Functional Outcomes After Localized Prostate Cancer Treatment.

Importance: Adverse outcomes associated with treatments for localized prostate cancer remain unclear. Objective: To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer. Design, Setting, and Participants: An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. Exposures: Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease. Main Outcomes and Measures: Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function. Results: A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy. Conclusions and Relevance: Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. METHODS: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. RESULTS: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. CONCLUSIONS: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Estimating the Impact of the Inflation Reduction Act on the Out-of-Pocket Costs for Medicare Beneficiaries With Advanced Prostate Cancer.

INTRODUCTION: Combination systemic therapy for advanced prostate cancer has reduced mortality, but high out-of-pocket costs impose financial barriers for patients. The Inflation Reduction Act's $2,000 out-of-pocket spending cap for Medicare's prescription drug benefit (Part D) can potentially lower out-of-pocket spending for beneficiaries starting in 2025. This study aims to compare out-of-pocket spending for commonly prescribed regimens for advanced prostate cancer before and after implementation of the Inflation Reduction Act. METHODS: Medication regimens constructed to treat metastatic, hormone-sensitive prostate cancer consisted of baseline androgen deprivation therapy with traditional chemotherapy, androgen receptor inhibitors, and androgen biosynthesis inhibitors. Using 2023 Medicare Part B prices and the Medicare Part D plan finder, we estimated annual out-of-pocket costs under current law and under the Inflation Reduction Act's redesigned standard Part D benefit. RESULTS: Under current law, out-of-pocket costs for Part D drugs ranged from $464 to $11,336 per year. Under the Inflation Reduction Act, annual out-of-pocket costs for 2 regimens remained unchanged: androgen deprivation therapy with docetaxel and androgen deprivation therapy with abiraterone and prednisone. However, out-of-pocket costs for regimens using branded novel hormonal therapy were significantly lower under the 2025 law with potential savings estimated to be $9,336 (79.2%) for apalutamide, $9,036 (78.7%) for enzalutamide, and $8,480 (76.5%) for docetaxel and darolutamide. CONCLUSIONS: The $2,000 spending cap introduced by the Inflation Reduction Act may significantly decrease out-of-pocket costs and reduce financial toxicity associated with advanced prostate cancer treatment, impacting an estimated 25,000 Medicare beneficiaries.

Projected Savings for Generic Oncology Drugs Purchased via Mark Cuban Cost Plus Drug Company Versus in Medicare.

PURPOSE: Self-administered oncology drugs contribute disproportionately to Medicare Part D spending; prices often remain high even after generic entry. Outlets for low-cost drugs such as Mark Cuban Cost Plus Drug Company (MCCPDC) offer opportunities for decreased Medicare, Part D, and beneficiary spending. We estimate potential savings if Part D plans obtained prices such as those offered under the MCCPDC for seven generic oncology drugs. METHODS: Using the 2020 Medicare Part D Spending dashboard, Q3-2022 Part D formulary prices, and Q3-2022 MCCPDC prices for seven self-administered generic oncology drugs, we estimated Medicare savings by replacing Q3-2022 Part D unit costs with costs under the MCCPDC plan. RESULTS: We estimate potential savings of $661.8 million (M) US dollars (USD; 78.8%) for the seven oncology drugs studied. Total savings ranged from $228.1M USD (56.1%) to $2,154.5M USD (92.4%) compared with 25th and 75th percentiles of Part D plan unit prices. The median savings replacing Part D plan prices were abiraterone $338.0M USD, anastrozole $1.2M USD, imatinib 100 mg $15.6M USD, imatinib 400 mg $212.0M USD, letrozole $1.9M USD, methotrexate $26.7M USD, raloxifene $63.8M USD, and tamoxifen $2.6M USD. All 30-day prescription drug prices offered by MCCPDC generated cost savings except for three drugs offered at the 25th percentile Part D formulary pricing: anastrozole, letrozole, and tamoxifen. CONCLUSION: Replacing current Part D median formulary prices with MCCPDC pricing could yield significant savings for seven generic oncology drugs. Individual beneficiaries could save nearly $25,200 USD per year for abiraterone or between $17,500 USD and $20,500 USD for imatinib. Notably, Part D cash-pay prices for abiraterone and imatinib under the catastrophic phase of coverage were still more expensive than baseline MCCPDC prices.

The Impact of Medicare Low-income Subsidy on Access to Treatment, Treatment Choice, and Oncologic Outcomes in Patients With Metastatic Prostate Cancer.

PURPOSE: Patients eligible for Medicare Part D low-income subsidy have lower cost-sharing for both IV and oral cancer therapies. We evaluated associations between low-income subsidy and treatment choice, treatment initiation, and overall survival in patients with metastatic prostate cancer. MATERIALS AND METHODS: We identified men aged 66 years and older diagnosed with stage IV prostate cancer between 2010 and 2017 included in the Surveillance, Epidemiology, and End Results-Medicare linked data set. Using linear probability models, we evaluated the impact of low-income subsidy on type of first supplementary treatment (oral vs IV) among patients who received nonandrogen deprivation therapy supplementary systemic therapy, and initiation of any nonandrogen deprivation therapy supplementary systemic therapy. Overall survival was estimated with Kaplan-Meier curves. RESULTS: Of the 5,929 patients included, 1,766 (30%) had low-income subsidy. On multivariable analysis, those with low-income subsidy were more likely to receive oral as opposed to IV treatments compared to patients without low-income subsidy (probability difference: 17%, 95% CI 12, 22). However, patients with low-income subsidy were less likely to initiate any nonandrogen deprivation therapy supplementary systemic therapy (oral or IV) compared to those without low-income subsidy (probability difference: 7.9%, 95% CI 4.8-11). Additionally, patients with low-income subsidy experienced worse overall survival than those without low-income subsidy (P < .001). CONCLUSIONS: While low-income subsidy was associated with increased use of more expensive oral therapies in men with metastatic prostate cancer, barriers to accessing these treatments still exist. These findings stress the importance of continued efforts to improve health care access to low-income individuals.

The lived experience of prostate cancer: 10-year survivor perspectives following contemporary treatment of localized prostate cancer.

PURPOSE: Studies relying on standardized instruments to measure patient-centered harms and benefits of cancer treatment may fail to capture important elements of the lived experience of cancer patients. Further, qualitative studies on the survivorship experience of men with localized prostate cancer (PCa) are limited. We sought to explore the early experience, long-term experience, and advice provided for others among long-term survivors of localized PCa. METHODS: Semi-structured qualitative interviews with a subset (n = 66) of respondents to a survey of 10-year PCa survivors who underwent active surveillance, radical prostatectomy, or radiotherapy. Topics included early and long-term experiences and advice to other men and physicians. RESULTS: Immediately after treatment, men were mostly satisfied with radiation and active surveillance due to remaining whole and avoiding surgical removal of the prostate. Meanwhile, men treated with surgery felt relieved by the removal of cancer. Some early negative perception was related to short-term anxiety, particularly among men who underwent active surveillance. Long-term experiences included accepting the trade-offs of urinary and sexual side effects with survival. Most men fared well financially, some had strengthened relationships, and many reported greater appreciation and compassion. Men provided essential advice to other men and physicians on the importance of gathering detailed information on treatments and establishing a strong relationship with physicians. CONCLUSIONS: Long-term survivors of localized PCa generally do well by accepting the long-term effects of contemporary treatments, experiencing strengthened relationships, and developing a better overall life approach. IMPLICATIONS FOR CANCER SURVIVORS: We provide useful perspectives and insights for men opting to use current-day treatments for localized PCa.

Use of Active Surveillance vs Definitive Treatment Among Men With Low- and Favorable Intermediate-Risk Prostate Cancer in the US Between 2010 and 2018.

This cross-sectional study of data from the Surveillance, Epidemiology and End Results database assesses temporal trends in the use of active surveillance and watchful waiting vs definitive treatment in men with low- and favorable intermediate­risk prostate cancer in the US between 2010 and 2018.

Diagnostic Imaging in the Evaluation of Asymptomatic Microhematuria: Systematic Review and Meta-analysis.

PURPOSE: Microhematuria is a highly prevalent condition with a low associated risk of urothelial and upper tract malignancy. The AUA Guidelines recently changed recommendations for imaging favoring renal ultrasound for low- and intermediate-risk patients with microhematuria. We summarize the diagnostic test characteristics of computed tomography urography, renal ultrasound, and magnetic resonance urography in comparison with surgical pathology for the diagnosis of upper urinary tract cancer in microhematuria and gross hematuria patients. MATERIALS AND METHODS: This study is a systematic review and meta-analysis using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from evidence collected for the 2020 AUA Microhematuria Guidelines report, including studies assessing imaging following diagnosis of hematuria published from January 2010 through December 2019. RESULTS: The search identified 20 studies which reported the prevalence of malignant and benign diagnoses in relation to imaging modality, of which 6 were included in the quantitative analysis. For the detection of renal cell carcinoma and upper urinary tract carcinoma in patients with microhematuria and gross hematuria, computed tomography urography had a sensitivity of 94% (95% CI, 84%-98%) and a specificity of 99% (95%CI, 97%-100%) with a certainty of evidence rating of very low and low, respectively when 4 studies were pooled. In comparison, ultrasound demonstrated a sensitivity ranging from 14%-96% (low certainty of evidence) and a specificity of 99%-100% in 2 studies (moderate certainty of evidence), while magnetic resonance urography demonstrated a sensitivity of 83% and specificity of 86% in 1 study with a low certainty of evidence. CONCLUSIONS: In a limited data set for each individual imaging modality, computed tomography urography appears the most sensitive imaging modality for the diagnostic evaluation of microhematuria. Future studies will be needed to evaluate the clinical and health system financial impacts of the change in guideline recommendations from computed tomography urography to renal ultrasound in evaluating low- and intermediate-risk patients with microhematuria.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

PURPOSE: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. MATERIALS AND METHODS: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. RESULTS: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). CONCLUSIONS: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Association between body mass index and localized prostate cancer management and disease-specific quality of life.

Purpose: The purpose of this work is to describe the association between body mass index (BMI) and (1) management option for localized prostate cancer (PCa) and (2) disease-specific quality of life (ds-QoL) after treatment or active surveillance. Subjects/patients and methods: We analysed data from men with localized PCa managed with radical prostatectomy (RP), radiation therapy (RT), or active surveillance (AS) in a prospective, population-based cohort study. We evaluated the association between BMI and management option with multivariable multinomial logistic regression analysis. The association between BMI and ds-QoL was assessed using multivariable longitudinal linear regression. Regression models were adjusted for baseline domain scores, demographics, and clinicopathologic characteristics. Results: A total of 2378 men were included (medians [quartiles]: age 64 [59-69] years; BMI 27 kg/m2; 77% were non-Hispanic white); 29% were obese (BMI ≥ 30). Accounting for demographic and clinicopathologic features, BMI ≥ 28 kg/m2 was inversely associated with the likelihood of receiving RP (compared with RT) and became statistically significant at BMI ≥ 33 kg/m2 (maximum adjusted relative risk ratio = 0.80, 95% CI 0.67 to 0.95, p = 0.013 for BMI ≥ 33 vs. 25). Conversely, BMI was not significantly associated with the likelihood of receiving AS compared with RT. After stratification by management option, obese men who underwent definitive treatment were not found to have clinically worse ds-QoL. Obese men initially on AS appeared to have worse urinary incontinence than nonobese men, but this was not significant on an as-treated sensitivity analysis. Conclusions: Among men with localized PCa, those with BMI ≥ 33 kg/m2 were less likely to receive surgery than radiation. Obesity was not associated with ds-QoL in men undergoing definitive treatment, nor in men who remained on AS.

Implementation of a comprehensive prehabilitation program for patients undergoing radical cystectomy.

BACKGROUND: Coordinated preoperative optimization programs for radical cystectomy (RC) are limited and non-comprehensive. We evaluated the feasibility and acceptability of a coordinated, multi-faceted prehabilitation program for RC patients at a high-volume bladder cancer referral center. METHODS: We performed a narrative literature review for prehabilitation in bladder cancer management as of December 1, 2020, with specific emphasis on examining higher-level evidence sources. We selected domains with the highest level of evidence and recruited a multidisciplinary team of experts to design our program. We implemented a comprehensive prehabilitation program with a pre-defined order set as standard of care for all patients undergoing RC beginning February 1, 2021. Demographic and clinicopathologic data were collected prospectively. Rates of adherence to the prehabilitation program services were analyzed using Stata version 13. RESULTS: A total of 82 patients were enrolled between February - December 2021, of which 67 (81%) had undergone RC at data cutoff. Mean age was 68 years (SD 11) and 63 (76%) identified as male. Neoadjuvant chemotherapy (NAC) was utilized in 48 (59%) patients. The mean Charlson Comorbidity Index was 3.8 (SD 2.3). 100% of patients were screened for malnutrition, with 82% consuming nutritional supplements. Fifty-two percent of patients attended physical therapy pre-op. The 30-day and 30- to 90-day rates of complications were 56% and 40%, respectively. Resource length of stay (RLOS) declined after implementation of prehabilitation. CONCLUSIONS: Implementation of a comprehensive prehabilitation program at a high-volume bladder cancer referral center is feasible and has a modest effect on resource consumption and complications in our early experience.

Intensity of observation with active surveillance or watchful waiting in men with prostate cancer in the United States.

BACKGROUND: Population-based studies assessing various active surveillance (AS) protocols for prostate cancer, to date, have inferred AS participation by the lack of definitive treatment and use of post-diagnostic testing. This is problematic as evidence suggests that most men do not adhere to AS protocols. We sought to develop a novel method of identifying men on AS or watchful waiting (WW) independent of post-diagnostic testing and aimed to identify possible predictors of follow-up intensity in men on AS/WW. METHODS: A predictive model was developed using SEER watchful waiting data to identify men ≥66 years on AS between 2010-2015, irrespective of post-diagnostic testing, and applied to SEER-Medicare database. AS intensity among different variables including age, prostate-specific antigen (PSA) level, number of total and positive biopsy cores, Charlson comorbidity index, race (Black vs. non-Black), US census region, and county poverty, income, and education levels were compared using multivariable regression analyses for PSA testing, surveillance biopsy, and magnetic resonance imaging (MRI). RESULTS: A total of 2238 men were identified as being on AS. Of which, 81%, 33%, and 10% had a PSA test, surveillance biopsy, and MRI scan within 1-2 years, respectively. On multivariable analyses, Black men were less likely to have a PSA test (adjusted rate ratio [ARR] 0.60, 95% CI: 0.53-0.69), MRI scan (ARR 0.40, 95% CI: 0.24-0.68), and surveillance biopsy (ARR 0.71, 95% CI: 0.55-0.92) than non-Black men. Men within the highest income quintile were more likely to undergo PSA test (ARR 1.16, 95% CI: 1.05-1.27) and MRI scan (ARR 1.60, 95% CI 1.15-2.27) compared to men with the lowest income. CONCLUSIONS: Black men and men with lower incomes on AS underwent less rigorous monitoring. Further study is needed to understand and ameliorate differences in AS rigor stemming from sociodemographic differences.

Prostate volume, baseline urinary function, and their association with treatment choice and post-treatment urinary function in men treated for localized prostate cancer.

BACKGROUND: Benign prostatic hyperplasia, lower urinary tract symptoms, and prostate cancer often co-occur. Their effect on urinary function is an important consideration regarding prostate cancer treatment choices. While prostate volume (PV) and urinary symptoms are commonly used in treatment choice decision making, their association with post-treatment urinary function is unknown. We evaluated the associations between PV and baseline urinary function with treatment choice and post-treatment urinary function among men with localized prostate cancer. METHODS: We identified 1647 patients from CEASAR, a multicenter population-based, prospective cohort study of men with localized prostate cancer, for analysis. Primary outcomes were treatment choice and health-related quality of life (HRQOL) assessed by the 26-item Expanded Prostate Index Composite (EPIC-26) at pre-specified intervals up to 5 years. Multivariable analysis was performed, controlling for demographic and clinicopathologic features. RESULTS: Median baseline PV was 36 mL (IQR 27-48), and baseline urinary irritative/obstructive domain score was 87 (IQR 75-100). There was no observed clinically meaningful association between PV and treatment choice or post-treatment urinary function. Among patients with poor baseline urinary function, treatment with radiation or surgery was associated with statistically and clinically significant improvement in urinary function at 6 months which was durable through 5 years (improvement from baseline at 5 years: radiation 20.4 points, surgery 24.5 points). CONCLUSIONS: PV was not found to be associated with treatment modality or post-treatment urinary irritative/obstructive function among men treated for localized prostate cancer. Men with poor baseline urinary irritative/obstructive function improve after treatment with surgery or radiation therapy.

Association between adherence to radiation therapy quality metrics and patient reported outcomes in prostate cancer.

BACKGROUND: Prior studies have shown significant variability in the quality of prostate cancer care in the US with questionable associations between quality measures and patient reported outcomes. We evaluated the impact of compliance with nationally recognized radiation therapy (RT) quality measures on patient-reported health-related quality of life (HRQOL) outcomes in the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) cohort. METHODS: CEASAR is a population-based, prospective cohort study of men with localized prostate cancer from which we identified 649 who received primary RT and completed HRQOL surveys for inclusion. Eight quality measures were identified based on national guidelines. We analyzed the impact of compliance with these measures on HRQOL assessed by the 26-item Expanded Prostate Index Composite at pre-specified intervals up to 5 years after treatment. Multivariable analysis was performed controlling for demographic and clinicopathologic features. RESULTS: Among eligible participants, 566 (87%) patients received external beam radiation therapy and 83 (13%) received brachytherapy. Median age was 69 years (interquartile range: 64-73), 33% had low-, 43% intermediate-, and 23% high-risk disease. 28% received care non-compliant with at least one measure. In multivariable analyses, while some statistically significant associations were identified, there were no clinically significant associations between compliance with evaluated RT quality measures and patient reported urinary irritative, urinary incontinence, bowel, sexual or hormonal function. CONCLUSIONS: Compliance with RT quality measures was not meaningfully associated with patient-reported outcomes after prostate cancer treatment. Further work is needed to identify patient-centered quality measures of prostate cancer care.

Label-Free Enhancement of Adrenal Gland Visualization Using Near-Infrared Autofluorescence for Surgical Guidance.

BACKGROUND: During adrenalectomy, surgeons have traditionally relied on their subjective visual skills to distinguish adrenal glands (AGs) from retroperitoneal fat and surrounding structures, while ultrasound and exogenous contrast agents have been employed for intraoperative AG visualization, all of which have their limitations. We present a novel label-free approach that uses near-infrared autofluorescence (NIRAF) detection, which demonstrates potential for enhanced intraoperative AG visualization and efficient tumor resection during adrenalectomies. METHODS: Patients undergoing adrenalectomy or nephrectomy were enrolled for this feasibility study. NIRAF emitted beyond 800 nm was detected in vivo from AGs and surrounding tissues during open adrenalectomies or nephrectomies. NIRAF was also measured ex vivo in excised AGs following robotic adrenalectomies. NIRAF images of tissues were captured using near-infrared (NIR) camera systems, whereas NIRAF intensities were recorded concurrently using fiber-optic probe-based NIR devices. Normalized NIRAF intensities (expressed as mean ± standard error) were analyzed and compared. RESULTS: Among the 55 enrolled patients, NIRAF intensity was elevated significantly for AGs versus retroperitoneal fat and other structures. NIR images of AGs also revealed a distinct demarcation of NIRAF between adrenal cortex and other periadrenal structures. NIRAF intensity in AGs was decreased markedly in malignant adrenal tumors, while benign adrenal cortical tumors and healthy adrenal cortex exhibited the strongest NIRAF levels. CONCLUSIONS: Our preliminary findings indicate that NIRAF detection could be a promising label-free technology to enhance intraoperative AG visualization and holds immense potential for effective tumor demarcation during cortical-sparing adrenalectomies or adrenal-conserving surgeries.

Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease.

Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1+ASPN+FAP+ENG+) along with fewer T cells, elevated T cell dysfunction, and increased C1QB+TREM2+APOE+-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.