Marianne Schmid

Zoledronic Acid Prevents Cancer Treatment–Induced Bone Loss in Premenopausal Women Receiving Adjuvant Endocrine Therapy for Hormone-Responsive Breast Cancer: A Report From the Austrian Breast and Colorectal Cancer Study Group

PURPOSE Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients. PATIENTS AND METHODS This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) +/- zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin +/- zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months. RESULTS Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, -14.4% after 36 months; mean T score reduction, -1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, -17.3%; mean T score reduction, -2.6) compared with patients receiving tamoxifen/goserelin (BMD, -11.6%; mean T score reduction, -1.1). In contrast, BMD remained stable in zoledronic acid-treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted. CONCLUSION Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.

Randomized trial of tamoxifen versus tamoxifen plus aminoglutethimide as adjuvant treatment in postmenopausal breast cancer patients with hormone receptor-positive disease: Austrian breast and colorectal cancer study group trial 6.

PURPOSE To determine whether the addition of aminoglutethimide to tamoxifen is able to improve the outcome in postmenopausal patients with hormone receptor-positive, early-stage breast cancer. PATIENTS AND METHODS A total of 2,021 postmenopausal women were randomly assigned to receive either tamoxifen for 5 years alone or tamoxifen in combination with aminoglutethimide (500 mg/d) for the first 2 years of treatment. Tamoxifen was administered at 40 mg/d for the first 2 years and at 20 mg/d for 3 years. RESULTS All randomized and eligible patients were included in the analysis according to the intention-to-treat principle. After a median follow-up of 5.3 years, the 5-year disease-free survival in the aminoglutethimide plus tamoxifen group was 83.6% versus 83.7% in the monotherapy group (P =.89). The corresponding data for overall survival at 5 years were 91.4% and 91.2%, respectively (P =.74). More patients failed to complete combination treatment (13.7%) because of side effects as compared to tamoxifen alone (5.2%; P =.0001). CONCLUSION Aminoglutethimide given for 2 years in addition to tamoxifen for 5 years does not improve the prognosis of postmenopausal patients with receptor-positive, lymph node-negative or lymph node-positive breast cancer.

The Relationship between Total Testosterone Levels and Prostate Cancer: A Review of the Continuing Controversy

PURPOSE For many years it was believed that higher total testosterone contributed to prostate cancer and caused rapid cancer growth. International guidelines consider that adequate data are not available to determine whether there is additional risk of prostate cancer from testosterone replacement. Numerous studies with multiple designs and contradictory conclusions have investigated the relationship between total testosterone and prostate cancer development. To establish current knowledge in this field we reviewed the literature on total testosterone and the subsequent risk of prostate cancer as well as the safety of exogenous testosterone administration in patients with a history of prostate cancer. MATERIALS AND METHODS We searched the literature to identify articles from 1994 to 2014 related to the relationship between total testosterone and prostate cancer. Emphasis was given to prospective studies, series with observational data and randomized, controlled trials. Case reports were excluded. Articles on testosterone replacement safety were selected by patient population (under active surveillance or with a prostate cancer history). We organized our results according to the relationship between total testosterone and prostate cancer, including 1) the possible link between low total testosterone and prostate cancer, 2) the effect of high levels and 3) the absence of any link. Finally, we summarized studies of the risk of exogenous testosterone administration in patients already diagnosed with prostate cancer, treated or on active surveillance. RESULTS We selected 45 articles of the relationship between total testosterone and prostate cancer, of which 18 and 17 showed a relationship to low and high total testosterone, respectively, and 10 showed no relation. Total testosterone was defined according to the definition in each article. Contradictory findings have been reported, largely due to the disparate methodologies used in many studies. Most studies did not adhere to professional society guidelines on total testosterone measurements. One of 18 series of low total testosterone and prostate cancer adhered to published guidelines while none of 17 showing a relationship of high total testosterone to prostate cancer and only 1 of 10 that identified no relationship between total testosterone and prostate cancer adhered to measurements recommended in the guidelines. In 11 studies the risk of exogenous testosterone was examined in patients with a prostate cancer history. Many studies were limited by small cohort size and brief followup. However, overall this literature suggests that the risk of exogenous testosterone replacement in patients with prostate cancer appears to be small. CONCLUSIONS The relationship between total testosterone and prostate cancer has been an area of interest among physicians for decades. Conflicting results have been reported on the relationship between total testosterone and subsequent prostate cancer. Much of this controversy appears to be based on conflicting study designs, definitions and methodologies. To date no prospective study with sufficient power has been published to unequivocally resolve the issue. The preponderance of studies of the safety of exogenous testosterone in men with a prostate cancer history suggests that there is little if any risk. However, because the risk has not proved to be zero, the most prudent course is to follow such men with regular prostate specific antigen measurements and digital rectal examinations.

The impact of resident involvement in minimally-invasive urologic oncology procedures

INTRODUCTION Robotic and laparoscopic surgical training is an integral part of resident education in urology, yet the effect of resident involvement on outcomes of minimally-invasive urologic procedures remains largely unknown. We assess the impact of resident participation on surgical outcomes using a large multi-institutional prospective database. METHODS Relying on the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Participant User Files (2005-2011), we abstracted the 3 most frequently performed minimally-invasive urologic oncology procedures. These included radical prostatectomy, radical nephrectomy and partial nephrectomy. Multivariable logistic regression models were constructed to assess the impact of trainee involvement (PGY 1-2: junior, PGY 3-4: senior, PGY ≥5: chief) versus attending-only on operative time, length-of-stay, 30-day complication, reoperation and readmission rates. RESULTS A total of 5459 minimally-invasive radical prostatectomies, 1740 minimally-invasive radical nephrectomies and 786 minimally-invasive partial nephrectomies were performed during the study period, for which data on resident surgeon involvement was available. In multivariable analyses, resident involvement was not associated with increased odds of overall complications, reoperation, or readmission rates for minimally-invasive prostatectomy, radical and partial nephrectomy. However, operative time was prolonged when residents were involved irrespective of the type of procedure. Length-of-stay was decreased with senior resident involvement in minimally-invasive partial nephrectomies (odds ratio [OR] 0.49, p = 0.04) and prostatectomies (OR 0.68, p = 0.01). The major limitations of this study include its retrospective observational design, inability to adjust for the case complexity and surgeon/hospital characteristics, and the lack of information regarding the minimally-invasive approach utilized (whether robotic or laparoscopic). CONCLUSIONS Resident involvement is associated with increased operative time in minimally-invasive urologic oncology procedures. However, it does not adversely affect the complication, reoperation or readmission rates, as well as length-of-stay.

Racial Differences in the Surgical Care of Medicare Beneficiaries With Localized Prostate Cancer

IMPORTANCE There is extensive evidence suggesting that black men with localized prostate cancer (PCa) have worse cancer-specific mortality compared with their non-Hispanic white counterparts. OBJECTIVE To evaluate racial disparities in the use, quality of care, and outcomes of radical prostatectomy (RP) in elderly men (≥ 65 years) with nonmetastatic PCa. DESIGN, SETTING, AND PARTICIPANTS This retrospective analysis of outcomes stratified according to race (black vs non-Hispanic white) included 2020 elderly black patients (7.6%) and 24,462 elderly non-Hispanic white patients (92.4%) with localized PCa who underwent RP within the first year of PCa diagnosis in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 1992 and 2009. The study was performed in 2014. MAIN OUTCOMES AND MEASURES Process of care (ie, time to treatment, lymph node dissection), as well as outcome measures (ie, complications, emergency department visits, readmissions, PCa-specific and all-cause mortality, costs) were evaluated using Cox proportional hazards regression. Multivariable conditional logistic regression and quantile regression were used to study the association of racial disparities with process of care and outcome measures. RESULTS The proportion of black patients with localized prostate cancer who underwent RP within 90 days was 59.4% vs 69.5% of non-Hispanic white patients (P <  001). In quantile regression of the top 50% of patients, blacks had a 7-day treatment delay compared with non-Hispanic whites. (P <  001). Black patients were less likely to undergo lymph node dissection (odds ratio [OR], 0.76 [95% CI, 0.66-0.80]; P < .001) but had higher odds of postoperative visits to the emergency department (within 30 days: OR, 1.48 [95% CI, 1.18-1.86]); after 30 days or more (OR, 1.45 [95% CI, 1.19-1.76]) and readmissions (within 30 days: OR, 1.28 [95% CI, 1.02-1.61]); ≥ 30 days (OR, 1.27 [95% CI, 1.07-1.51]) compared with non-Hispanic whites. The surgical treatment of black patients was associated with a higher incremental annual cost (the top 50% of blacks spent

Effect of minimally invasive surgery on the risk for surgical site infections: results from the National Surgical Quality Improvement Program (NSQIP) Database.

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Getting back to equal: The influence of insurance status on racial disparities in the treatment of African American men with high-risk prostate cancer.

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Gamma knife radiosurgery and albendazole for cerebral alveolar hydatid disease.

1566.10; P < .001) more than the top 50% of non-Hispanic whites). There was no difference in PCa-specific mortality (P = .16) or all-cause mortality (P = .64) between black and non-Hispanic white men. CONCLUSIONS AND RELEVANCE Blacks treated with RP for localized PCa are more likely to experience adverse events and incur higher costs compared with non-Hispanic white men; however, this does not translate into a difference in PCa-specific or all-cause mortality.

Morbidity and mortality after benign prostatic hyperplasia surgery: data from the American College of Surgeons national surgical quality improvement program.

IMPORTANCE Surgical site infection (SSI) represents the second most common cause of hospital-acquired infection and the most common type of infection in patients undergoing surgery. However, evidence is scarce regarding the effect of the surgical approach (open surgery vs minimally invasive surgery [MIS]) on the risk for SSIs. OBJECTIVE To evaluate the role of the surgical approach on the risk for SSIs in a large contemporary cohort of patients undergoing surgery across different specialties. DESIGN, SETTING, AND PARTICIPANTS The American College of Surgeons National Surgical Quality Improvement Program database is a national, prospective perioperative database specifically developed to assess quality of surgical care. We queried the database from January 1, 2005, through December 31, 2011, for patients undergoing appendectomy (n = 97,780), colectomy (n = 118,407), hysterectomy (n = 26,639), or radical prostatectomy (n = 11,183). EXPOSURES Thirty-day SSIs. MAIN OUTCOMES AND MEASURES We abstracted the data on 30-day SSIs and compared patients undergoing open procedures and MIS using propensity score matching. Logistic regression analyses of the matched cohorts tested the association between the surgical approach and risk for SSIs. RESULTS The overall 30-day rates of SSIs were 5.4% for appendectomy, 12.1% for colectomy, 2.8% for hysterectomy, and 1.7% for prostatectomy. After propensity score matching, MIS was associated with lower rates of postoperative SSIs in patients undergoing MIS vs open procedures for appendectomy (3.8% vs 7.0%; P < .001), colectomy (9.3% vs 15.0%; P < .001), hysterectomy (1.8% vs 3.9%; P < .001), and radical prostatectomy (1.0% vs 2.4%; P < .001). In logistic regression analyses, MIS was associated with lower odds of SSIs in patients treated with appendectomy (odds ratio [OR], 0.52 [95% CI, 0.48-0.58]; P < .001), colectomy (OR, 0.58 [95% CI, 0.55-0.61]; P < .001), hysterectomy (OR, 0.44 [95% CI, 0.37-0.53]; P < .001), and radical prostatectomy (OR, 0.39 [95% CI, 0.25-0.61]; P < .001). CONCLUSIONS AND RELEVANCE The proportion of patients developing SSIs within 30 days after surgery can be substantial and depends on the type of surgery. Minimally invasive surgery is significantly associated with reduced odds of SSIs. This advantage should be considered when assessing the overall benefits of minimally invasive techniques.

Cancer-Specific Mortality of Asian Americans Diagnosed With Cancer: A Nationwide Population-Based Assessment

OBJECTIVES Treating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP. MATERIALS AND METHODS The Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level > 20 ng/ml or Gleason score 8-10 or stage > cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy. RESULTS Compared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] = 0.60; 95% CI: 0.56-0.64; P < 0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status (P interaction = 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27-0.54, P < 0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57-0.66, P < 0.001) among insured men. CONCLUSIONS AA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers.