Tumour evolution and microenvironment interactions in 2D and 3D space.

To study the spatial interactions among cancer and non-cancer cells, we here examined a cohort of 131 tumour sections from 78 cases across 6 cancer types by Visium spatial transcriptomics (ST). This was combined with 48 matched single-nucleus RNA sequencing samples and 22 matched co-detection by indexing (CODEX) samples. To describe tumour structures and habitats, we defined 'tumour microregions' as spatially distinct cancer cell clusters separated by stromal components.

A Podcast on Practical Considerations in Patients with Advanced Urothelial Cancer Receiving First-Line Cisplatin- or Carboplatin-Based Chemotherapy Followed by Avelumab Maintenance in a Changing Therapeutic Landscape.

Platinum-based chemotherapy has been the cornerstone of first-line treatment for advanced urothelial carcinoma for decades, based on its proven efficacy and well-characterized safety profile. Although enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy versus platinum-based chemotherapy in the EV-302 phase 3 trial, common and potentially cumulative toxicities associated with EV plus pembrolizumab may make this combination less suitable for some patients, such as those with pre-existing neuropathy, hyperglycemia, or hepatic impairment, or patients likely to have favorable outcomes with platinum-based chemotherapy. The availability of EV plus pembrolizumab in various countries may also be limited by financial considerations.

Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial.

Purpose: CDK12 inactivation in metastatic castration-resistant prostate cancer (mCRPC) may predict immunotherapy responses. This phase 2 trial evaluated the efficacy of immune checkpoint inhibitor (ICI) therapy in patients with CDK12-altered mCRPC.

Patients And Methods: Eligible patients had mCRPC with deleterious CDK12 alterations and any prior therapies except ICI.

Incidental Coronary Arterial Calcification for Cardiovascular Risk Assessment in Men With Prostate Cancer Undergoing PET/CT Imaging.

Background: Cardiovascular (CV) disease is common among men with prostate cancer and the leading cause of death in this population. There is a need for CV risk assessment tools that can be easily implemented in the prostate cancer treatment setting.

Methods: Consecutive patients who underwent positron emission tomography/computed tomography (PET/CT) for recurrent prostate cancer at a single institution from 2012 to 2017 were identified retrospectively.

Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma.

Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival.

Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness.

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases.

Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases.

Background: Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions.

Pilot Study: PARP1 Imaging in Advanced Prostate Cancer.

Purpose: PARP inhibitor (PARPi) therapy is approved for patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) genomic aberrations. However, only a fraction of patients with BRCA1/2 mutations respond to PARPi therapy. In this pilot study, we assess PARP-1 expression in prostate cancer patients with and without HRR genomic alternations using a novel PARP-based imaging agent.

Prostate Cancer With Peritoneal Carcinomatosis: A Robotic-assisted Radical Prostatectomy-based Case Series.

Objective: To aid in the diagnosis and treatment of patients with metastatic tumor seeding, an exceedingly rare phenomenon following minimally invasive urological surgery, additional case reports are needed.

Materials And Methods: We report our experience with patients determined to have peritoneal carcinomatosis following robotic-assisted radical prostatectomy (RARP) and provide a descriptive summary of these unique cases.

Results: Five cases of peritoneal carcinomatosis were identified, all of which occurred relatively late-between 8 and 13 years-following RARP.

Correction: Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.

Commercial ctDNA Assays for Minimal Residual Disease Detection of Solid Tumors.

The detection of circulating tumor DNA via liquid biopsy has become an important diagnostic test for patients with cancer. While certain commercial liquid biopsy platforms designed to detect circulating tumor DNA have been approved to guide clinical decisions in advanced solid tumors, the clinical utility of these assays for detecting minimal residual disease after curative-intent treatment of nonmetastatic disease is currently limited. Predicting disease response and relapse has considerable potential for increasing the effective implementation of neoadjuvant and adjuvant therapies.

Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study.

Background: The standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability to offer bladder-sparing treatment. Here, we sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis.

Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS).

Purpose: The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known.

Materials And Methods: We queried the U.S.

Differential treatment outcomes in BRCA1/2-, CDK12-, and ATM-mutated metastatic castration-resistant prostate cancer.

Background: DNA damage repair mutations (DDRm) are common in patients with metastatic castration-resistant prostate cancer (mCRPC). The optimal standard therapy for this population is not well described.

Methods: A multi-institutional, retrospective study of patients with mCRPC and DDRm was conducted.

Immunotherapy and Immunotherapy Combinations in Metastatic Castration-Resistant Prostate Cancer.

Although most prostate cancers are localized, and the majority are curable, recurrences occur in approximately 35% of men. Among patients with prostate-specific antigen (PSA) recurrence and PSA doubling time (PSADT) less than 15 months after radical prostatectomy, prostate cancer accounted for approximately 90% of the deaths by 15 years after recurrence. An immunosuppressive tumor microenvironment (TME) and impaired cellular immunity are likely largely responsible for the limited utility of checkpoint inhibitors (CPIs) in advanced prostate cancer compared with other tumor types.

Elective Cytoreductive Nephrectomy After Checkpoint Inhibitor Immunotherapy in Patients With Initially Unresectable Metastatic Clear Cell Renal Cell Carcinoma.

Background:: Combination checkpoint inhibitor immunotherapy has recently become a new frontline standard of care for metastatic renal cell carcinoma (mRCC). Previously published data has demonstrated a survival benefit of cytoreductive nephrectomy (CN) in the interferon era, but the utility of CN in conjunction with the use of tyrosine kinase inhibitors (TKIs) has been controversial.

Patients:: In the current case series, we report on five patients with IMDC intermediate- or poor-risk initially unresectable metastatic renal cell carcinoma who successfully underwent CN.

Clinical Outcomes in Cyclin-dependent Kinase 12 Mutant Advanced Prostate Cancer.

Background: Cyclin-dependent kinase 12 (CDK12) loss occurs in 3-7% of metastatic prostate cancer patients and is characterized by a genomic instability signature, but the clinical implications of CDK12 loss are not well established.

Objective: To determine the clinical course of patients with CDK12 mutant advanced prostate cancer compared with other genomic subtypes.

Design, Setting, And Participants: A retrospective analysis of data from three academic medical centers, including 317 patients with advanced prostate cancer and prior next-generation sequencing from tumor tissue (n = 172) or circulating tumor DNA (n = 145), was performed.

Immunotherapy in Metastatic Castration-Resistant Prostate Cancer: Past and Future Strategies for Optimization.

Purpose Of Review: To date, prostate cancer has been poorly responsive to immunotherapy. In the current review, we summarize and discuss the current literature on the use of vaccine therapy and checkpoint inhibitor immunotherapy in metastatic castration-resistant prostate cancer (mCRPC).

Recent Findings: Sipuleucel-T currently remains the only FDA-approved immunotherapeutic agent for prostate cancer.

Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma.

Background Pazopanib is approved for metastatic renal cell carcinoma (RCC). We assessed the safety and efficacy of pazopanib with a low fat meal (LFM): <400 cal and < 20% fat or 10 g per meal. Methods A single arm study of pazopanib with a LFM in 16 adult patients with metastatic RCC with a clear cell component, RECIST 1.

Use of Bone-Modifying Agents in Myeloma and Bone Metastases: How Recent Dosing Interval Studies Have Affected Our Practice.

The management of bone lesions from advanced solid tumors and multiple myeloma typically includes use of a bone-modifying agent to reduce the risk of skeletal-related events. Recent data demonstrate that when using zoledronic acid to reduce the risk of skeletal-related events in metastatic breast cancer, metastatic prostate cancer, and multiple myeloma, the dosing interval of zoledronic acid may be extended from every 4 weeks to every 12 weeks. The ASCO guidelines on the role of bone-modifying agents in metastatic breast cancer and multiple myeloma address zoledronic acid dosing intervals.