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Background: Kidney cancer incidence demonstrates significant geographic variation suggesting a role for environmental risk factors. This study sought to evaluate associations between groundwater exposures and kidney cancer incidence. Methods: The authors identified constituents from 18,506 public groundwater wells in all 58 California counties measured in 1996–2010, and obtained county‐level kidney cancer incidence data from the California Cancer Registry for 2003–2017. The authors developed a water‐wide association study (WWAS) platform using XWAS methodology. Three cohorts were created with 5 years of groundwater measurements and 5‐year kidney cancer incidence data. The authors fit Poisson regression models in each cohort to estimate the association between county‐level average constituent concentrations and kidney cancer, adjusting for known risk factors: sex, obesity, smoking prevalence, and socioeconomic status at the county level. Results: Thirteen groundwater constituents met stringent WWAS criteria (a false discovery rate <0.10 in the first cohort, followed by p values <.05 in subsequent cohorts) and were associated with kidney cancer incidence. The seven constituents directly related to kidney cancer incidence (and corresponding standardized incidence ratios) were chlordane (1.06; 95% confidence interval [CI], 1.02–1.10), dieldrin (1.04; 95% CI, 1.01–1.07), 1,2‐dichloropropane (1.04; 95% CI, 1.02–1.05), 2,4,5‐TP (1.03; 95% CI, 1.01–1.05), glyphosate (1.02; 95% CI, 1.01–1.04), endothall (1.02; 95% CI, 1.01–1.03), and carbaryl (1.02; 95% CI, 1.01–1.03). Among the six constituents inversely related to kidney cancer incidence, the standardized incidence ratio furthest from the null was for bromide (0.97; 95% CI, 0.94–0.99). Conclusions: This study identified several groundwater constituents associated with kidney cancer. Public health efforts to reduce the burden of kidney cancer should consider groundwater constituents as environmental exposures that may be associated with the incidence of kidney cancer. This study analyzed 180 groundwater exposures in California and used a water‐wide association study (WWAS) platform, based on XWAS methodology, to identify associations between groundwater exposures and kidney cancer incidence. Results revealed 13 groundwater constituents meeting stringent WWAS criteria, with seven directly linked to increased kidney cancer incidence, suggesting that public health efforts should consider environmental exposures that may be associated with the incidence of kidney cancer. [ABSTRACT FROM AUTHOR]

Patients with kidney stone disease are at higher risk for bone disease. Hypocitraturia is common in patients with kidney stone disease and a key risk factor for stone recurrence. In this retrospective cohort study, we sought to determine whether hypocitraturia is also a risk factor for incident bone disease in patients with kidney stone disease. We used nationwide data from the Veterans Health Administration and identified 9025 patients with kidney stone disease who had a 24‐hour urine citrate measurement between 2007 and 2015. We examined clinical characteristics of patients by level of 24‐hour urine citrate excretion (<200, 200–400, and >400 mg/d) and the time to osteoporosis or fracture according to 24‐hour urine citrate excretion level. Almost one in five veterans with kidney stone disease and a 24‐hour urine citrate measurement had severe hypocitraturia, defined as <200 mg/d. Patients with severe hypocitraturia were at risk for osteoporosis or fracture (hazard ratio [HR] = 1.23; confidence interval [CI] 1.03–1.48), but after adjustment for demographic factors, comorbid conditions, and laboratory abnormalities associated with hypocitraturia, the association was no longer statistically significant (HR = 1.18; CI 0.98–1.43). Our results in a predominantly male cohort suggest a modest association between hypocitraturia and osteoporosis or fracture; there are likely to be other explanations for the potent association between kidney stone disease and diminished bone health. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Background: Factors that influence prostate cancer treatment decisions are complex, multifaceted, and personal, and may vary by race/ethnicity. Although research has been published to quantify factors involved in decision‐making, these studies have been limited to primarily white, and to a lesser extent, Black patients, and quantitative studies are limited for discerning the cultural and contextual processes that shape decision‐making. Methods: We conducted 43 semi‐structured interviews with a racially and ethnically diverse sample of patients diagnosed with low‐ and very‐low risk prostate cancer who had undergone treatment for their prostate cancer. Interviews were transcribed, independently coded, and analyzed to identify themes salient for decision‐making, with attention to sociocultural differences. Results: We found racial and ethnic differences in three areas. First, we found differences in how socialized masculinity influenced patient's feelings about different treatment options. Second, we found that for some men, religion and spirituality alleviated anxiety associated with the active surveillance protocol. Finally, for racially and ethnically minoritized patients, we found descriptions of how historic and social experiences within the healthcare system influenced decision‐making. Conclusions: Our study adds to the current literature by expounding on racial and ethnic differences in the multidimensional, nuanced factors related to decision‐making. Our findings suggest that factors associated with prostate cancer decision‐making can manifest differently across racial and ethnic groups, and provide some guidance for future research. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated that Black men may undergo definitive prostate cancer (CaP) treatment less often than men of other races, but it is unclear whether they are avoiding overtreatment of low‐risk disease or experiencing a reduction in appropriate care. The authors' aim was to assess the role of race as it relates to treatment benefit in access to CaP treatment in a single‐payer population. Methods: The authors used the Veterans Health Administration (VHA) Corporate Data Warehouse to perform a retrospective cohort study of veterans diagnosed with low‐ or intermediate‐risk CaP between 2011 and 2017. Results: The authors identified 35,427 men with incident low‐ or intermediate‐risk CaP. When they controlled for covariates, Black men had 1.05 times the odds of receiving treatment in comparison with non‐Black men (P <.001), and high‐treatment‐benefit men had 1.4 times the odds of receiving treatment in comparison with those in the low‐treatment‐benefit group (P <.001). The interaction of race and treatment benefit was significant, with Black men in the high‐treatment‐benefit category less likely to receive treatment than non‐Black men in the same treatment category (odds ratio, 0.89; P <.001). Conclusions: Although race does appear to influence the receipt of definitive treatment in the VHA, this relationship varies in the context of the patient's treatment benefit, with Black men receiving less definitive treatment in high‐benefit situations. The influence of patient race at high treatment benefit levels invites further investigation into the driving forces behind this persistent disparity in this consequential group. Race appears to influence the receipt of definitive treatment in the Veterans Health Administration, and this relationship varies in the context of the patient's treatment benefit, with Black men receiving less definitive treatment in high‐benefit situations. The influence of patient race at high treatment benefit levels invites further investigation into the driving forces behind this persistent disparity in this consequential group. [ABSTRACT FROM AUTHOR]

Whether a link exists between kidney stone disease and osteoporosis or fractures remains an open question. In this retrospective cohort study, we sought to determine the prevalence of osteoporosis and fractures and rate of bone mineral density screening by dual‐energy X‐ray absorptiometry (DXA) in patients with kidney stone disease. We examined nationwide data from the Veterans Health Administration and identified 531,431 patients with kidney stone disease between 2007 and 2015. Nearly 1 in 4 patients (23.6%, 95% confidence interval [CI] 23.5–23.7) with kidney stone disease had a prevalent diagnosis of osteoporosis or fracture. In patients with no prior history of osteoporosis or bone mineral density assessment before a kidney stone diagnosis, 9.1% were screened with DXA after their kidney stone diagnosis, of whom 20% were subsequently diagnosed with osteoporosis. Our findings provide support for wider use of bone mineral density screening in patients with kidney stone disease, including middle‐aged and older men, a group less well recognized as at risk for osteoporosis or fractures. © 2021 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Background: Estimates of overall patient health are essential to inform treatment decisions for patients diagnosed with cancer. The authors applied XWAS methods, herein referred to as "laboratory‐wide association study (LWAS)", to evaluate associations between routinely collected laboratory tests and survival in veterans with prostate cancer. Methods: The authors identified 133,878 patients who were diagnosed with prostate cancer between 2000 and 2013 in the Veterans Health Administration using any laboratory tests collected within 6 months of diagnosis (3,345,083 results). Using the LWAS framework, the false‐discovery rate was used to test the association between multiple laboratory tests and survival, and these results were validated using training, testing, and validation cohorts. Results: A total of 31 laboratory tests associated with survival met stringent LWAS criteria. LWAS confirmed markers of prostate cancer biology (prostate‐specific antigen: hazard ratio [HR], 1.07 [95% confidence interval (95% CI), 1.06‐1.08]; and alkaline phosphatase: HR, 1.22 [95% CI, 1.20‐1.24]) as well laboratory tests of general health (eg, serum albumin: HR, 0.78 [95% CI, 0.76‐0.80]; and creatinine: HR, 1.05 [95% CI, 1.03‐1.07]) and inflammation (leukocyte count: HR, 1.23 [95% CI, 1.98‐1.26]; and erythrocyte sedimentation rate: HR, 1.33 [95% CI, 1.09‐1.61]). In addition, the authors derived and validated separate models for patients with localized and advanced disease, identifying 28 laboratory markers and 15 laboratory markers, respectively, in each cohort. Conclusions: The authors identified routinely collected laboratory data associated with survival for patients with prostate cancer using LWAS methodologies, including markers of prostate cancer biology, overall health, and inflammation. Broadening consideration of determinants of survival beyond those related to cancer itself could help to inform the design of clinical trials and aid in shared decision making. Lay Summary: This article examined routine laboratory tests associated with survival among veterans with prostate cancer.Using laboratory‐wide association studies, the authors identified 31 laboratory tests associated with survival that can be used to inform the design of clinical trials and aid patients in shared decision making. The current study identifies common clinical laboratory tests that are associated with mortality in patients with prostate cancer. These tests may aid in the challenging task of estimating life expectancy among men with prostate cancer, among whom overdiagnosis is common and in whom competing risks of mortality dominate prostate cancer–specific mortality risk. [ABSTRACT FROM AUTHOR]

Background: Although prostate‐specific antigen (PSA) testing is used for prostate cancer detection and posttreatment surveillance, thresholds in these settings differ. The screening cutoff of 4.0 ng/mL may be inappropriately used during postsurgery surveillance, where 0.2 ng/mL is typically used, creating missed opportunities for effective salvage radiation treatment. We performed a study to determine whether guideline concordance with annual postoperative PSA surveillance increases when PSA values exceed 4 ng/mL, which represents a screening threshold that is not relevant after surgery. Methods: We used US Veterans Health Administration data to perform a retrospective longitudinal cohort study of men diagnosed with nonmetastatic prostate cancer from 2005 to 2008 who underwent radical prostatectomy. We used logistic regression to examine the association between postoperative PSA levels and receipt of an annual PSA test. Results: Among 10 400 men and 38 901 person‐years of follow‐up, annual guideline concordance decreased from 95% in year 1 to 79% in year 7. After adjustment, guideline concordance was lower for the youngest and oldest men, Black, and unmarried men. Guideline concordance significantly increased as PSA exceeded 4 ng/mL (adjusted odds ratio 2.20 PSA > 4‐6 ng/mL vs PSA > 1‐4 ng/mL, 95% confidence interval 1.20‐4.03; P =.01). Conclusions: Guideline concordance with prostate cancer surveillance increased when PSA values exceeded 4 ng/mL, suggesting a screening threshold not relevant after prostate cancer surgery, where 0.2 ng/mL is considered treatment failure, is impacting cancer surveillance quality. Clarification of PSA thresholds for early detection vs cancer surveillance, as well as emphasizing adherence for younger and Black men, appears warranted. [ABSTRACT FROM AUTHOR]

Objectives: To characterise bone scan use, and potential overuse, after radical prostatectomy (RP) using data from a large, national integrated delivery system. Overuse of imaging is well documented in the setting of newly diagnosed prostate cancer, but whether overuse persists after RP remains unknown. Patients and methods: We identified 12 269 patients with prostate cancer treated with RP between 2005 and 2008 using the Veterans Administration Central Cancer Registry. We used administrative and laboratory data to examine rates of bone scan use, including preceding prostate‐specific antigen (PSA) levels, and receipt of adjuvant or salvage therapy. We then performed multivariable logistic regression to identify factors associated with post‐RP bone scan use. Results: At a median follow‐up of 6.8 years, one in five men (22%) underwent a post‐RP bone scan at a median PSA level of 0.2 ng/mL. Half of bone scans (48%) were obtained in men who did not receive further treatment with androgen‐deprivation or radiation therapy. After adjustment, post‐RP bone scan was associated with a prior bone scan (adjusted odds ratio [aOR] 1.55, 95% confidence interval [CI] 1.32–1.84), positive surgical margin (aOR 1.68, 95% CI 1.40–2.01), preoperative PSA level (aOR 1.02, 95% CI 1.01–1.03), as well as Hispanic ethnicity, Black race, and increasing D'Amico risk category, but not with age or comorbidity. Conclusion: We found a substantial rate of bone scan utilisation after RP. The majority were performed for PSA levels of <1 ng/mL where the likelihood of a positive test is low. More judicious use of imaging appears warranted in the post‐RP setting. [ABSTRACT FROM AUTHOR]

Objectives To assess bone‐density testing (BDT) use amongst prostate cancer survivors receiving androgen‐deprivation therapy (ADT), and downstream implications for osteoporosis and fracture diagnoses, as well as pharmacological osteoporosis treatment in a national integrated delivery system. Patients and methods We identified 17 017 men with prostate cancer who received any ADT between 2005 and 2014 using the Veterans Health Administration cancer registry and administrative data. We identified claims for BDT within a 3‐year period of ADT initiation. We then used multivariable regression to examine the association between BDT use and incident osteoporosis, fracture, and use of pharmacological treatment. Results We found that a minority of patients received BDT (n = 2 502, 15%); however, the rate of testing increased to >20% by the end of the study period. Men receiving BDT were older at diagnosis and had higher‐risk prostate cancer (both P < 0.001). Osteoporosis and fracture diagnoses, use of vitamin D ± calcium, and bisphosphonates were all more common in men who received BDT. After adjustment, BDT, and to a lesser degree ≥2 years of ADT, were both independently associated with incident osteoporosis, fracture, and osteoporosis treatment. Conclusions BDT is rare amongst patients with prostate cancer treated with ADT in this integrated delivery system. However, BDT was associated with substantially increased treatment of osteoporosis indicating an underappreciated burden of osteoporosis amongst prostate cancer survivors initiating ADT. Optimising BDT use and osteoporosis management in this at‐risk population appears warranted. [ABSTRACT FROM AUTHOR]

We sought to analyze utilization and survival outcomes of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (RCC) before and after introduction of targeted therapy. We identified patients with metastatic RCC between 1993 and 2010 in the SEER registry and examined temporal trends in utilization. We performed a joinpoint regression to determine when changes in utilization of CN occurred. We fitted multivariable proportional hazard models in full and propensity score-matched cohorts. We performed a difference-in-difference analysis to compare survival outcomes before and after introduction of targeted therapy. The proportion of patients undergoing CN increased from 1993 to 2004, from 29% to 39%. We identified a primary joinpoint of 2004, just prior to the introduction of targeted therapy. Beginning in 2005, there was a modest decrease in utilization of CN. CN was associated with a lower adjusted relative hazard (0.41, 95% confidence interval 0.34-0.43). Median survival among patients receiving CN increased in the targeted therapy era (19 vs. 13 months), while median survival among patients not receiving CN increased only slightly (4 vs. 3 months). Difference-in-difference analysis showed a significant decrease in hazard of death among patients who received CN in the targeted therapy era. Despite decreased utilization in the targeted therapy era, CN remains associated with improved survival. Prospective randomized trials are needed to confirm the benefit of CN among patients with metastatic RCC treated with novel targeted therapies. [ABSTRACT FROM AUTHOR]

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b OBJECTIVE To prospectively determine the accuracy of 14-, 18- and 20-G core needle biopsies to render the appropriate histological diagnosis of solid, enhancing renal masses, using a controlled, ex-vivo biopsy technique. PATIENTS AND METHODS From March 2007 to September 2007, 31 patients undergoing partial or radical nephrectomy were randomly selected for biopsy. After extirpative surgery, three ex-vivo biopsies were taken from each lesion with 14-, 18- and 20-G biopsy needles. One experienced genitourinary pathologist, unaware of patient identifiers and final pathology results, determined the biopsy histology and tumour grade, based on standard haematoxylin and eosin (H&E) techniques and immunohistochemistry. RESULTS The final pathological evaluation classified 21 masses (68%) as clear cell renal cell carcinoma (RCC), three (10%) as papillary RCC, three (10%) as chromophobe RCC, three (10%) as oncocytoma and one (3%) as a benign lymphoid infiltrate. The biopsy histology correlated with the final pathology in 29/31 cases (94%) with the 14-G, 30/31 cases (97%) with the 18-G and 25/31 cases (81%) with the 20-G needles. In two cases chromophobe RCC was misdiagnosed with oncocytoma, and vice versa. CONCLUSION In this study a minimum of an 18-G biopsy needle was the most accurate in determining the histological diagnosis. Clear cell and papillary RCCs were accurately diagnosed on biopsy using an 18-G, whereas oncocytoma and chromophobe RCC were difficult to differentiate using standard H&E techniques and immunohistochemistry. [ABSTRACT FROM AUTHOR]

Background: The mammalian target of rapamycin (mTOR) pathway is up-regulated in many human cancers, and agents targeting the mTOR pathway are in various stages of clinical development. The goal of the study was to evaluate the potential and limitations of targeting the mTOR pathway in renal cell carcinoma (RCC).Methods: Immunohistochemical analysis using antibodies against pAkt, PTEN, p27, and pS6 was performed on a tissue microarray constructed from paraffin-embedded specimens from 375 patients treated by nephrectomy for RCC. The expression was associated with pathological parameters and survival.Results: The mTOR pathway was more significantly altered in clear-cell RCC, high-grade tumors, and tumors with poor prognostic features. PS6 and PTEN showed the strongest associations with pathological parameters. Survival tree analysis regarding expression of cytoplasmic pAkt, nuclear pAkt, PTEN, cytoplasmic p27, and pS6 identified staining percentages of 40%, 10%, 75%, 7%, and 70%, respectively, as ideal cutoff values for stratification, with corresponding P-values of .03, .001, .02, .005, and <.0001, respectively. Interestingly, high nuclear pAkt expression was associated with a favorable prognosis, whereas high cytoplasmic pAkt expression was associated with a poor prognosis. In multivariate Cox regression analysis, ECOG PS, T classification, N classification, M classification, cytoplasmic Akt, nuclear pAkt, PTEN, and pS6 were independent prognostic factors of DSS.Conclusions: Components of the mTOR pathway are significantly associated with pathological features and survival. Not all RCC tumor types seem to be equally amenable to mTOR targeted therapy. PTEN, pAkt, p27, and pS6 may serve as surrogate parameters for patient selection and predicting prognosis. Patients with a highly activated mTOR pathway should benefit most from this therapy. External validation of our results is recommended. [ABSTRACT FROM AUTHOR]

The article presents medical research into the role of human molecular gene/protein expression markers in the staging and prognosis of renal cell carcinoma (RCC). An example of a molecular marker is carbonic anhydrase IX (CAIX). Future directions in molecular staging include predicting the response to targeted treatments and predicting the response to immunotherapy.

OBJECTIVE To define the prognostic relevance of capsular involvement (invasion with no penetration) and collecting-system invasion in patients with stage I (pT1N0M0) and stage II (pT2N0M0) renal cell carcinoma (RCC), by evaluating the outcome of patients treated with nephrectomy. PATIENTS AND METHODS In all, 519 patients from a kidney cancer database treated with nephrectomy for stage I and II RCC between 1985 and 2005 were assessed retrospectively. The primary endpoint was recurrence-free survival time. The prognostic relevance of capsular involvement and collecting-system invasion were examined using univariate and multivariate survival analysis. RESULTS Capsular involvement and collecting-system invasion were evident in 112 (21.6%) and 39 (7.5%) patients, respectively. Capsular involvement was associated with higher Fuhrman grades and larger tumours. The incidence of collecting-system invasion was higher in patients with microvascular invasion. The median follow-up was 49 months. In univariate analysis, patients with capsular involvement and collecting-system invasion had a worse prognosis than patients without ( P = 0.007 and <0.001, respectively). In multivariate analysis, capsular involvement (hazard ratio 1.84, P = 0.036) and collecting-system invasion (3.78, P < 0.001) were independent prognostic factors of recurrence-free survival. Interestingly, there was no survival difference between patients with capsular involvement in stage I/II and patients with invasion of perinephric tissue (pT3aN0M0). CONCLUSIONS These findings suggest that capsular involvement and collecting-system invasion are poor prognostic findings in stage I and II RCC. They should both be considered when planning the follow-up. A revised pT3a stage including patients with capsular involvement could improve its prognostic validity. [ABSTRACT FROM AUTHOR]

Reports on the open surgical management of renal cell carcinoma in the era of minimally invasive kidney surgery. Evidence showing that nephron-sparing surgery (NSS) for patients with small tumors is equivalent to total radical nephroctomy in terms of long-term survival; Safety and efficacy of NSS; Clinical factors determining prognosis and survival in the management of the disease.

Reports on the adjuvant therapy of renal cell carcinoma in patient selection and therapeutic options. Renal cell carcinoma, survival and prognostic factors; Postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma; Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma; Correlations with tumor oxygen measurements and prognostic in locally advanced carcinoma of the cervix.

The use of carbonic anhydrase IX as a promising molecular marker in RCC is described by authors from Los Angeles, who discuss the promise that molecular markers hold to improve diagnosis, staging, treatment surveillance and survival of patients with RCC. There is a whole range of new treatments being introduced in the management of metastatic renal cancer. The use of VEOF-targeted therapy has particular importance, especially as it has a strong genetically linked rationale for its potential success in this area. Authors from the USA show that substantial clinical activity has been reported in initial clinical trials. In prostate cancer, drugs targeting microtubules, such as taxanes, have already been introduced clinically, and their success has received widespread attention. A new group of drugs, the epothilones, have similar but not identical binding properties to microtubules, and authors from the USA describe how they have shown activity in hormone-refractory prostate cancer, and are moving to phase III testing. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The Oncotype DX Genomic Prostate Score (ODX‐GPS) is a gene expression assay that predicts disease aggressiveness. The objective of this study was to identify sociodemographic and regional factors associated with ODX‐GPS uptake.Data from Surveillance Epidemiology and End Results registries on men with localized prostate cancer with a Gleason score of 3 + 3 or 3 + 4, PSA ≤20 ng/mL, and stage T1c to T2c disease from 2013 through 2017 were linked with ODX‐GPS data. Census‐tract level neighborhood socioeconomic status (nSES) quintiles were constructed using a composite socioeconomic score. Multivariable logistic regression was used to estimate the associations of ODX‐GPS uptake with age at diagnosis, race and ethnicity, nSES, geographic region, insurance type, and marital status, accounting for National Comprehensive Cancer Network risk group, year of diagnosis, and clustering by census tract.Among 111,434 eligible men, 5.5% had ODX‐GPS test uptake. Of these, 78.3% were non‐Hispanic White, 9.6% were Black, 6.7% were Hispanic, and 3.6% were Asian American. Black men had the lowest odds of ODX‐GPS uptake (odds ratio, 0.70; 95% confidence interval [CI], 0.63–0.76). Those in the highest versus lowest quintile of nSES were 1.64 times more likely (95% CI, 1.38–2.94) to have ODX‐GPS uptake. The odds of ODX‐GPS uptake were statistically significantly higher among men residing in the Northeast, West, and Midwest compared to the South.Disparities in ODX‐GPS uptake by race, ethnicity, nSES, and geographical region were identified. Concerted efforts should be made to ensure that this clinical test is equitably available. [ABSTRACT FROM AUTHOR]