Jama Oncology最新文献

Importance: The magnetic resonance imaging (MRI) pathway for diagnosing clinically significant prostate cancer (csPCa; defined as International Society of Urological Pathology grade group ≥2) uses multiparametric MRI (mpMRI) for prostate biopsy (PB) decision-making. However, the intermediate impact on patient outcomes in men with negative MRI results avoiding PB and men with positive MRI results without PCa remains unknown.

Objective: To assess the feasibility and safety of a community-based MRI diagnostic strategy in men with suspected PCa using 3-year active monitoring.

Design, setting, and participants: This multisite, longitudinal cohort trial took place across 54 community-based urology practices and 2 radiology imaging centers at a referral academic institution in Berlin, Germany. Eligible participants aged 18 to 75 years with clinically suspected PCa were enrolled between September 2016 and December 2017 and monitored for 3 years. Final analysis was reported on December 23, 2023.

Exposures: Participants underwent 3-T mpMRI. Men with findings suspected to be PCa were recommended for targeted PB (diagnostic phase). Men with negative mpMRI results or positive mpMRI results with benign findings at PB were systematically monitored for 3 years (monitoring phase). Clinical visits were recommended every 6 months.

Main outcomes and measures: The total proportion of men avoiding PB and those with csPCa.

Results: A total of 593 men (median [IQR] age, 64 [58-70] years) underwent mpMRI, with 286 (48%) having negative MRI results, 261 (44%) avoiding PB initially, and 242 (41%) avoiding PB over 3 years. csPCa was detected in 161 (27%) men after immediate PB, increasing to 172 (29%) men after 3 years. Seven men with negative MRI results were diagnosed with PCa by immediate PB (including 4 cases of csPCa), while 279 entered monitoring. Three-year monitoring was completed by 233 (84%) men, with 7 diagnoses of csPCa. Of 307 men with positive MRI results, 58 (19%) showed no PCa after immediate PB, of which 41 (71%) completed monitoring and 4 (7%) were diagnosed with csPCa.

Conclusions and relevance: In this cohort study, men with negative mpMRI results avoiding biopsy were not at elevated risk of csPCa. The study confirms the oncological safety of the prebiopsy MRI strategy of avoiding an immediate PB after negative MRI results when a programmatic safety net is in place.

Importance: Active monitoring (AM) for low-risk ductal carcinoma in situ (DCIS) has been considered as a potential alternative to guideline-concordant care (GCC; inclusive of surgery with or without radiation). Reported data comparing patient-reported outcomes (PROs) between GCC and AM for DCIS are lacking.

Objective: To compare PROs at baseline and over time in patients with low-risk DCIS randomized to receive either AM or GCC.

Design, setting, and participants: This prespecified secondary outcome analysis used prospectively collected validated questionnaires at baseline, 6 months, 1 year, and 2 years from participants enrolled from June 2017 to January 2023 in the Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) study for low-risk DCIS, which randomized participants to receive GCC or AM.

Intervention: Randomization to GCC or AM.

Main outcomes and measures: Context-relevant PROs, including health-related quality of life, anxiety, depression, and symptoms measured by validated survey instruments. Mixed models, including sensitivity analyses, with group, point, and group-by-point effects were used to compare PROs between groups.

Results: Of the 957 participants in COMET, 225 (24%) were younger than 55 years at enrollment, 325 (34%) were aged 55 to 65 years, and 403 (42%) were older than 65 years, and 953 (99.5%) completed questionnaires at some point within the first 2 years, with a completion rate of more than 83% at all points. Quality of life, anxiety, depression, worries about DCIS, and symptom trajectories were comparable between groups, with modest fluctuations over time of limited clinical significance. Physical functioning was the only specific Medical Outcomes Study 36-item short-form health survey (SF-36) domain for which changes in the score trajectory differed by group over time, with mean scores ranging from 50 (baseline) to 48 (6, 12, and 24 months) in the GCC group and 50 (baseline) to 47 (12 months) and 48 (6 and 24 months) in the AM group (pooled SD, 9.9; P = .01), although these were also of limited clinical significance.

Conclusions and relevance: In this prespecified secondary analysis of the COMET prospective randomized trial, the overall lived experience of women randomized to undergo AM for low-risk DCIS was similar to that of women randomized to GCC during the 2 years following diagnosis.

Trial registration: ClinicalTrials.gov Identifier: NCT02926911.

Importance: Evidence-based treatment decisions for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) require individualized patient-centered decision-making that accounts for patient and cancer characteristics.

Objective: To create an accessible guidance document to educate clinicians and patients on biomarkers informing prognosis and treatment in unresectable or metastatic GEP-NENs.

Methods: A multidisciplinary panel in-person workshop was convened to define methods. English language articles published from January 2016 to January 2023 in PubMed (MEDLINE) and relevant conference abstracts were reviewed to investigate prognostic and treatment-informing features in unresectable or metastatic GEP-NENs. Data from included studies were used to form evidence-based recommendations. Quality of evidence and strength of recommendations were determined using the Grading of Recommendations, Assessment, Development and Evaluations framework. Consensus was reached via electronic survey following a modified Delphi method.

Findings: A total of 131 publications were identified, including 8 systematic reviews and meta-analyses, 6 randomized clinical trials, 29 prospective studies, and 88 retrospective cohort studies. After 2 rounds of surveys, 24 recommendations and 5 good clinical practice statements were developed, with full consensus among panelists. Recommendations focused on tumor and functional imaging characteristics, blood-based biomarkers, and carcinoid heart disease. A single strong recommendation was made for symptomatic carcinoid syndrome informing treatment in midgut neuroendocrine tumors. Conditional recommendations were made to use grade, morphology, primary site, and urinary 5-hydroxyindoleacetic levels to inform treatment. The guidance document was endorsed by the Commonwealth Neuroendocrine Tumour Collaboration and the North American Neuroendocrine Tumor Society.

Conclusions and relevance: The study results suggest that select factors have sufficient evidence to inform care in GEP-NENs, but the evidence for most biomarkers is weak. This article may help guide management and identify gaps for future research to advance personalized medicine and improve outcomes for patients with GEP-NENs.

Importance: The prognosis for patients with glioblastoma is poor following standard therapy with surgical resection, radiation, temozolomide, and tumor-treating fields.

Objectives: To evaluate the combination of veliparib and temozolomide in glioblastoma based on preclinical data demonstrating significant chemosensitizing effects of the polyadenosine diphosphate-ribose polymerase 1/2 inhibitor veliparib when combined with temozolomide.

Design, setting, and participants: Patients with newly diagnosed glioblastoma with MGMT promoter hypermethylation who had completed concomitant radiation and temozolomide were enrolled between December 15, 2014, and December 15, 2018, in this Alliance for Clinical Trials in Oncology trial. The data for this analysis were locked on April 21, 2023.

Interventions: Patients were randomized and treated with standard adjuvant temozolomide (150-200 mg/m2 orally, days 1-5) combined with either placebo or veliparib (40 mg orally, twice daily, days 1-7) for 6 cycles.

Main outcomes and measures: The primary end point for the phase 3 portion of the trial was overall survival (OS).

Results: There were 322 patients randomized during the phase 2 accrual period and an additional 125 patients randomized to complete the phase 3 accrual, for a total of 447 patients in the final phase 3 analysis. The median (range) age for patients was 60 (20-85) years and 190 patients (42.5%) were female. The median OS was 24.8 months (90% CI, 22.6-27.7) for the placebo arm and 28.1 months (90% CI, 24.3-33.3) for the veliparib arm (P = .17). The difference in survival did not meet the prespecified efficacy end point. However, there was a separation of the survival curves that favored the veliparib arm over 24 to 48 months of follow-up. The experimental combination was well tolerated with an acceptable elevation in grade 3 or 4 hematologic toxic effects.

Conclusions and relevance: This trial found that adding veliparib to adjuvant temozolomide did not significantly extend OS in patients with newly diagnosed, MGMT-hypermethylated glioblastoma.

Trial registration: ClinicalTrials.gov Identifier: NCT02152982.

Importance: Evidence on prostate cancer (PCa) in transgender women is very limited; data are needed to reduce gender disparities in both PCa knowledge and health care.

Objective: To evaluate the prevalence of PCa among transgender women in the US and assess the factors associated with PCa, and factors associated with biochemical recurrence (BCR) and bone metastases (BM) secondary to PCa in the transgender population.

Design, setting, and participants: A retrospective cohort study was conducted in October 2023, covering the period between 2011 and 2022 (12-year analysis). The study was based on a large, all-payer claims, deidentified, US database (PearlDiver Mariner). Transgender women who were identified as male before assignment of transsexual status codes were included. Patients with PCa were detected in the transgender women population.

Main outcomes and measures: PCa diagnosis was selected as primary outcome; BCR and BM were chosen as secondary outcomes.

Results: A total of 95 460 transgender women with a mean (SD) age of 52.5 (9.4) years were included. PCa was diagnosed in 589 individuals with a mean (SD) age of 66.8 (10.0) years (estimated prevalence, 0.62%; 95% CI, 0.54%-0.77%). Age (adjusted odds ratio [OR], 1.10; 95% CI, 1.08-1.12; P < .001) and family history (adjusted OR, 2.27; 95% CI, 1.60-4.92; P < .001) were positively associated with PCa in transgender women. Gender-affirming hormone therapy (GAHT) was negatively associated with PCa in transgender women (OR, 0.60; 95% CI, 0.56-0.89; P < .001) but positively associated with BCR (OR, 1.83; 95% CI, 1.21-2.86; P < .001) and BM (OR, 3.96; 95% CI, 1.50-9.99; P < .001) in the transgender population with PCa.

Conclusions and relevance: This cohort study found that PCa appeared to be relatively uncommon in transgender women. GAHT may reduce the risk of PCa in transgender patients, but it may also increase the risk of BCR and BM in transgender women with PCa. Further studies are needed to confirm our findings.