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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. The molecular and cellular underpinnings of cribriform prostate cancer aggressiveness remain to be explored. Here, the authors perform single-cell RNA-sequencing, TCR sequencing and histology and reveal cancer cell intrinsic pathways and an immunosuppressive tumour microenvironment.

PurposeStudies 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.MethodsSemi-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.ResultsImmediately 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.ConclusionsLong-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 SurvivorsWe provide useful perspectives and insights for men opting to use current-day treatments for localized PCa.

Purpose Racial disparities are apparent in the management and outcomes for prostate cancer; however, disparities in compliance to quality measures for radiation therapy for prostate cancer have not been previously studied. Therefore, the goal of the study was to characterize disparities in the compliance rates with quality measures. Methods The comparative effectiveness analysis of radiation therapy and surgery study is a population-based, prospective cohort study that enrolled 3708 men with clinically localized prostate cancer from 2011 to 2012. Compliance with 5 radiation-specific quality measures endorsed by national consortia as of 2011 was assessed, and compliance was compared by race using logistic regression. Results Overall, 604 men received definitive external beam radiation therapy (EBRT) of which 20% were self-reported black, 74% non-Hispanic white, and 6% Hispanic. Less than two-thirds of black and Hispanic men received EBRT that was compliant with all available quality measures ( p  = 0.012). Compared to white men, black men were less likely to receive dose-escalated EBRT (95% vs. 87%, p  = 0.011) and less likely to avoid unnecessary pelvic radiation for low-risk disease (99% vs. 20%, p  < 0.001). Compared to white men, Hispanic men were less likely to undergo image guidance (87% vs. 71%, p  = 0.04). Black and Hispanic men were more likely to receive EBRT from low-quality providers than white men. Conclusions Addressing disparities in access to providers that meet quality guidelines, and improving adherence to evidence-based processes of care may decrease racial/ethnic disparities in prostate cancer outcomes.

BackgroundBenign 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.MethodsWe 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.ResultsMedian 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).ConclusionsPV 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.

ABSTRACT BACKGROUND Female gender and black race are associated with delayed diagnosis and inferior survival in patients with bladder cancer. OBJECTIVE We aimed to determine the association between gender, race, and evaluation of microscopic hematuria (an early sign of bladder cancer). DESIGN AND PARTICIPANTS This was a cohort study using a 5 % random sample of fee-for-service Medicare beneficiaries diagnosed with incident hematuria (International Classification of Diseases, Ninth Revision [ICD-9] code 599.7x) between January 2009 and June 2010 in a primary care setting. Beneficiaries with pre-existing explanatory diagnoses or genitourinary procedures were excluded. MAIN MEASURES The main endpoint was completeness of the hematuria evaluation in the 180 days after diagnosis. Evaluations were categorized as complete, incomplete, or absent based on receipt of relevant diagnostic procedures and imaging studies. KEY RESULTS In all, 9,211 beneficiaries met the study criteria. Hematuria evaluations were complete in 14 %, incomplete in 21 %, and absent in 65 % of subjects. Compared to males, females were less likely to have a procedure (26 vs. 12 %), imaging (41 vs. 30 %), and a complete evaluation (22 vs. 10 %) ( p  < 0.001 for each comparison). Receipt of a complete evaluation did not differ by race. Controlling for baseline characteristics, a complete evaluation was less likely in white women (OR, 0.40 [95 % CI, 0.35–0.46]) and black women (OR, 0.46 [95 % CI, 0.29–0.70]) compared to white men; no difference was found between black and white men. CONCLUSIONS Women are less likely than men to undergo a complete and timely hematuria evaluation, a finding likely relevant to women’s more advanced stage at bladder cancer diagnosis. System-level process improvement between providers of urologic and primary care in the evaluation of hematuria may benefit women harboring malignancy.

Background Established risk factors for prostate cancer have not translated to effective prevention or adjuvant care strategies. Several epidemiologic studies suggest greater body adiposity may be a modifiable risk factor for high-grade (Gleason 7, Gleason 8-10) prostate cancer and prostate cancer mortality. However, BMI only approximates body adiposity, and may be confounded by centralized fat deposition or lean body mass in older men. Our objective was to use bioelectric impedance analysis (BIA) to measure body composition and determine the association between prostate cancer and total body fat mass (FM) fat-free mass (FFM), and percent body fat (%BF), and which body composition measure mediated the association between BMI or waist circumference (WC) with prostate cancer. Methods The study used a multi-centered recruitment protocol targeting men scheduled for prostate biopsy. Men without prostate cancer at biopsy served as controls (n = 1057). Prostate cancer cases were classified as having Gleason 6 (n = 402), Gleason 7 (n = 272), or Gleason 8-10 (n = 135) cancer. BIA and body size measures were ascertained by trained staff prior to diagnosis, and clinical and comorbidity status were determined by chart review. Analyses utilized multivariable linear and logistic regression. Results Body size and composition measures were not significantly associated with low-grade (Gleason 6) prostate cancer. In contrast, BMI, WC, FM, and FFM were associated with an increased risk of Gleason 7 and Gleason 8-10 prostate cancer. Furthermore, BMI and WC were no longer associated with Gleason 8-10 (OR BMI = 1.039 (1.000, 1.081), OR WC = 1.016 (0.999, 1.033), continuous scales) with control for total body FFM (OR BMI = 0.998 (0.946, 1.052), OR WC = 0.995 (0.974, 1.017)). Furthermore, increasing FFM remained significantly associated with Gleason 7 (OR FFM = 1.030 (1.008, 1.052)) and Gleason 8-10 (OR FFM = 1.044 (1.014, 1.074)) after controlling for FM. Conclusions Our results suggest that associations between BMI and WC with high-grade prostate cancer are mediated through the measurement of total body FFM. It is unlikely that FFM causes prostate cancer, but instead provides a marker of testosterone or IGF1 activities involved with retaining lean mass as men age.

Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy. The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1–T4, N0–N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than −15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676. Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI −9·6% to 10·9%; pnon-inferiority=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group). In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types. National Institutes of Health National Cancer Institute.

Background Recognizing the limitations of prostate-specific antigen (PSA) screening and the morbidity of prostate biopsies, several blood- and urine-based biomarkers have been proposed for pre-biopsy risk stratification. These assays aim to reduce the frequency of unnecessary biopsies (i.e., negative or Grade Group 1 [GG1]) while maintaining highly sensitive detection of clinically significant cancer (GG ≥ 2) prostate cancer. Methods We reviewed the literature describing the use of currently available blood- and urine-based biomarkers for detection of GG ≥ 2 cancer, including the Prostate Health Index (PHI), 4Kscore, MyProstateScore (MPS), SelectMDx, ExoDx Prostate Intelliscore (EPI), and IsoPSA. To facilitate clinical application, we focused on the use of biomarkers as a post-PSA secondary test prior to biopsy, as proposed in clinical guidelines. Our outcomes included test performance measures—sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV)—as well as clinical outcomes resulting from biomarker use (i.e., unnecessary biopsies avoided, GG ≥ 2 cancers missed). Results Contemporary validation data (2015–2023) reveal that currently available biomarkers provide ~15–50% specificity at a sensitivity of 90–95% for GG ≥ 2 PCa. Clinically, this indicates that secondary use of biomarker testing in men with elevated PSA could allow for avoidance of up to 15–50% of unnecessary prostate biopsies, while preserving detection of 90–95% of GG ≥ 2 cancers that would be detected under the traditional “biopsy all” approach. Conclusions The contemporary literature further supports the proposed role of post-PSA biomarker testing to reduce the use of invasive biopsy while maintaining highly sensitive detection of GG ≥ 2 cancer. Questions remain regarding the optimal application of biomarkers in combination or in sequence with mpMRI.

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.

Cytoreductive nephrectomy following immune checkpoint blockade (ICB) in metastatic renal cell carcinoma remains controversial, with limited data on its clinical and pathological outcomes. This study evaluated the outcomes of patients undergoing deferred cytoreductive nephrectomy (dCN) after ICB-based treatment, focusing on the radiologic and pathological responses, and postoperative clinical outcomes. We retrospectively reviewed 24 patients with metastatic or locally advanced RCC who underwent dCN after ICB at a single institution between April 2018 and May 2024. We assessed the radiological response to ICB, pathological findings (presence and extent of necrosis) in resected primary tumors, and postoperative clinical outcomes, including the rate of patients without measurable disease and those who discontinued systemic therapy. Median ICB exposure prior to surgery was 11.3 months. Radiologically, 67% of patients had partial response, 29% had stable disease, and 4% had a complete response. Pathology showed 96% of specimens with necrosis, 21% of specimens showing no residual disease (pT0), and 21% exhibiting ≥95% necrosis. Postoperatively, 50% of patients had nonmeasurable disease of first follow-up scans, and 54% discontinued systemic therapy, with 9 patients remaining on surveillance at last follow-up. Limitations include the small sample size and retrospective design. Deferred CN following ICB therapy is feasible. Extensive necrosis in the resected surgical specimen after ICB-based therapy requires further investigation as a prognostic marker for durable responses off systemic therapy.