Long-Term Performance of Prognostic Models for Advanced Renal Cell Carcinoma in the Era of Improved Survival With Immune Checkpoint Inhibitors.

Purpose: In the era of prolonged survival for advanced renal cell carcinoma (aRCC) with standard-of-care first-line therapy now including immune checkpoint inhibitor, re-evaluation of the Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic RCC Database Consortium (IMDC) prognostic models is overdue.

Methods: Data from 1,052 patients with aRCC treated on the CheckMate-214 phase III randomized trial with first-line nivolumab + ipilimumab or sunitinib were analyzed after minimum 5 years of follow-up. The end point was overall survival (OS).

Tumor-Intrinsic and Microenvironmental Determinants of Impaired Antitumor Immunity in Chromophobe Renal Cell Carcinoma.

Purpose: While immune checkpoint inhibition (ICI) has transformed the management of many advanced renal cell carcinomas (RCCs), the determinants of effective antitumor immunity for chromophobe RCC (ChRCC) and renal oncocytic tumors remain an unmet clinical and scientific need.

Methods: Single-cell transcriptomic and T-cell receptor profiling was performed on tumor and adjacent normal tissue of patients with ChRCC and renal oncocytic neoplasms. Using machine learning, the cellular origin of renal oncocytic neoplasms was evaluated, with analysis of associated oncogenic pathways.

International Medical Graduates Representation at International Oncology Conference Meetings: An Analysis of ASCO Annual Meetings.

Purpose: Despite international medical graduates (IMGs) accounting for up to one third of all practicing oncologists in the United States, and nearly half of fellowship trainees, little is known about their contributions to presentations at international oncology meetings. Therefore, we investigated the representation of IMGs in invited faculty roles at the ASCO Annual Meeting as a representative example.

Methods: Presentation data from ASCO 2022 and 2023 Annual Meetings were obtained from program guides.

Race and Outcomes to [Lu]Lu-PSMA-617 in Advanced Prostate Cancer.

Black patients with metastatic prostate cancer have higher mortality rates compared to non-Hispanic White patients. There are no data on outcomes with [Lu]Lu-PSMA-617 (LuPSMA) across racial groups. We evaluated the association between race and outcomes with LuPSMA in a multi-institutional cohort of consecutive patients with mCRPC treated with LuPSMA.

CDK4/6 Inhibition With Abemaciclib in Patients With Previously Treated Advanced Renal Cell Carcinoma.

Background: Preclincal data provide a rationale for cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors alone and in combination with HIF-2α inhibitors in treatment of clear cell renal cell carcinoma (ccRCC), with randomized phase 2 clinical trials currently open exploring the combination of palbociclib with belzutifan vs belzutifan in treatment resistant ccRCC (NCT05468697). However, single agent activity for CDK4/6 inhibitors in ccRCC has not been reported. In this multi-center phase 1b clinical trial (NCT04627064), we investigated the safety and efficacy of monotherapy with abemaciclib, an oral CDK4/6 inhibitor in patients with advanced pretreated RCC.

Long-term Outcomes and Prognostic Impact of Residual Cancer Burden After Intensified Neoadjuvant Therapy in High-risk Prostate Cancer.

Background And Objective: Long-term outcomes and the prognostic impact of the extent of residual disease after neoadjuvant therapy (NAT) with androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) before radical prostatectomy (RP) for high-risk localized prostate cancer (HRLPC) are not known.

Methods: We analyzed data for patients treated in five trials evaluating 6 mo of ARPI NAT for HRLPC at our institution between 2006 and 2018. Residual cancer burden (RCB) was quantitated as the calculated tumor volume adjusted for cellularity in the primary tumor.

Treatment-free Survival After First-line Therapies for Metastatic Renal Cell Carcinoma: An International Metastatic Renal Cell Carcinoma Database Consortium Analysis.

Background And Objective: Patients receiving immune checkpoint blockade (ICB) therapy may experience periods of prolonged disease control without a need for systemic therapy. Treatment-free survival (TFS) is an important measure for this period, but no data are available for patients with metastatic renal cell carcinoma (mRCC) starting first-line agents. Our aim was to analyze TFS outcomes for patients with mRCC starting first-line therapy.

Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma.

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers.

Refining Risk Stratification of High-risk and Locoregional Prostate Cancer: A Pooled Analysis of Randomized Trials.

Background And Objective: Radiotherapy (RT) and long-term androgen deprivation therapy (ltADT; 18-36 mo) is a standard of care in the treatment of high-risk localized/locoregional prostate cancer (HRLPC). We evaluated the outcomes in patients treated with RT + ltADT to identify which patients have poorer prognosis with standard therapy.

Methods: Individual patient data from patients with HRLPC (as defined by any of the following three risk factors [RFs] in the context of cN0 disease-Gleason score ≥8, cT3-4, and prostate-specific antigen [PSA] >20 ng/ml, or cN1 disease) treated with RT and ltADT in randomized controlled trials collated by the Intermediate Clinical Endpoints in Cancer of the Prostate group.

Plasma Kidney Injury Molecule-1 for Preoperative Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association With Clinical Outcomes.

Purpose: Both clear cell and papillary renal cell carcinomas (RCCs) overexpress kidney injury molecule-1 (KIM-1). We investigated whether plasma KIM-1 (pKIM-1) may be a useful risk stratification tool among patients with suspicious renal masses.

Methods: Prenephrectomy pKIM-1 was measured in two independent cohorts of patients with renal masses.

Intermediate clinical endpoints in early-stage breast cancer: an analysis of individual patient data from the Gruppo Italiano Mammella and Mammella Intergruppo trials.

Background: Intermediate clinical endpoints (ICEs) are frequently used as primary endpoint in randomised trials (RCTs). We aim to assess whether changes in different ICEs can be used to predict changes in overall survival (OS) in adjuvant breast cancer trials.

Methods: Individual patient level data from adjuvant phase III RCTs conducted by the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo (MIG) study groups were used.

Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens.

Background: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens.

Materials And Methods: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively.

Impact of renal cell carcinoma molecular subtypes on immunotherapy and targeted therapy outcomes.

Saliby et al. show that a machine learning approach can accurately classify clear cell renal cell carcinoma (RCC) into distinct molecular subtypes using transcriptomic data. When applied to tumors biospecimens from the JAVELIN Renal 101 (JR101) trial, a benefit is observed with immune checkpoint inhibitor (ICI)-based therapy across all molecular subtypes.

Discover overlooked complications after preeclampsia using electronic health records.

Background: Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and end-organ damage such as proteinuria. PE poses a significant threat to women's long-term health, including an increased risk of cardiovascular and renal diseases. Most previous studies have been hypothesis-based, potentially overlooking certain significant complications.

Discover overlooked complications after preeclampsia from three real-world medical record datasets of over 100,000 pregnancies.

Importance: Preeclampsia poses a significant threat to women's long-term health. However, what diseases are affected and at what level they are affected by PE needs a thorough investigation.

Objective: To conduct the first large-scale, non-hypothesis-driven study using EHR data from multiple medical centers to comprehensively explore adverse health outcomes after preeclampsia.

Radiographic Progression-Free Survival and Clinical Progression-Free Survival as Potential Surrogates for Overall Survival in Men With Metastatic Hormone-Sensitive Prostate Cancer.

Purpose: Despite major increases in the longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC), most men still die of prostate cancer. Phase III trials assessing new therapies in mHSPC with overall survival (OS) as the primary end point will take approximately a decade to complete. We investigated whether radiographic progression-free survival (rPFS) and clinical PFS (cPFS) are valid surrogates for OS in men with mHSPC and could potentially be used to expedite future phase III clinical trials.

Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

Background: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.

Adjuvant and salvage radiotherapy after neoadjuvant therapy and radical prostatectomy for high-risk localized prostate cancer.

Background: We sought to describe patterns of delivery of adjuvant (aRT) and salvage RT (sRT) in patients who underwent RP after receiving neoadjuvant androgen receptor pathway inhibitor (ARPI) before radical prostatectomy (RP) for high-risk localized prostate cancer (HRLPC).

Methods: Two hundred eighteen patients treated on phase 2 neoadjuvant trials between 2006 and 2018 at two academic centers were evaluated. aRT and sRT were defined as receipt of RT with a PSA of ≤0.