Table 2:

Priorities to accelerate precision medicine in metastatic prostate cancer

Challenges	Short Term Goals	Longer Term Goals
Challenge 1: Access to tumor tissue for molecular profiling	Standardization of protocols for the collection and processing of specimens for genomic profiling Partnership between oncologists, radiologists, and pathologists regarding optimal techniques and team education Incorporation of sample processing protocols for future molecular tests (eg., RNA, protein)	Functional imaging to improve diagnosis and biopsy acquisition Generation of patient-derived prostate cancer models for precision medicine ex-vivo clinical trials.
Challenge 2: Addressing tumor heterogeneity	Expanded correlation of liquid biopsies and molecular imaging with single site tumor biopsies at different stages of the disease and under distinct therapeutic contexts Optimization of ctDNA, CTC, and other liquid biopsy approaches to improve sensitivity to detect common prostate cancer alterations in the circulation including copy number aberrations Implementation of approaches to capture tumor microenvironment, including immune infiltrates, at different disease states	Integration of multi-omic approaches (eg., genomics with transcriptomics and protein-based functional assays) to provide additional readouts of pathway activation/suppression. Utilization of functional imaging and liquid biopsies to identify early acquired resistance Improved understanding of the intersection between tumor genomics and tumor-immune system regulation
Challenge 3: Detection of complex drivers	Clinical characterization of not only single gene aberrations, including rare long tail events, but also how co-occurring alterations modulate the predictive value for a biomarker-drug matches Functional characterization of rare /uncommon molecular alterations and co-occurring lesions in preclinical models	Understanding mechanisms of response and resistance to therapies Drug discovery for targeting rare aberrations Clinical-grade tests beyond targeted genomic panels, such as WGS, transcriptomics, methylation Precision oncology trials focused on gene expression signatures, metabolism, epigenetics, or other non-genomic features
Challenge 4: Clinical and genomic integration	Streamline of consent process to facilitate broader sharing of de-identified data Generation of a prostate cancer specific N=1 database collecting and linking genomic and clinical data from academic and community partners Institutional or supra-institutional protocols collecting tumor and liquid biopsies for later evaluation of exceptional responders and exceptional non-responders as well as acquired resistance	Harmonization of genomics data coming from different tests for uniform /comparable annotations, reporting, and visualization Machine-learning approaches to integrate emerging data for genomics-clinical outcome correlations, validation of complex algorithms to prioritize choices of therapies or clinical trials Developing paradigms for precision oncology based on specific alterations
Challenge 5: Understanding the impact of genomics in diverse patient populations.	Partnership with patients, community providers, local health departments, the Veterans administration, and other stakeholders Improving access to somatic and germline sequencing for all men with advanced prostate cancer, including underserved populations Point of care educational resources for physicians and patients New technologies and social media platforms to facilitate partnerships with patients and advocacy groups throughout the process Provide access of N=1 database to patients/providers beyond academic institutions	Genomic landscape studies focused on previously underrepresented populations Improved understanding regarding how germline genetics impacts tumor somatic genomic profiles and tumor phenotypes Elucidation of the interaction between genomic, environmental and lifestyle factors for determining tumor progression and response to therapy Long term impact on reducing disparities
Challenge 6: Access to matched therapies and clinical trials	Decision support and education materials for practitioners and patients Live and virtual prostate cancer molecular tumor boards to support clinical decision making Matching of patients with molecularly-defined clinical trials and therapies (eg., via MatchMiner)	Development of a prostate cancer umbrella protocol for research testing of a platform of agents in molecularly selected populations Early phase trials testing novel molecularly targeted and immune based therapeutic targets and drugs Repurposing of available drugs for molecularly selected populations (“off-label clinical trials”) Development of consensus guidelines for stakeholders (insurance companies, health systems) on off-label use Streamlining N=1 Investigational New Drug processes for compassionate use of unapproved agents