Patterns of multispecialty care for low- and intermediate-risk prostate cancer in the use of active surveillance.

BACKGROUND: Multidisciplinary models of care have been advocated for prostate cancer (PC) to promote shared decision-making and facilitate quality care. Yet, how this model applies to low-risk disease where the preferred management is expectant remains unclear. Accordingly, we examined recent practice patterns in specialty visits for low/intermediate-risk PC and resultant use of active surveillance (AS). METHODS: Using SEER-Medicare, we ascertained whether patients saw urology and radiation oncology (i.e., multispecialty care) versus urology alone, based on self-designated specialty codes, for newly diagnosed PC from 2010 to 2017. We also examined the association with AS, defined as the absence of treatment within 12 months of diagnosis. Time trends were analyzed using Cochran-Armitage test. Chi-squared and logistic regression analyses were applied to compare sociodemographic and clinicopathologic characteristics between these models of care. RESULTS: The proportion of patients seeing both specialists was 35.5% and 46.5% for low- and intermediate-risk patients respectively. Trend analysis showed a decline in multispecialty care in low-risk patients (44.1% to 25.3% years 2010-2017; P < 0.001). Between 2010 and 2017, the use of AS increased 40.9% to 68.6% (P < 0.001) and 13.1% to 24.6% (P < 0.001) for patients seeing urology and those seeing both specialists respectively. Age, urban residence, higher education, SEER region, co-morbidities, frailty, Gleason score, predicted receipt of multispecialty care (all P < 0.02). CONCLUSIONS: Uptake of AS among men with low-risk PC has occurred primarily under the purview of urologists. While selection is certainly at play, these data suggest that multispecialty care may not be required to promote the utilization of AS for men with low-risk PC.

Use of expectant management based on prostate cancer risk and health status: How far are we from a risk-adapted approach?

OBJECTIVES: While active surveillance, a form of expectant management (EM), is preferred for patients with low-risk prostate cancer (PCa), some favor a more risk-adapted approach that recognizes patient preferences and condition-specific factors. However, previous research has shown non-patient-related factors often drive PCa treatment. In this context, we characterized trends in AS with respect to disease risk and health status. METHODS AND MATERIALS: Using SEER-Medicare data, we identified men 66 years and older diagnosed with localized low- and intermediate-risk PCa from 2008 to 2017 and examined receipt of EM, defined as the absence of treatment (i.e., surgery, cryotherapy, radiation, chemotherapy, and androgen deprivation therapies) within 1 year of diagnosis. We performed bivariable analysis to compare trends in use for EM vs. treatment, stratified by disease risk (i.e., Gleason 3+3, 3+4, 4+3; PSA<10, 10-20) and health status (i.e., NCI Comorbidity Index (NCI), frailty, life expectancy). We then ran a multivariable logistic regression model to examine determinants of EM. RESULTS: Within this cohort, 26,364 (38%) were categorized as low-risk (i.e., Gleason 3+3 and PSA<10) and 43,520 (62%) as intermediate-risk (i.e., all others). Over the study period, use of EM significantly increased across all risk groups, except for Gleason 4+3 (P = 0.662), as well across all health status groups. However, linear trends did not differ significantly between frail vs. nonfrail patients for both those categorized as low-risk (P = 0.446) and intermediate-risk (P = 0.208). Trends also did not differ between NCI 0 vs. 1 vs. >1 for low-risk PCa (P = 0.395). In the multivariable models, EM was associated with increasing age and being frail for men with both low- and intermediate risk disease. Conversely, EM selection was negatively associated with higher comorbidity score. CONCLUSIONS: EM increased significantly over time for patients with low- and favorable intermediate-risk disease, with the most notable differences based on age and Gleason score. In contrast, trends in uptake of EM did not differ substantively by health status, suggesting that physicians may not be effectively incorporating patient health into PCa treatment decisions. Additional work is needed to develop interventions that recognize health status as an essential component of a risk-adapted approach.

Patterns and associations of smoking and electronic cigarette use among survivors of tobacco related and non-tobacco related cancers: A nationally representative cross-sectional analysis.

BACKGROUND: Tobacco-use among cancer survivors leads to preventable morbidity, mortality, and increased healthcare costs. We sought to explore the prevalence of smoking and e-cigarette use among survivors of tobacco and non-tobacco related cancers. METHODS: A cross-sectional analysis was conducted using the 2015-2018 National Health Interview Survey. Our primary outcome was the prevalence of current cigarette smoking or e-cigarette use among adults with self-reported history of tobacco related or non-tobacco related cancer. Logistic regression analysis was to assess the association of reported cancer type with cigarette smoking or e-cigarette use. Secondary outcomes included yearly trends and dual use. RESULTS: A total of 12,984 respondents reported a history of cancer, representing a weighted estimate of 5,060,059 individuals with a history of tobacco-related malignancy and 17,583,788 with a history of a tobacco and non-tobacco related cancer, respectively. Survivors of tobacco-related cancers had a significantly higher prevalence of current cigarette use (18.2 % vs 9.7 %, P < 0.0001), e-cigarette use (2.7 % vs 1.6 %, P < 0.0001) and similar rates of dual use. The prevalence of cigarette smoking among all survivors increased as time increased from the year of diagnosis up to 2 years post-diagnosis (P = 0.047). Odds of reporting current cigarette smoking use was higher for survivors of tobacco-related cancers, adjusted for sociodemographic factors (OR1.69, 95 % CI 1.44-1.99). CONCLUSIONS: Survivors of tobacco-related cancers have a higher prevalence of current cigarette smoking and e-cigarette use compared to survivors of non-tobacco related cancers. There was a sequential increase in the prevalence of cigarette use during each subsequent year from the time of a new cancer diagnosis, underscoring the need for long term tobacco cessation support among newly diagnosed adults with cancer.

Perceptions of e-cigarette harm among cancer survivors: Findings from a nationally representative survey.

BACKGROUND: The growth in e-cigarette use may be driven by the perception that they are a safer, healthier alternative to conventional cigarettes. However, their long-term health implications are not well known and use is discouraged by most cancer societies. It is currently unclear how cancer survivors perceive the risks associated with e-cigarette and how this may influence use in this population. METHODS: A cross-sectional analysis was conducted using the Health Information National Trends Survey (HINTS) (Years 2017-2019). Our primary study outcome was the perception of harm associated with e-cigarettes compared to traditional cigarettes among adults with and without a self-reported history of cancer. We used logistic regression analyses assessing the association of a cancer history with the perception that e-cigarettes are as much or more harmful than cigarettes. RESULTS: A total of 11,846 respondents (weighted population estimate 243,728,483) were included. Of these, 26.6% reported a history of cancer. The proportion of cancer survivors who perceived e-cigarettes to be as much or more harmful than conventional cigarettes was similar to non-cancer respondents (70.6% vs 68.3%, P = 0.35). There was no difference in perception of harm among cancer and non-cancer respondents, adjusted for sociodemographic factors (OR 0.82, 95% CI 0.6-1.1). Past (OR 9.06, 95% Cl 5.06-16.20) and never e-cigarette use (OR 23.40, 95% Cl 13.56-40.38) as well as having a history of cardiopulmonary disease (OR 1.28, 95% Cl 1.05-1.56) was associated with higher odds of perceiving e-cigarettes to be as much or more harmful. CONCLUSION: Cancer survivors commonly perceive e-cigarettes to be as much or more harmful than traditional cigarettes though these findings are similar to perceptions among adults without a history of cancer. There is a strong association with avoidance of e-cigarette products among those who perceive them to be harmful.

Patterns of Current Cigarette Smoking, Quit Attempts and Cessation Counseling among Survivors of Smoking-Related and Nonsmoking-Related Urological Malignancies: A Nationally Representative Cross-Sectional Analysis.

PURPOSE: Cigarette smoking is the leading modifiable risk factor for several genitourinary malignancies. Although smoking cessation after genitourinary cancer diagnosis is a critical component of survivorship, factors related to continued smoking are under studied. MATERIALS AND METHODS: A cross-sectional analysis was conducted using data from the National Health Interview Survey (2014-2018). Our primary study outcome was the prevalence and correlates of cigarette smoking among adults with a history of smoking-related (kidney or bladder) urological cancer compared to a nonsmoking-related control (prostate cancer). We used regression analyses to assess the association of having a smoking-related genitourinary cancer history with continued cigarette smoking after diagnosis. Secondary outcomes were yearly smoking trends, quit attempts and reported receipt of smoking cessation counseling. RESULTS: A total of 2,664 respondents reported a history of genitourinary cancer, representing weighted estimates of 990,820 (smoking-related genitourinary cancer) and 2,616,596 (prostate cancer) adults. Survivors of smoking-related genitourinary cancers had a significantly higher overall prevalence of current cigarette use (14.8% vs 8.6%, p <0.001) and also reported more frequent receipt of counseling (79.8% vs 66.2%, p=0.02) but did not attempt to quit any more often than those with prostate cancer (52.4% vs 47.2%, p=0.44). Time trends demonstrated stable and persistent cigarette use among survivors of all genitourinary cancers. After adjustment for sociodemographic confounders, cancer type was not associated with current cigarette smoking (OR 1.23, 95% CI 0.86-1.77). However, older age and more advanced educational attainment were associated with lower odds of current cigarette smoking, while single marital status was associated with higher odds. CONCLUSIONS: In this population-based cross-sectional study of survivors of genitourinary cancers, those with a reported smoking-related genitourinary cancer had a higher prevalence of current cigarette smoking compared to those with prostate cancer, our nonsmoking-related control. Those with smoking-related genitourinary cancers reported more frequent receipt of smoking cessation counseling.

Salvage Pelvic Lymph Node Dissection and Current State of Imaging for Recurrent Prostate Cancer: Does a Standard Exist?

PURPOSE OF REVIEW: We aim to evaluate the efficacy of salvage lymph node dissection (SLND) for nodal recurrent prostate cancer after primary treatment. We also provide a review of the diagnostic performance of next-generation sequencing (next-generation imaging (NGI)) radiotracers in the salvage setting. RECENT FINDINGS: Most studies evaluating SLND include a heterogeneous population with a small sample size and are retrospective in design. The 5-year clinical recurrence-free and cancer-specific survival following SLND are 26-52% and 57-89%, respectively, among prospective studies. NGI improves accuracy in detecting nodal recurrence compared to conventional CT, with PMSA PET-CT showing the most promise. However, limited studies exist comparing imaging modalities and performance is variable at low PSA values. SLND is a promising treatment option, but more prospective data are needed to determine the ideal surgical candidate and long-term oncologic outcomes. More studies comparing different NGI are needed to determine the best imaging modality in patients who may be candidates for salvage treatment.

National trends and disparities of minimally invasive surgery for localized renal cancer, 2010 to 2015.

PURPOSE: To investigate national utilization trends of minimally-invasive partial nephrectomy (PN) and minimally-invasive radical nephrectomy (RN), and to identify disparities in the usage of these techniques across different sociodemographic subgroups. MATERIALS AND METHODS: A retrospective cohort study was conducted using the National Cancer Database to identify patients undergoing partial or RN for cT1N0M0 renal cancer diagnosed between 2010 and 2015. Main outcomes of interest were the utilizations of minimally-invasive (robotic and laparoscopic) PN and RN. RESULTS: A total of 46,346 and 37,712 subjects who underwent PN and RN, respectively, were analyzed. During the study interval, increased utilization of robotic surgery paralleled the decreased utilization of open surgery. Robotic PN increased from 35.2% to 63.7% and robotic RN increased from 10.3% to 26.3%. The utilization of laparoscopic surgery was decreasing for PN but stable for RN through the study period. In the PN cohort, multivariable logistic regression showed non-Hispanic black (odds ratio [OR] = 0.90 [95% CI, 0.84-0.96]) and Hispanic (OR = 0.91 [0.84-0.99]) subjects were associated with less utilization of minimally invasive surgery (MIS) (vs. non-Hispanic white). Younger (18-64 years) Medicare (OR = 0.83 [0.77-0.90]), Medicaid (OR = 0.80 [0.74-0.87]), and uninsured (OR = 0.55 [0.49-0.62]) were also associated with less utilization of MIS (vs. private insurance). Compared with low socioeconomic status (SES), upper middle (OR = 1.14 [1.07-1.21]) and high (OR = 1.24 [1.16-1.33]) SES were associated with higher utilization of MIS. Similar demographic, insurance, and SES-related disparities were identified in the RN cohort. CONCLUSIONS: Utilization of MIS for localized renal cancer has increased significantly and was mainly attributed to increased usage of robotic surgery. Racial/ethnic, insurance, and SES related disparities in MIS utilization were identified. Our findings demonstrate a targetable subgroup of patients who do not have the same access to advances in surgical technology.

Mitochondrial alterations in PINK1 deficient cells are influenced by calcineurin-dependent dephosphorylation of dynamin-related protein 1.

PTEN-induced novel kinase 1 (PINK1) mutations are associated with autosomal recessive parkinsonism. Previous studies have shown that PINK1 influences both mitochondrial function and morphology although it is not clearly established which of these are primary events and which are secondary. Here, we describe a novel mechanism linking mitochondrial dysfunction and alterations in mitochondrial morphology related to PINK1. Cell lines were generated by stably transducing human dopaminergic M17 cells with lentiviral constructs that increased or knocked down PINK1. As in previous studies, PINK1 deficient cells have lower mitochondrial membrane potential and are more sensitive to the toxic effects of mitochondrial complex I inhibitors. We also show that wild-type PINK1, but not recessive mutant or kinase dead versions, protects against rotenone-induced mitochondrial fragmentation whereas PINK1 deficient cells show lower mitochondrial connectivity. Expression of dynamin-related protein 1 (Drp1) exaggerates PINK1 deficiency phenotypes and Drp1 RNAi rescues them. We also show that Drp1 is dephosphorylated in PINK1 deficient cells due to activation of the calcium-dependent phosphatase calcineurin. Accordingly, the calcineurin inhibitor FK506 blocks both Drp1 dephosphorylation and loss of mitochondrial integrity in PINK1 deficient cells but does not fully rescue mitochondrial membrane potential. We propose that alterations in mitochondrial connectivity in this system are secondary to functional effects on mitochondrial membrane potential.

The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial and apparently sporadic Parkinson disease. LRRK2 is a multidomain protein kinase with autophosphorylation activity. It has previously been shown that the kinase activity of LRRK2 is required for neuronal toxicity, suggesting that understanding the mechanism of kinase activation and regulation may be important for the development of specific kinase inhibitors for Parkinson disease treatment. Here, we show that LRRK2 predominantly exists as a dimer under native conditions, a state that appears to be stabilized by multiple domain-domain interactions. Furthermore, an intact C terminus, but not N terminus, is required for autophosphorylation activity. We identify two residues in the activation loop that contribute to the regulation of LRRK2 autophosphorylation. Finally, we demonstrate that LRRK2 undergoes intramolecular autophosphorylation. Together, these results provide insight into the mechanism and regulation of LRRK2 kinase activity.