respectively. No patients complained of any change in pulmonary symptoms after brachytherapy. CONCLUSIONS: Radioactive implants migrated after brachytherapy for localized prostate cancer in 29% of the patients who underwent post-procedure radiography. There did not appear to be a pattern to the seed distribution. However, while the incidence was not negligible, no patient appeared to have any acute pulmonary symptoms. Therefore, while the migration of radioactive implants to the chest is a real phenomenon, it appears to have no adverse clinical consequences in the early post-procedure period.