Wireless electrostimulation for cancer treatment: An integrated nanoparticle/coaxial fiber mesh platform.

Cancer, namely breast and prostate cancers, is the leading cause of death in many developed countries. Controlled drug delivery systems are key for the development of new cancer treatment strategies, to improve the effectiveness of chemotherapy and tackle off-target effects. In here, we developed a biomaterials-based wireless electrostimulation system with the potential for controlled and on-demand release of anti-cancer drugs. The system is composed of curcumin-loaded poly(3,4-ethylenedioxythiophene) nanoparticles (CUR/PEDOT NPs), encapsulated inside coaxial poly(glycerol sebacate)/poly(caprolactone) (PGS/PCL) electrospun fibers. First, we show that the PGS/PCL nanofibers are biodegradable, which allows the delivery of NPs closer to the tumoral region, and have good mechanical properties, allowing the prolonged storage of the PEDOT NPs before their gradual release. Next, we demonstrate PEDOT/CUR nanoparticles can release CUR on-demand (65 % of release after applying a potential of -1.5 V for 180 s). Finally, a wireless electrostimulation platform using this NP/fiber system was set up to promote in vitro human prostate cancer cell death. We found a decrease of 67 % decrease in cancer cell viability. Overall, our results show the developed NP/fiber system has the potential to effectively deliver CUR in a highly controlled way to breast and prostate cancer in vitro models. We also show the potential of using wireless electrostimulation of drug-loaded NPs for cancer treatment, while using safe voltages for the human body. We believe our work is a stepping stone for the design and development of biomaterial-based future smarter and more effective delivery systems for anti-cancer therapy.

Evaluating appropriateness of 18F-fluciclovine PET/CT relative to standard of care imaging guidelines and the impact of ADT on positivity: a prospective study in 62 Veterans Administration patients at a single institution.

BACKGROUND: According to the National Comprehensive Cancer Network Guidelines, 18F-fluciclovine PET/CT is considered appropriate after negative standard of care (SOC) imaging. OBJECTIVE: To prospectively compare 18F-fluciclovine to SOC imaging, investigate whether it should be done when SOC imaging is (+), and evaluate its detection rate in patients receiving androgen deprivation therapy. METHODS: We recruited 57 prostate cancer patients with biochemical recurrence with 18F-fluciclovine PET/CT and SOC imaging within 30 days. Prostate-specific antigen (PSA) level, Gleason score (GS), history of radical prostatectomy (RP), radiation therapy (RT) or hormone therapy (HT) were reviewed. RESULTS: The 57 patients had a median PSA of 2.6 and average GS of 7.4; 27 (47.4%) had RP, 28 (49.1%) had RT, 1 (1.75%) had HT and 1 (1.75%) observation only. 18F-fluciclovine identified disease recurrence in 45/57 patients (78.9%), including oligometastasis in 18/45 (40%). SOC imaging identified recurrent disease in 12/57 patients (21.1%) while 18F-fluciclvoine identified additional sites of disease in 11/12 (91.7%). The (+) 18F-fluciclovine studies had a median PSA 2.6 ng/ml compared to 6.0 ng/ml in the (+) SOC studies. CONCLUSION: 18F-fluciclovine was superior to SOC imaging for lesion detection, identification of oligometastasis and identification of additional sites of disease.

68Ga-RM2 PET-MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial.

BACKGROUND: National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer. In this study, we aimed to evaluate the diagnostic performance of the GRPR-targeting radiopharmaceutical 68Ga-RM2 in patients with biochemical recurrence of prostate cancer. METHODS: This single-centre, single-arm, phase 2/3 trial was done at Stanford University (USA). Adult patients (aged ≥18 years) with biochemical recurrence of prostate cancer, a Karnofsky performance status of 50 or higher, increasing prostate-specific antigen concentration 0·2 ng/mL or more after prostatectomy or 2 ng/mL or more above nadir after radiotherapy, and non-contributory conventional imaging (negative CT or MRI, and bone scan) were eligible. All participants underwent 68Ga-RM2 PET-MRI. The primary outcome was the proportion of patients with PET-positive findings on 68Ga-RM2 PET-MRI compared with MRI alone after initial therapy, at a per-patient and per-lesion level. The primary outcome would be considered met if at least 30% of patients had one or more lesions detected by 68Ga-RM2 PET-MRI and the detection by 68Ga-RM2 PET-MRI was significantly greater than for MRI. Each PET scan was interpreted by three independent masked readers using a standardised evaluation criteria. This study is registered with ClinicalTrials.gov, NCT02624518, and is complete. FINDINGS: Between Dec 12, 2015, and July 27, 2021, 209 men were screened for eligibility, of whom 100 were included in analyses. Median follow-up was 49·3 months (IQR 36·7-59·2). The primary endpoint was met; 68Ga-RM2 PET-MRI was positive in 69 (69%) patients and MRI alone was positive in 40 (40%) patients (p<0·0001). In the per-lesion analysis 68Ga-RM2 PET-MRI showed significantly higher detection rates than MRI alone (143 vs 96 lesions; p<0·0001). No grade 1 or worse events were reported. INTERPRETATION: 68Ga-RM2 PET-MRI showed better diagnostic performance than MRI alone in patients with biochemical recurrence of prostate cancer. Further prospective comparative studies with PSMA-targeted PET are needed to gain a better understanding of GRPR and PSMA expression patterns in these patients. FUNDING: The US Department of Defense.

The Impact of Positron Emission Tomography Imaging and Tumor Molecular Profiling on Risk Stratification, Treatment Choice, and Oncological Outcomes of Patients with Primary or Relapsed Prostate Cancer: An International Collaborative Review of the Existing Literature.

CONTEXT: The clinical introduction of next-generation imaging methods and molecular biomarkers ("radiogenomics") has revolutionized the field of prostate cancer (PCa). While the clinical validity of these tests has thoroughly been vetted, their clinical utility remains a matter of investigation. OBJECTIVE: To systematically review the evidence to date on the impact of positron emission tomography (PET) imaging and tissue-based prognostic biomarkers, including Decipher, Prolaris, and Oncotype Dx, on the risk stratification, treatment choice, and oncological outcomes of men with newly diagnosed PCa or those with biochemical failure (BCF). EVIDENCE ACQUISITION: We performed a quantitative systematic review of the literature using the MEDLINE, EMBASE, and Web of Science databases (2010-2022) following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines. The validated Quality Assessment of Diagnostic Accuracy Studies 2 scoring system was used to assess the risk of bias. EVIDENCE SYNTHESIS: A total of 148 studies (130 on PET and 18 on biomarkers) were included. In the primary PCa setting, prostate-specific membrane antigen (PSMA) PET imaging was not useful in improving T staging, moderately useful in improving N staging, but consistently useful in improving M staging in patients with National Comprehensive Cancer Network (NCCN) unfavorable intermediate- to very-high-risk PCa. Its use led to a management change in 20-30% of patients. However, the effect of these treatment changes on survival outcomes was not clear. Similarly, biomarkers in the pretherapy primary PCa setting increased and decreased the risk, respectively, in 7-30% and 32-36% of NCCN low-risk and 31-65% and 4-15% of NCCN favorable intermediate-risk patients being considered for active surveillance. A change in management was noted in up to 65% of patients, with the change being in line with the molecular risk-based reclassification, but again, the impact of these changes on survival outcomes remained unclear. Notably, in the postsurgical primary PCa setting, biomarker-guided adjuvant radiation therapy (RT) was associated with improved oncological control: Δ↓ 2-yr BCF by 22% (level 2b). In the BCF setting, the data were more mature. PSMA PET was consistently useful in improving disease localization-Δ↑ detection for T, N, and M staging was 13-32%, 19-58%, and 9-29%, respectively. Between 29% and 73% of patients had a change in management. Most importantly, these management changes were associated with improved survival outcomes in three trials: Δ↑ 4-yr disease-free survival by 24.3%, Δ↑ 6-mo metastasis-free survival (MFS) by 46.7%, and Δ↑ androgen deprivation therapy-free survival by 8 mo in patients who received PET-concordant RT (level 1b-2b). Biomarker testing in these patients also appeared to be helpful in risk stratifying and guiding the use of early salvage RT (sRT) and concomitant hormonal therapy. Patients with high-genomic-risk scores benefitted from treatment intensification: Δ↑ 8-yr MFS by 20% with the use of early sRT and Δ↑ 12-yr MFS by 11.2% with the use of hormonal therapy alongside early sRT, while low-genomic-risk score patients did equally well with initial conservative management (level 3). CONCLUSIONS: Both PSMA PET imaging and tumor molecular profiling provide actionable information in the management of men with primary PCa and those with BCF. Emerging data suggest that radiogenomics-guided treatments translate into direct survival benefits for patients, however, additional prospective data are awaited. PATIENT SUMMARY: In this review, we evaluated the utility of prostate-specific membrane antigen positron emission tomography and tumor molecular profiling in guiding the care of men with prostate cancer (PCa). We found that these tests augmented risk stratification, altered management, and improved cancer control in men with a new diagnosis of PCa or for those experiencing a relapse.

Does Urologist-level Utilization of Active Surveillance for Low-risk Prostate Cancer Correspond with Utilization of Active Surveillance for Small Renal Masses?

Active surveillance (AS) for prostate cancer (CaP) or small renal masses (SRMs) helps in limiting the overtreatment of indolent malignancies. Implementation of AS for these conditions varies substantially across individual urologists. We examined the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry to assess for correlation of AS between patients with low-risk CaP and patients with SRM managed by individual urologists. We identified 27 urologists who treated at least ten patients with National Comprehensive Cancer Network low-risk CaP and ten patients with SRMs between 2017 and 2021. For surgeons in the lowest quartile of AS use for low-risk CaP (<74%), 21% of their patients with SRMs were managed with AS, in comparison to 74% of patients of surgeons in the highest quartile (>90%). There was a modest positive correlation between the surgeon-level risk-adjusted proportions of patients managed with AS for low-risk CaP and for SRMs (Pearson correlation coefficient 0.48). A surgeon's tendency to use AS to manage one low-risk malignancy corresponds to their use of AS for a second low-risk condition. By identifying and correcting structural issues associated with underutilization of AS, interventions aimed at increasing AS use may have effects that influence clinical tendencies across a variety of urologic conditions. PATIENT SUMMARY: The use of active surveillance (AS) for patients with low-risk prostate cancer or small kidney masses varies greatly among individual urologists. Urologists who use AS for low-risk prostate cancer were more likely to use AS for patients with small kidney masses, but there is room to improve the use of AS for both of these conditions.

Impact of the COVID-19 pandemic on delivery of prostate cancer care in Australia: An interrupted time series analysis.

The COVID-19 pandemic led to a major disruption to health services across the world. The aim of this population-based study was to assess the downstream effects of the pandemic on diagnostic tests and treatment activities related to prostate cancer (PC). The Australian Government Department of Health Medicare Benefits Schedule and the Pharmaceutical Benefits Scheme databases were queried from January 2010 to June 2022. Two interrupted time series were performed Pre-COVID (January 2010 to February 2020) and peri-COVID (March 2020 to June 2022). Temporal modeling was performed to account for seasonal variation. Pre-COVID-19, monthly prostate-specific antigen (PSA) testing showed a declining trend and testing decreased by 81 tests per 100 000 annually. A single-month 38% drop in PSA testing was observed in April 2020; this corresponded to Australia's first wave. No change was observed in the rate of prostate biopsies. Peri-COVID-19 outbreaks, there was a slight shift toward the use of long-acting androgen deprivation therapy (ADT) at 4% with a predilection still for short-acting agents. with no registered change in the overall volume of radiotherapy or surgery. There were no deficits in the number of diagnostic and treatment activities for men with PC. Aside from a slight shift toward long-acting ADT use during the pandemic, no other patterns were observed. The longer-term impact such as missed diagnosis or late presentation affecting chances of survival due to COVID-19 is yet to be ascertained.

Integrative multi-omics analysis unveils stemness-associated molecular subtypes in prostate cancer and pan-cancer: prognostic and therapeutic significance.

BACKGROUND: Prostate cancer (PCA) is the fifth leading cause of cancer-related deaths worldwide, with limited treatment options in the advanced stages. The immunosuppressive tumor microenvironment (TME) of PCA results in lower sensitivity to immunotherapy. Although molecular subtyping is expected to offer important clues for precision treatment of PCA, there is currently a shortage of dependable and effective molecular typing methods available for clinical practice. Therefore, we aim to propose a novel stemness-based classification approach to guide personalized clinical treatments, including immunotherapy. METHODS: An integrative multi-omics analysis of PCA was performed to evaluate stemness-level heterogeneities. Unsupervised hierarchical clustering was used to classify PCAs based on stemness signature genes. To make stemness-based patient classification more clinically applicable, a stemness subtype predictor was jointly developed by using four PCA datasets and 76 machine learning algorithms. RESULTS: We identified stemness signatures of PCA comprising 18 signaling pathways, by which we classified PCA samples into three stemness subtypes via unsupervised hierarchical clustering: low stemness (LS), medium stemness (MS), and high stemness (HS) subtypes. HS patients are sensitive to androgen deprivation therapy, taxanes, and immunotherapy and have the highest stemness, malignancy, tumor mutation load (TMB) levels, worst prognosis, and immunosuppression. LS patients are sensitive to platinum-based chemotherapy but resistant to immunotherapy and have the lowest stemness, malignancy, and TMB levels, best prognosis, and the highest immune infiltration. MS patients represent an intermediate status of stemness, malignancy, and TMB levels with a moderate prognosis. We further demonstrated that these three stemness subtypes are conserved across pan-tumor. Additionally, the 9-gene stemness subtype predictor we developed has a comparable capability to 18 signaling pathways to make tumor diagnosis and to predict tumor recurrence, metastasis, progression, prognosis, and efficacy of different treatments. CONCLUSIONS: The three stemness subtypes we identified have the potential to be a powerful tool for clinical tumor molecular classification in PCA and pan-cancer, and to guide the selection of immunotherapy or other sensitive treatments for tumor patients.

The impact of NCCN-compliant multidisciplinary conference on the uptake of active surveillance among eligible patients with localized prostate cancer.

INTRODUCTION: We sought to investigate the impact of National Comprehensive Cancer Network (NCCN)-compliant multidisciplinary conference on the uptake of active surveillance (AS) among eligible patients with prostate cancer. METHODS: Retrospective review of our AS database was performed. Patients who are eligible for AS who sought a second opinion at a comprehensive cancer center (2010-2021) were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Cochrane Armitage test was used to examine trends over time. Multivariable regression models were fit to evaluate variables associated with the receipt of AS. RESULTS: Seven hundred twelve patients were identified (19% NCCN very low risk, 32% low risk, and 49% intermediate favorable risk). 43% were recommended AS as the preferred option by the community compared to 68% by LPCC, and 65% elected AS. Recommending AS significantly increased between 2010 and 2021 by the community (from 26% to 57%) and by LPCC (from 52% to 82%), while the proportion of men who received AS increased from 47% to 80% during the same period (P < 0.0001 for all). More recent LPCC era 2017 to 2021 (OR 12.31, 95% CI, 5.60-27.03, P < 0.0001), African American race (OR 0.42, 95% CI, 0.18-0.96, P = 0.04), positive cores at biopsy (OR 0.96, 95% CI, 0.94-0.97, P < 0.0001), age (OR 1.14, 95% CI, 1.10-1.18, P < 0.0001), NCCN low risk (OR 0.25, 95% CI, 0.08-0.81, P = 0.02) and NCCN intermediate favorable risk (OR 0.03, 95% CI, 0.01-0.09, P < 0.0001) were associated with receipt of AS. CONCLUSION: AS recommendation increased significantly over time by community urologists and to a higher extent by NCCN-compliant multidisciplinary conference. The Uptake of AS significantly increased within the same period. More recent LPCC era 2017 to 2021, African American race, the proportion of positive cores at biopsy, age, and NCCN risk were the main determinants of receipt of AS.

Survival Rate and Prognostic Factors of Localised Prostate Cancer in Southeast Asian Countries: A Systematic Review with Meta-Analysis.

Prostate cancer (Pca) is one of the most prevalent health conditions affecting men, particularly older men, and cases have increased in recent years. OBJECTIVE: This review examined the survival rate and prognostic factors of patients with Pca in Southeast Asia (SEA). METHODS: We conducted a systematic search of three databases (PubMed, Scopus, Web of Science) and a manual search until April 1, 2022. The selected papers were evaluated using the Newcastle-Ottawa Quality Assessment Form for Cohort Studies. The review protocol was registered with PROSPERO (CRD42022326521). Pooled prevalence rates were calculated using the programme R version 4.2.1. Heterogeneity was assessed using the I2 statistic and p-value. A narrative approach was used to describe prognostic factors. Studies were selected and finalised based on the review question. The quality of the included studies was assessed. RESULTS: A total of 11 studies were included in this review. The 1-, 3-, 5- and 10-year survival rates of SEA Pca cases were 80.8%, 51.9%, 66.1% (range 32.1-100) and 78% (range 55.9-100), respectively. Prognostic factors for Pca were discussed in terms of sociodemographic, disease-related and treatment-related aspects. The predictors of significantly lower survival were age more than 75 years, cancer detected during transurethral resection of the prostate, Gleason score more or equal to eight, high-risk group, metastases and no adjuvant radiotherapy. A meta-analysis on the pooled HR of prostate cancer could not be performed due to the heterogeneity of prognostic factors. The pooled prevalence of localised and metastatic prostate cancer in SEA countries was 39% 95% CI [20-62] and 40% 95% CI [28-53], respectively. CONCLUSION: The survival rate in SEA countries can be determined by prognostic factors, which can be divided into sociodemographic, disease-related and treatment-related factors. Therefore, further studies are needed to improve the understanding and treatment of Pca in the region SEA.

Use of the Decipher genomic classifier among men with prostate cancer in the United States.

BACKGROUND: Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer. METHODS: Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy. RESULTS: A total of 572 545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84). CONCLUSIONS: There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.

Cell-Membrane-Coated and Cell-Penetrating Peptide-Conjugated Trimagnetic Nanoparticles for Targeted Magnetic Hyperthermia of Prostate Cancer Cells.

Prostate malignancy represents the second leading cause of cancer-specific death among the male population worldwide. Herein, enhanced intracellular magnetic fluid hyperthermia is applied in vitro to treat prostate cancer (PCa) cells with minimum invasiveness and toxicity and highly specific targeting. We designed and optimized novel shape-anisotropic magnetic core-shell-shell nanoparticles (i.e., trimagnetic nanoparticles - TMNPs) with significant magnetothermal conversion following an exchange coupling effect to an external alternating magnetic field (AMF). The functional properties of the best candidate in terms of heating efficiency (i.e., Fe3O4@Mn0.5Zn0.5Fe2O4@CoFe2O4) were exploited following surface decoration with PCa cell membranes (CM) and/or LN1 cell-penetrating peptide (CPP). We demonstrated that the combination of biomimetic dual CM-CPP targeting and AMF responsiveness significantly induces caspase 9-mediated apoptosis of PCa cells. Furthermore, a downregulation of the cell cycle progression markers and a decrease of the migration rate in surviving cells were observed in response to the TMNP-assisted magnetic hyperthermia, suggesting a reduction in cancer cell aggressiveness.

Multifunctional nano-system for multi-mode targeted imaging and enhanced photothermal therapy of metastatic prostate cancer.

Prostate cancer (PCa) routinely employs magnetic resonance (MR) imaging, while metastatic PCa needs more complicated detection methods for precise localization. The inconvenience of using different methods to detect PCa and its metastases in patients and the limitations of single-mode imaging have brought great challenges to clinicians. Meanwhile, clinical treatments for metastatic PCa are still limited. Herein, we report a targeted theranostic platform of Au/Mn nanodots-luteinising hormone releasing hormone (AMNDs-LHRH) nano-system for multi-mode imaging guided photothermal therapy of PCa. The nano-system not only can simultaneously target Gonadotropin-Releasing Hormone Receptor (GnRH-R) positive PCa and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence (FL) visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. Meanwhile, the AMNDs-LHRH with promising targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic PCa. The AMNDs-LHRH nano-system guarantees the diagnostic accuracy and enhanced therapeutic effect, which provides a promising platform for clinical diagnosis and treatment of metastatic PCa. STATEMENT OF SIGNIFICANCE: Accurate clinical diagnosis and treatment of prostate cancer and its metastases is challenging. A targeted theranostic platform of AMNDs-LHRH nano-system for multi-mode imaging (FL/CT/MR) guided photothermal therapy of metastatic prostate cancer has been reported. The nano-system not only can simultaneously target prostate cancer and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. The nano-system with great targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic prostate cancer. Overall, the AMNDs-LHRH nano-system integrates tumor targeting, multi-mode imaging and enhanced therapeutic effect, which can provide an effective strategy for the clinical diagnosis and treatment of metastatic PCa.

Comprehensive genomic profiling and treatment patterns across ancestries in advanced prostate cancer: a large-scale retrospective analysis.

BACKGROUND: Men of African ancestry experience the greatest burden of prostate cancer globally, but they are under-represented in genomic and precision medicine studies. Therefore, we sought to characterise the genomic landscape, comprehensive genomic profiling (CGP) utilisation patterns, and treatment patterns across ancestries in a large, diverse, advanced prostate cancer cohort, to determine the impact of genomics on ancestral disparities. METHODS: In this large-scale retrospective analysis, the CGP-based genomic landscape was evaluated in biopsy sections from 11 741 patients with prostate cancer, with ancestry inferred using a single nucleotide polymorphism-based approach. Admixture-derived ancestry fractions for each patient were also interrogated. Independently, clinical and treatment information was retrospectively reviewed for 1234 patients in a de-identified US-based clinicogenomic database. Prevalence of gene alterations, including actionable gene alterations, was assessed across ancestries (n=11 741). Furthermore, real-world treatment patterns and overall survival was assessed in the subset of patients with linked clincogenomic information (n=1234). FINDINGS: The CGP cohort included 1422 (12%) men of African ancestry and 9244 (79%) men of European ancestry; the clinicogenomic database cohort included 130 (11%) men of African ancestry and 1017 (82%) men of European ancestry. Men of African ancestry received more lines of therapy before CGP than men of European ancestry (median of two lines [IQR 0-8] vs one line [0-10], p=0·029). In genomic analyses, ancestry-specific mutational landscapes were observed, but the prevalence of alterations in AR, the DNA damage response pathway, and other actionable genes were similar across ancestries. Similar genomic landscapes were observed in analyses that accounted for admixture-derived ancestry fractions. After undergoing CGP, men of African ancestry were less likely to receive a clinical study drug compared with men of European ancestry (12 [10%] of 118 vs 246 [26%] of 938, p=0·0005). INTERPRETATION: Similar rates of gene alterations with therapy implications suggest that differences in actionable genes (including AR and DNA damage response pathway genes) might not be a main driver of disparities across ancestries in advanced prostate cancer. Later CGP utilisation and a lower rate of clinical trial enrolment observed in men of African ancestry could affect genomics, outcomes, and disparities. FUNDING: American Society for Radiation Oncology, Department of Defense, Flatiron Health, Foundation Medicine, Prostate Cancer Foundation, and Sylvester Comprehensive Cancer Center.

Demographic disparities in receipt of care at a comprehensive cancer center.

BACKGROUND: National Cancer Institute cancer centers (NCICCs) provide specialized cancer care including precision oncology and clinical treatment trials. While these centers can offer novel therapeutic options, less is known about when patients access these centers or at what timepoint in their disease course they receive specialized care. This is especially important since precision diagnostics and receipt of the optimal therapy upfront can impact patient outcomes and previous research suggests that access to these centers may vary by demographic characteristics. Here, we examine the timing of patients' presentation at Moffitt Cancer Center (MCC) relative to their initial diagnosis across several demographic characteristics. METHODS: A retrospective cohort study was conducted among patients who presented to MCC with breast, colon, lung, melanoma, and prostate cancers between December 2008 and April 2020. Patient demographic and clinical characteristics were obtained from the Moffitt Cancer Registry. The association between patient characteristics and the timing of patient presentation to MCC relative to the patient's cancer diagnosis was examined using logistic regression. RESULTS: Black patients (median days = 510) had a longer time between diagnosis and presentation to MCC compared to Whites (median days = 368). Black patients were also more likely to have received their initial cancer care outside of MCC compared to White patients (odds ratio [OR] and 95% confidence interval [CI] = 1.45 [1.32-1.60]). Furthermore, Hispanics were more likely to present to MCC at an advanced stage compared to non-Hispanic patients (OR [95% CI] = 1.28 [1.05-1.55]). CONCLUSIONS: We observed racial and ethnic differences in timing of receipt of care at MCC. Future studies should aim to identify contributing factors for the development of novel mitigation strategies and assess whether timing differences in referral to an NCICC correlate with long-term patient outcomes.

Impact of an NCCN-Compliant Multidisciplinary Conference on Treatment Decisions for Localized Prostate Cancer.

BACKGROUND: We sought to investigate the impact of an NCCN-compliant multidisciplinary conference on treatment decisions of patients with localized prostate cancer. METHODS: A retrospective review of our quality assurance localized prostate cancer database was performed. All patients with localized prostate cancer who sought a second opinion at Roswell Park Comprehensive Cancer Center between 2009 and 2019 were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Multivariable regression models were fit to evaluate variables associated with concordance between community recommendations, LPCC recommendations, and treatment received by patients. RESULTS: A total of 1,164 patients were identified, of whom 26% had NCCN very low-/low-risk, 27% had favorable intermediate-risk, 25% had unfavorable intermediate-risk, and 22% had high-/very high-risk prostate cancer. Pathology changed in 11% of patients after genitourinary pathologist review, which caused disease reclassification in 9%. Concordance between community and LPCC recommendations occurred in 78%, with lowest concordance for androgen deprivation therapy (21%) and radiotherapy (53%). Concordance between community recommendations and treatment received occurred in 65%, with lowest concordance for androgen deprivation therapy and radiotherapy; among those who were recommended radiotherapy as the only option by their community urologist, only 26% received it. Concordance between LPCC recommendations and treatment received occurred in 92%. CONCLUSIONS: Community recommendations differed from the multidisciplinary NCCN-compliant recommendations in 22% of patients, primarily for radiotherapy. Multidisciplinary recommendations matched the treatment received in 92% of patients compared with 65% for community recommendations.

Nutrition Guidance for Patients on Androgen Deprivation Therapy.

Dietary guidance for men with prostate cancer on androgen deprivation therapy (ADT) should focus on reducing the risk of prostate cancer-specific outcomes and other chronic diseases, including cardiovascular disease (CVD). National guidelines for both CVD prevention and cancer survivors recommend a diet rich in fruits and vegetables and low in red/processed meat, refined grains, and added fats and sugars. Additional observational studies and randomized controlled trials are needed to examine short- and long-term effects of diet on clinical, biological, and patient-reported outcomes for men treated with ADT.

Delivering Genetic Testing for Patients with Prostate Cancer: Moving Beyond Provider Knowledge as a Barrier to Care.

INTRODUCTION: The 2018 National Comprehensive Cancer Network guidelines for prostate cancer genetic testing expanded access to genetic services. Few studies have examined how this change has affected provider practice outside of large cancer centers. METHODS: We conducted a qualitative study of multi-disciplinary health care providers treating patients with prostate cancer at a safety-net hospital. Participants completed an interview that addressed knowledge, practices, and contextual factors related to providing genetic services to patients with prostate cancer. A thematic analysis using both inductive and deductive coding was undertaken. RESULTS: Seventeen providers completed interviews. Challenges in identifying eligible patients for genetic testing stemmed from a lack of a) systems that facilitate routine patient identification, and b) readily available family history data for eligibility determination. Providers identified non-medical patient characteristics that influenced their referral process, including health literacy, language, cultural beliefs, patient distress, and cost. Providers who see patients at different times along the cancer care continuum viewed benefits of testing differently. CONCLUSION: The use of digital technologies that systematically identify those eligible for genetic testing referrals may mitigate some but not all challenges identified in this study. Further research should determine how individual provider perceptions influence referral practices and patient access to genetics both within and across cancer specialties.

Development of handheld induction heaters for magnetic fluid hyperthermia applications andin-vitroevaluation on ovarian and prostate cancer cell lines.

Objective:Magnetic fluid hyperthermia (MFH) is a still experimental technique found to have a potential application in the treatment of cancer. The method aims to reach around 41 °C-47 °C in the tumor site by exciting magnetic nanoparticles with an externally applied alternating magnetic field (AMF), where cell death is expected to occur. Applying AMFs with high spatial resolution is still a challenge. The AMFs from current and prospective MFH applicators cover relatively large areas; being not suitable for patients having metallic implants near the treatment area. Thus, there will be a clinical need for smaller magnetic field applicators. To this end, a laparoscopic induction heater (LIH) and a transrectal induction heater (TRIH) were developed.Methods:Miniature 'pancake' coils were wound and inserted into 3D printed enclosures. Ovarian (SKOV-3, A2780) and prostate (PC-3, LNCaP) cancer cell lines were used to evaluate the instruments' capabilities in killing cancer cellsin vitro, using Synomag®-D nanoparticles as the heat mediators. NIH3T3 normal cell lines were also used with both devices to observe if these cells tolerated the conditions applied.Results:Magnetic field intensities reached by the LIH and TRIH were 42.6 kA m-1at 326 kHz and 26.3 kA m-1at 303 kHz, respectively. Temperatures reached in the samples were 41 °C by the LIH and 43 °C by the TRIH. Both instruments successfully accomplished killing cancer cells, with minimal effects on normal cells.Conclusion:This work presents the first line of handheld medical induction heaters and have the potential to be a complement to existing cancer therapies.Significance:These instruments could enable the development of MFH modalities that will facilitate the clinical translation of this thermal treatment.

Non-pyrogenic highly pure magnetosomes for efficient hyperthermia treatment of prostate cancer.

We report the fabrication of highly pure magnetosomes that are synthesized by magnetotactic bacteria (MTB) using pharmaceutically compatible growth media, i.e., without compounds of animal origin (yeast extracts), carcinogenic, mutagenic, or toxic for reproduction (CMR) products, and other heavy metals than iron. To enable magnetosome medical applications, these growth media are reduced and amended compared with media commonly used to grow these bacteria. Furthermore, magnetosomes are made non-pyrogenic by being extracted from these micro-organisms and heated above 400 °C to remove and denature bacterial organic material and produce inorganic magnetosome minerals. To be stabilized, these minerals are further coated with citric acid to yield M-CA, leading to fully reconstructed chains of magnetosomes. The heating properties and anti-tumor activity of highly pure M-CA are then studied by bringing M-CA into contact with PC3-Luc tumor cells and by exposing such assembly to an alternating magnetic field (AMF) of 42 mT and 195 kHz during 30 min. While in the absence of AMF, M-CA are observed to be non-cytotoxic, they result in a 35% decrease in cell viability following AMF application. The treatment efficacy can be associated with a specific absorption rate (SAR) value of M-CA, which is relatively high in cellular environment, i.e., SARcell = 253 ± 11 W/gFe, while being lower than the M-CA SAR value measured in water, i.e., SARwater = 1025 ± 194 W/gFe, highlighting that a reduction in the Brownian contribution to the SAR value in cellular environment does not prevent efficient tumor cell destruction with these nanoparticles. KEY POINTS : • Highly pure magnetosomes were produced in pharmaceutically compatible growth media • Non-pyrogenic and stable magnetosomes were prepared for human injection • Magnetosomes efficiently destroyed prostate tumor cells in magnetic hyperthermia.

Utilization of genetic testing in men with advanced prostate cancer.

BACKGROUND: Genetic evaluation of men with advanced prostate cancer is recognized as imperative both to guide treatment decisions and to trigger cascade genetic testing of family members. Here we investigate utilization patterns of genetic testing among a contemporary cohort of men with advanced prostate cancer at our institution. METHODS: We queried the Northwestern Electronic Data Warehouse from January 2021 to present for all men diagnosed with National Comprehensive Cancer Network high-risk/very high-risk, regional, or metastatic prostate cancer. Patients were excluded from analyses if treated at an outside institution and/or presented for a second opinion evaluation. Statistics were performed using t-test, Chi-squared test, and univariable and multivariable logistic regression with significance defined as p < 0.05. RESULTS: Atotal of 320 men (52.5%) had local/regional disease and 290 (47.5%) had metastatic disease, 53 (18.3%) of whom had castrate resistant prostate cancer. Rates of germline genetic testing rate were low in patients with localized disease (9.4%) and metastatic disease (34.1%). Only 19 (35.8%) men diagnosed with metastatic castrate resistant prostate cancer underwent germline genetic evaluation. Germline testing was most frequently discussed or ordered by medical oncologists (52%) followed by urologists (20%). Men who underwent germline testing were younger (p < 0.001), more likely to have Medicaid or private insurance (p = 0.002), and more likely to have metastatic disease (p < 0.001). There were no statistically significant differences in baseline PSA, ethnicity, race, or castration sensitivity status. Age (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.91-0.97, p < 0.001) and metastatic disease (OR: 5.71, 95% CI: 3.63-9.22, p < 0.001) were significant independent predictors of genetic testing on multivariable logistic regression. CONCLUSIONS: Here we report that utilization of genetic testing is associated with metastatic disease and inversely associated with age. Overall, utilization rates of genetic testing remain low in all patient groups, including in the metastatic castrate resistant setting, where genetic testing can identify patients with homologous recombination repair deficiency who may benefit from use of targeted therapeutics such as PARP inhibitors. Genetic testing in men with aggressive prostate cancer is critical and barriers to routine implementation of testing require further study to develop strategies to improve utilization rates.