Palma, David A.

160 Background: To our knowledge, no tools are available to guide care in oligometastatic prostate cancer (omPC). Here, we leveraged individual patient-level data pooled from 8 randomized trials in the X-Met collaboration to construct CEREBRO, a tool for predicting patient-specific responses to various treatment scenarios. Methods: Patients with omPC from the STOMP, ORIOLE, SABR COMET, EXTEND continuous ADT, EXTEND intermittent ADT, ARTO, RADIOSA, and RAVENS trials were included. 6 patients (1%) with missing data were excluded. Treatment scenarios were defined as active surveillance (AS), metastasis-directed therapy (MDT), systemic therapy (ST), or MDT+ST. To account for varying baseline hazards, Weibull models were fit for overall survival (OS); progression-free survival (PFS); and castration-resistance free survival (CRFS) for patients with hormone-sensitive disease. Endpoint definitions were harmonized per X-Met framework. Results: Of 600 patients included (treatment scenarios: AS=50; MDT=153; ST=172; MDT+ST=225), 405 (67%) had hormone-sensitive omPC. With median follow-up of 38 months, median PFS, CRFS, and OS of all patients were 18, 70, and 84 months. In order of relative contribution, inputs for predicting outcomes were: treatment scenario, stage, prostate-specific antigen annotated by ADT status, metachronous vs synchronous presentation, imaging type, number of metastases, hormone sensitivity, and age. The model for each endpoint showed robust fit, calibration, superiority against the null model (per the likelihood ratio test), and risk stratification (Table). Median PFS times for model-defined low-, intermediate-, and high-risk strata were 46 months, 18 months, and 7 months ( p <0.0001). In addition, the PFS and OS models also showed strong discrimination via c index and a large interval of risk probabilities with additive clinical utility per decision-curve analysis (Table). A public webpage will be made available to facilitate prospective trial stratification, patient counseling for patient-specific outcome predictions for each potential treatment scenario, and forecasts comparing outcomes between treatment scenarios. Conclusions: CEREBRO is a high-performance tool, trained on robust prospective data from 8 randomized trials with routinely collected clinical variables, for predicting risk and treatment outcomes in omPC. Given the uncertainties in optimal timing of MDT and combination with ST, this tool has been built to facilitate current decision making. External validation is planned. Model summary. Endpoint C index (95% CI) Calibration Likelihood ratio p Risk strata p Net clinical utility observed between thresholds PFS 0.72 (0.70-0.75) 1.04 <0.0001 <0.0001 0.2-1.0 CRFS 0.63 (0.60-0.70) 1.01 0.02 0.004 0.2-0.5 OS 0.81 (0.76-0.86) 1.01 <0.0001 <0.0001 0.05-1.0

The treatment of patients with HPV-associated oropharyngeal cancer (HPV-OPC) is rapidly evolving and challenging the standard of care of definitive radiotherapy with concurrent cisplatin. There are numerous promising de-escalation strategies under investigation, including deintensified definitive chemoradiotherapy, transoral surgery followed by de-escalated adjuvant therapy, and induction chemotherapy followed by de-escalated locoregional therapy. Definitive radiotherapy alone or with cetuximab is not recommended for curative-intent treatment of patients with locally advanced HPV-OPC. The results of ongoing phase III studies are awaited to help answer key questions and address ongoing controversies to transform the treatment of patients with HPV-OPC. Strategies for de-escalation under investigation include the incorporation of immunotherapy and the use of novel biomarkers for patient selection for de-escalation.