Robin, Tyler P.

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 on select 2026 updates to the guidelines regarding nonmetastatic disease: the elimination of the very-low-risk group, updates to the Principles of Active Surveillance, and caution in the use of focal therapy in newly diagnosed patients.

TPS577 Background: Pembrolizumab (pembro) for one year following resection of localized high risk clear cell renal cell carcinoma (ccRCC) in a phase 3 trial resulted in improvement in relapse-free survival and overall survival (Choueiri, NEJM 2024). However, 20% of patients still experienced a relapse within 2 years with no biomarker yet identified to predict who will respond to or needs adjuvant therapy. Addition of a tyrosine kinase inhibitor (TKI) to immunotherapy (IO) is a standard of care in metastatic ccRCC, but to date no studies have addressed the addition of a TKI to IO in the adjuvant setting. Subsequently, phase 3 STRIKE! was developed to explore the benefit of 6 months of tivozanib (tivo) added to pembro vs pembro alone in the adjuvant setting for resected high risk ccRCC. Methods: Eligible patients have an ECOG performance status ≤2 and a histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features after complete resection of the primary tumor, with pathology revealing pT2 grade 4 disease or any grade ≥ T3 or TxN1. Patients are also eligible if they developed metastasis within a year after resection and then underwent resection, definitive radiation or ablation of solid, isolated, soft tissue metastases (excluding brain and bone lesions) with no evidence of active disease (M1NED). Patients will be randomized 1:1 to intravenous pembro for 48 weeks with or without the addition of tivo 1.34 mg by mouth daily D1-21 q28D for 6 months stratified by stage (T2T3 vs T4/N1 vs M1NED) . With no limit on dose holds or interruptions of tivo, dose reductions of tivo to 0.89 mg D1-21 q28D or tivo 0.89 mg every other day are allowed. No dose reductions of pembro are permitted. Following baseline imaging to confirm no disease, imaging is performed every 12 weeks for first year, every 16 weeks for second year, every 24 weeks for third year and then annually until 5 years after registration or progression. The primary endpoint will be disease-free survival (DFS) as assessed by investigator, with secondary endpoints being overall survival, safety and tolerability. The study will enroll 1040 patients to detect a minimum detectable hazard ratio of 0.67 (24-month DFS 84% in experimental arm) with 90% power. Quality of life analysis will compare global quality of life and fatigue between the two arms. Imaging and specimens will be banked for future research. The study opened to accrual in April 2025 and at this time 106 patients have enrolled. Clinical trial information: NCT06661720 .

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions for patients with prostate cancer across the disease spectrum. The Guidelines sections included in this article focus on metastatic castration-sensitive prostate cancer (mCSPC), nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). For patients with mCSPC, disease characteristics, such as whether metastases arose synchronously or metachronously and the degree of metastatic burden, impact therapy decisions, including how much treatment intensification is appropriate and when prostate-directed and/or metastasis-directed therapy should be considered. In the mCRPC setting, androgen deprivation therapy is continued with the sequential or concurrent addition of certain androgen receptor pathway inhibitors, 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, biomarkers, the extent and location of metastases, symptoms, and potential side effects.

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.

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.

Abstract Introduction Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. Methods Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score–matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. Results OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score–matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortality and number of lesions at CNS progression were similar for NSCLC and SCLC patients. Leptomeningeal progression was increased in patients with NSCLC compared to SCLC in the retrospective dataset only (multivariable hazard ratio = 1.61, 95% confidence interval = 1.14 to 2.26, P = .007). Conclusions After SRS, SCLC histology was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC patients overall but was similar in patients matched on baseline factors. SCLC was not associated with increased neurological mortality, number of lesions at CNS progression, or leptomeningeal progression compared to NSCLC. These findings may better inform clinical expectations and individualized decision making regarding SRS for SCLC patients.