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Simple Summary: Many of the current data on outcomes in metastatic non-small cell lung cancer (NSCLC) stem from patients who were diagnosed in the ambulatory setting. This study aimed to investigate patients who receive new diagnoses of metastatic NSCLC while they are inpatients. Specifically, we sought to evaluate how many patients receive systemic therapy as well as the overall population's survival outcomes and palliative care utilization in order to help guide treatment for future cases. Purpose: The usual workup for patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) occurs in the ambulatory setting. A subset of patients present with acute care needs and receive the diagnosis while hospitalized. Palliative therapies are typically initiated when patients are outpatients, even when diagnoses are made when they are inpatients. Lengthy admission, rehabilitation needs after discharge, and readmissions are possible barriers to timely and adequate outpatient follow-up. The outcomes for these patients diagnosed in the hospital are not well characterized. We hypothesized that patients have been ill-served by current treatment patterns, as reflected by low rates of cancer-directed treatment and poor survival. Patients and methods: We performed a retrospective study of new inpatient diagnoses of metastatic NSCLC at our institution between 1 January 2012 and 1 January 2022. The primary outcome was the proportion of patients ultimately receiving cancer-directed therapy. Other outcomes included time to treatment, use of targeted therapy, palliative care/hospice utilization, and overall survival (OS). Results: Seventy-three patients were included, with a median age of 57 years. Twenty-seven patients (37%) ultimately received systemic therapy with a median time from diagnosis to treatment of 37.5 days. Overall, 5.4% patients died while admitted, 6.8% were discharged to a hospice, 21.9% were discharged to a facility, and 61.6% were discharged home. Only 20 patients (27%) received palliative care consultation. The median OS for our entire population was 2.3 months, with estimated 6-month and 1-year OS rates of 32% and 22%, respectively. Conclusion: Patients with new inpatient diagnoses of metastatic NSCLC have extremely poor outcomes. Current management strategies resulted in few patients starting systemic therapy, yet most of the patients did not receive palliative care or hospice involvement. These findings demonstrate that there is a high unmet need to optimally support and palliate these patients. [ABSTRACT FROM AUTHOR]

Purpose: The treatment approach for non-metastatic bladder cancer is guided by an invasion of the muscular layer of the bladder wall. Radical cystectomy is the recommended treatment for muscle-invasive disease. However, it has considerable morbidity and mortality and is not suited for many patients. Trimodality therapy consisting of chemoradiation after transurethral resection of bladder tumor offers a definitive approach with bladder-sparing potential. However, there is a lack of research defining the optimal combination of chemotherapy and radiation in this setting. Materials and Methods: We extracted patient data from the National Cancer Database to compare survival outcomes and demographic factors in 2,227 non-metastatic bladder cancer patients who were treated with chemotherapy sequential to or concurrently with radiation. Sequential treatment was defined as chemotherapy beginning >14 days before radiation, and concurrent was defined as beginning within 14 days of the first radiation. Results: The sequential treatment group patients were younger (mean age, 74 vs. 78 years; p < 0.001) with more advanced disease. We found no difference in overall survival between patients who received chemotherapy sequential to radiation and those who received concurrent chemoradiation only (p = 0.533). Conclusion: Our data are concordant with a previous prospective study, and support that chemotherapy prior to radiation does not decrease survival outcomes relative to patients receiving only concurrent chemoradiation. Given that the sequential group had an overall higher stage but no difference in survival, downstaging chemotherapy prior to radiation may be helpful in these patients. Further studies including a larger, multi-institutional clinical trial are indicated to support clinical decision-making. [ABSTRACT FROM AUTHOR]

PARP inhibition in prostate cancer has become a standard-of-care option for men with metastatic castration-resistant prostate cancer (mCRPC) with deficiency in homologous recombination repair (HRRd). The benefit varies based upon the characteristics of the PARP inhibitor used and the underlying HRR defect. Optimal patient selection remains a clinical challenge, and investigations are underway to identify effective combination therapies to expand the population that benefits. We review the clinical development of the FDA-approved PARP inhibitors olaparib and rucaparib. Additionally, we explore the status of other PARP inhibitors that remain experimental in prostate cancer, based upon review of published abstracts, articles, and clinicaltrials.gov. Most new studies, including phase 3 trials for talazoparib and rucaparib, involve combinations with novel androgen receptor signaling inhibitors. We review the landscape of emerging PARP inhibitor-based combination therapies. For men with BRCA1 or BRCA2 mutations, olaparib has a clear role for early use in the disease course of mCRPC. For men with other HRR mutations, that benefit remains less well defined, particularly with the availability of other treatment choices. Ultimately, combination strategies are likely to be the best avenue for men without BRCA1 or BRCA2 mutations to be treated with PARP inhibition. [ABSTRACT FROM AUTHOR]

Nanoparticles and microparticles have many potential biomedical applications ranging from imaging to drug delivery. Therefore, in vitro systems that can analyze and optimize the interaction of such particles with cells may be beneficial. Here, we report a microfluidic system that can be used to study these interactions. As a model system, we evaluated the interaction of polymeric nanoparticles and microparticles and similar particles conjugated to aptamers that recognize the transmembrane prostate specific membrane antigen (PSMA), with cells seeded in microchannels. The binding of particles to cells that expressed or did not express the PSMA (LNCaP or PC3, respectively) were evaluated with respect to changes in fluid shear stress, PSMA expression on target cells, and particle size. Nanoparticle-aptamer bioconjugates selectively adhered to LNCaP but not PC3 cells at static and low shear (< 1 dyn/[cm.sup.2]) but not higher shear (~4.5 dyn/ [cm.sup.2]) conditions. Control nanoparticles and microparticles lacking aptamers and microparticle-aptamer bioconjugates did not adhere to LNCaP cells, even under very low shear conditions (~0.28 dyn/[cm.sup.2]). These results demonstrate that the interaction of particles with cells can be studied under controlled conditions, which may aid in the engineering of desired particle characteristics. The scalability, low cost, reproducibility, and high-throughput capability of this technology is potentially beneficial to examining and optimizing a wide array of cell-particle systems prior to in vivo experiments.

PURPOSE: Clinical trials, which led to the approval of immune checkpoint inhibitors (ICI), have been almost exclusively performed in patients with good Eastern Cooperative Oncology Group performance status (ECOG PS of 0-1). However, ICI remains an attractive option for patients with advanced tumors and poor PS. We hypothesized that patients with ECOG PS ≥ 2 would have worse outcomes with ICI. METHODS: We retrospectively identified patients with advanced solid tumors who were treated with ICI at our institution. The log-rank test compared the survival among patients with different ECOG PS. We used a proportional hazards model to assess association between ECOG PS and overall survival (OS) with adjustment for covariates including age, sex, malignancy type, time from advance disease diagnosis, and line of therapy. We compared overall response rates between groups with Pearson chi-square exact test. We also analyzed in-hospital mortality and hospice referral rates. RESULTS: We identified 257 patients treated with ICI. One hundred eighty-two patients had ECOG PS 0-1, and 75 had ECOG PS ≥ 2. The median overall survival was 12.6 months for the ECOG PS 0-1 group compared with 3.1 months for the ECOG PS ≥ 2 group (P < .001). The overall response rate for patients with ECOG PS 0-1 was 23% compared with 8% for those with poor PS (P = .005). Patients with poor PS treated with ICI had similar hospice referral rates (67% for ECOG PS ≥ 2 v 61.9% for ECOG PS 0-1, P = .50) but were more likely to have in-hospital death as compared with the good PS group (28.6% v 15.1%, P = .035). CONCLUSION: Despite the appeal of ICI in patients with advanced malignancy and poor PS, outcomes in this cohort were poor. Prospective trials defining the activity and role of ICI in poor PS are urgently needed. [ABSTRACT FROM AUTHOR]

The article presents the treatment options available for advanced prostate cancer. Topics include F-18 fluciclovine and C-11 positron emission tomography (PET) modalities being approved by the Food and Drug Administration (FDA) for cases of biochemical recurrence after prior treatment; and study of Androgen Ablation Therapy with or without Chemotherapy in treating patients with Metastatic Prostate Cancer (CHAARTED).

Introduction: Common recurrent genetic alterations have been identified in prostate cancer through comprehensive sequencing efforts, and the prevalence of mutations in DNA repair pathway genes in patients with advanced and metastatic disease approaches 20–25%. Identification of these underlying DNA repair defects may present unique treatment opportunities for patients, both in terms of standard-of-care treatments and selected investigational agents. Areas covered: We review our current understanding of the genomic landscape of prostate cancer, with special attention to alterations in DNA repair pathway genes in metastatic castration-resistant disease. For patients with tumors deficient in homologous recombination repair, potential opportunities for treatment include platinum chemotherapy, poly(ADP) ribose polymerase (PARP) inhibitors, bipolar androgen therapy, and maybe immune checkpoint blockade therapy. In addition, tumors with mismatch repair defects (i.e. microsatellite instability) may be particularly susceptible to checkpoint blockade immunotherapy. Expert commentary: We anticipate that genomic profiling of tumors will become necessary to guide treatment of advanced prostate cancer in the coming years. Work is needed to define the optimal tissue to test, and to define the natural history of tumors with specific genetic defects. The prognostic and therapeutic importance of germlinevssomatic DNA repair alterations, and mono-allelicvsbi-allelic inactivation, also remains unclear. Finally, optimal strategies to sequence or combine targeted agents for these patients with ‘actionable’ mutations are now needed. [ABSTRACT FROM PUBLISHER]

Simple Summary: Prostate cancer is a leading cause of cancer-related death among males. Many treatments are available to manage the disease, but despite this, ultimately advanced prostate cancer is incurable and fatal. In order to improve survival and minimize side effects from these various treatments, the treatments need to be given in an optimal sequence or combination. This optimal use of therapies must be individualized, and biomarkers can be used for these decisions. Biomarkers can be useful in predicting whether a patient will respond to a treatment option and may help avoid use of therapies that are not expected to be effective. Many biomarkers are already in clinical use while many others are currently being investigated and may become part of clinical practice in future. In this review, we discuss both established and novel biomarkers with a role in management of advanced prostate cancer. Multiple treatment options with different mechanisms of action are currently available for the management of metastatic prostate cancer. However, the optimal use of these therapies—specifically, the sequencing of therapies—is not well defined. In order to obtain the best clinical outcomes, patients need to be treated with the therapies that are most likely to provide benefit and avoid toxic therapies that are unlikely to be effective. Ideally, predictive biomarkers that allow for the selection of the therapies most likely to be of benefit would be employed for each treatment decision. In practice, biomarkers including tumor molecular sequencing, circulating tumor DNA, circulating tumor cell enumeration and androgen receptor characteristics, and tumor cell surface expression (PSMA), all may have a role in therapy selection. In this review, we define the established prognostic and predictive biomarkers for therapy in advanced prostate cancer and explore emerging biomarkers. [ABSTRACT FROM AUTHOR]

Background: Sarcomatoid urothelial cancer of the bladder (SBC) is a rare, but aggressive histological subtype for which novel treatments are needed., Objective: We evaluated the clinical activity and safety of neoadjuvant cisplatin plus gemcitabine plus docetaxel (CGD) in muscle-invasive patients with SBC and assessed SBC tumor biology by whole transcriptome RNA sequencing., Methods: A single-institution, retrospective analysis of muscle-invasive SBC patients treated with neoadjuvant CGD with molecular analysis. Patients received cisplatin 35 mg/m2 + gemcitabine 800 mg/m2 + docetaxel 35 mg/m2 intravenously on days 1 and 8 + pegfilgrastim 6 mg subcutaneously on day 9 every 3 weeks for 4 cycles followed by cystectomy. The primary endpoint was pathologic complete response (ypCR) rate., Results: Sixteen patients with SBC received neoadjuvant CGD with a ypCR rate of 38% and a  < ypT2 rate of 50%. Grade 3 and 4 toxicity occurred in 80% and 40% of patients, but was manageable with 81% of patients completing > 3 CGD cycles. Whole transcriptome RNA sequencing demonstrates co-clustering of SBC with conventional urothelial tumors. SBC tumors are characterized by basal-squamous and stroma rich gene signatures with frequent increased expression of immune checkpoint ( CD274 (PD-L1)), chemokine ( CXCL9 ), and T-cell ( CD8A ) genes., Conclusions: SBC is a chemosensitive subtype, with ypCR rate similar to urothelial bladder cancer following CGD neoadjuvant therapy. Whole transcriptome tissue analyses demonstrate increased expression of immune checkpoint and T-cell genes with therapeutic implications., Competing Interests: Noah Hahn discloses consulting compensation from AstraZeneca, Merck, BioGears, Seattle Genetics, Mirati, Incyte, RemGen, Janssen, Pfizer, EMD Serono, Verity Pharmaceuticals, Huron Consulting, Guidepoint, Natera, Protara Therapeutics, Astellas Pharma, Trya Biosciences; research support to the institution from HTG Molecular Diagnostics, AstraZeneca, Bristol Myers-Squibb, Genentech, Seattle Genetics, Pieris, Inovio, Principia Biopharm, Incyte, Loxo Oncology, and Ikena Oncology; speaking honorarium from Medscape. Max Kates discloses consulting compensation from Genesis Biotech, Janssen, Pacific Edge, and FerGene. Andres Matoso discloses consulting compensation from PathAI. Burles A. Johnson III discloses serving as an unpaid member of Seattle Genetics Emerging Thought Leaders Advisory Board. Burles A. Johnson III, Noah Hahn, Jean Hoffman-Censits, and David McConkey are co-authors on a provisional US patent for an immune-based biomarker to predict response to immunotherapy in patients with advanced bladder cancer. T.J.B., J.H-C., N.M.H., and D.J.M. are on the Editorial Board of this journal, but these individuals were not involved in the peer-review process nor had access to any information regarding its peer-review., (© 2024 – The authors. Published by IOS Press.)

The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel's discussions for the 2024 update to the guidelines with regard to initial risk stratification, initial management of very-low-risk disease, and the treatment of nonmetastatic recurrence.

Prostate cancer, one of the most frequently diagnosed cancers in men, leads to significant mortality worldwide. Its study is important due to the complexity and diversity in its progression, highlighting the urgent need for improved therapeutic strategies. This chapter probes into the genetic and epigenetic factors influencing prostate cancer progression, underscoring the importance of understanding the disease's molecular fundamentals for the development of targeted therapies. It specifically reviews the role of key genetic mutations in genes such as Androgen Receptor, TP53, SPOP, FOXA1 and PTEN which are crucial for the disease onset and a progression. Furthermore, it examines the impact of epigenetic modifications, including DNA methylation and histone modification, which contribute to the cancer's progression by affecting gene expression and cellular behavior. Further, in this chapter we delve into the underlying signaling mechanism, the advancements in targeting genetic and epigenetic alterations in prostate cancer. These findings have revealed promising targets for therapeutic advancements, aiming to understand and identify promising avenues for future therapies. This chapter improves our current understanding of prostate cancer genetic and epigenetic landscape, emphasizing the necessity of advancing our knowledge to refine and expand treatment options for prostate cancer patients., (Copyright © 2024. Published by Elsevier Inc.)

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions regarding the workup of patients with prostate cancer, risk stratification and management of localized disease, post-treatment monitoring, and treatment of recurrence and advanced disease. The Guidelines sections included in this article focus on the management of metastatic castration-sensitive disease, nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). Androgen deprivation therapy (ADT) with treatment intensification is strongly recommended for patients with metastatic castration-sensitive prostate cancer. For patients with nonmetastatic CRPC, ADT is continued with or without the addition of certain secondary hormone therapies depending on prostate-specific antigen doubling time. In the mCRPC setting, ADT is continued with the sequential addition of certain secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies. The NCCN Prostate Cancer Panel emphasizes a shared decision-making approach in all disease settings based on patient preferences, prior treatment exposures, the presence or absence of visceral disease, symptoms, and potential side effects.

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, recurrent, and metastatic disease. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. These NCCN Guidelines Insights summarizes much of the panel's discussions for the 4.2022 and 1.2023 updates to the guidelines regarding systemic therapy for metastatic prostate cancer.