Vivek K. Wadhwa

Long-term changes in bone mineral density and predicted fracture risk in patients receiving androgen-deprivation therapy for prostate cancer, with stratification of treatment based on presenting values

To study the long‐term effects of androgen‐deprivation therapy (ADT) using luteinizing hormone‐releasing hormone (LHRH) agonists or antiandrogen therapy with bicalutamide on bone mineral density (BMD) of selected groups of patients with newly diagnosed advanced prostate cancer, stratified by BMD at presentation and to predict alterations in fracture risk.

Bicalutamide monotherapy preserves bone mineral density, muscle strength and has significant health‐related quality of life benefits for osteoporotic men with prostate cancer

Study Type – Therapy (case series)

Frequency of zoledronic acid to prevent further bone loss in osteoporotic patients undergoing androgen deprivation therapy for prostate cancer

Study Type – Therapy (RCT)
Level of Evidence 1b

Peripheral or Axial Bone Density Measurements to Identify Osteoporosis in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy

OBJECTIVES To compare aDEXA and pDEXA in patients with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). A significant proportion of patients presenting with advanced PCa are osteoporotic, and many will become so because of ADT. Guidelines have recommended bone densitometry assessment before beginning ADT, with subsequent monitoring. However, axial dual energy x-ray absorptiometry (aDEXA) scanners, being large, expensive, and hospital-based, are not always widely available. Peripheral DEXA (pDEXA), with portable, office-based machines can be used, but the results have mostly been compared with aDEXA in women without cancer. METHODS A total of 73 men (mean age 76 years) with advanced PCa, who were receiving ADT and found to be osteoporotic (T score <or=-2.5) on pDEXA (Osteometer-DTX200) were also scanned by aDEXA (Hologic-QDR 4500 DEXA). Comparisons were made between the bone mineral density measurements of the ultradistal forearm and axial sites. RESULTS The mean +/- SD T score of the forearm, femoral neck, total hip, and lumbar spine was -3.4 +/- 0.8, -2.6 +/- 1.0, -1.8 +/- 0.9, and -0.8 +/- 1.3, respectively. Of the 73 men, 67, 61, and 39 were found to be osteoporotic or osteopenic at the femoral neck, total hip, and lumbar spine, respectively. The correlation coefficients between the forearm and axial T scores were all significant (P < .05): femoral neck, r = 0.32, total hip, r = 0.34, lumbar spine, r = 0.24. CONCLUSIONS When osteoporosis is diagnosed on pDEXA, most patients with PCa will be either osteoporotic or osteopenic at the hip, but a large proportion will be normal at the lumbar spine. In this setting, lumbar DEXA might be less reliable at predicting the fracture risk probably owing to calcification and degenerative changes.

Lateral Spine Radiographs Before Androgen Deprivation Treatment Detect a High Incidence of Undiagnosed Vertebral Fragility Fractures in Men With Advanced Prostate Cancer

PURPOSE Baseline bone mineral density scanning in patients about to commence long-term androgen deprivation therapy for advanced/metastatic prostate cancer is reported to show a high incidence of osteoporosis and osteopenia. We investigated the incidence of existing spinal osteoporotic fractures in this population as this is known to be a risk factor for the development of treatment induced fractures. MATERIALS AND METHODS Since 2003 we performed lateral thoracolumbar x-rays on all patients before androgen deprivation therapy for prostate cancer. The heights of T4-L5 vertebral bodies were measured, then reanalyzed by the Eastell method to define grade 1 or worse grade 2 vertebral crush fractures. We used a morphometric algorithm including an age stratified random sample of men with normal thoracolumbar x-rays to quantitatively assess fractures. RESULTS A total of 202 patients with prostate cancer underwent thoracolumbar x-rays before androgen deprivation therapy. Of the patients 61.9% had 1 or more grade 1 and 60.9% had 1 or more grade 2 wedge fractures. In addition, 46.5% of patients had 1 or more grade 1 and 44.6% had greater than 1 grade 2 biconcavity fractures. Finally 63.9% of patients had 1 or more grade 1 and 47.8% had 1 or more grade 2 compression fractures. With conventional reporting 72.4% of patients had no bony abnormality, 14.9% had 1 and 12.7% multiple vertebral crush fractures. Bone mineral density was significantly less in patients with fracture(s) vs those with no abnormality (p<0.001). CONCLUSIONS Routine reporting identifies a high incidence of spinal fractures before commencing androgen deprivation therapy, but this is much greater when quantitative assessment is applied. Thoracolumbar x-rays identify the risk of treatment induced fracture and allow baseline comparison in individuals who experience back pain on androgen deprivation therapy. We advocate more routine adoption of baseline thoracolumbar x-rays in patients with prostate cancer.

Lateral spine radiographs prior to androgen deprivation treatment detect a high incidence of undiagnosed vertebral fragility fractures in advanced prostate cancer

Introduction: There is a paucity of data invesigating the relationship between histopathological ariables of oncologic importance and prostate volme, and we aimed to investigate this. Patients and methods: 2207 consecutive atients who underwent robotic-assisted radical rostatectomy (RARP) were studied. Preoperative emographic and both preand post-operative istopathological parameters were compared mong the small prostate (<40 cc), intermediate ize (40—70 cc), and large prostate (>70 cc) groups. Results: Patients with smaller prostates were ounger, had slightly lower BMIs, and lower PSAs han those with larger prostates (p < 0.001). They lso had worse histopathological criteria (Gleaon, core positivity, and maximum percent cancer) n preoperative biopsy and had worse radical pecimen Gleason sums (p < 0.001), percent caner (p < 0.001), and pathological stage (p = 0.016). 1.5% of men in the small prostate group suffered positive surgical margin (PSM) compared to 8.3% nd 5.6% in the intermediate and large prostate roups, respectively (p = 0.008). Basilar, posterolatral, and multifocal PSMs were commoner in the mall prostate group. Conclusions: Younger men have smaller prostates nd worse preoperative histopathological parameers despite lower PSAs. Men with small prostates ndergoing RARP have worse final Gleason sums, umour volume, extraprostatic extension (EPE), nd PSM rates than those with larger prostates.

A Large Proportion of Patients with Prostate Cancer Undergoing Androgen Deprivation Therapy Continue to Die from Non-Cancer Causes in the PSA Era

Objective: This study was conducted to determine the cause of death in patients receiving ADT for PCa in the PSA era. Patients and methods: We followed 618 patients (mean age 73 years) with PCa initiating ADT from October 1999 to October 2007. Patients were recruited from urology clinics. Patients were regularly reviewed in a dedicated PCa clinic. Cause of death was recorded prospectively, after review of medical case notes and biochemical parameters. Results: At median follow-up of 6.7 years, there were 377 deaths (61% mortality). Of these, 176 (47%) were attributable to PCa. Non-cancer deaths (n = 201) were predominantly cardiovascular (n = 125) and respiratory (n = 43). Overall median presenting PSA was 37 ng/ml (range 0.4–5599), significantly higher (P < 0.001) in those dying from PCa (115 ng/ml) than from other causes (18 ng/ml). PCa specific mortality increased with PSA at presentation (14% for PSA < 50 ng/ml, 45% for 50–100 ng/ml and 69% for > 100 ng/ml). When stratified for presenting age, PCa deaths were 70% (46/66) for men 60–69 years, 47% (85/180) for 70–79 years and 34% (45/131) for >80 years. Conclusions: Many patients with PCa initiating ADT continue to die from non-cancer causes in an era of widespread PSA testing, the proportion increasing with older age at presentation. This may justify deferring hormonal treatment in suitable older asymptomatic men, sparing the burden of long-term ADT. Patients with PCa who require hormonal therapy should be assessed for cardiovascular and respiratory risk factors at the time of presentation.