ESMO Congress 2026

Stop by our booth to discover how we are leveraging AI-enabled technologies to advance precision medicine.

Early-onset prostate cancer (EO-PCa) is increasingly recognized as biologically distinct, but its clinical behavior, molecular features and outcomes relative to late-onset disease (LO-PCa) are incompletely characterized. Using the Tempus Lens Platform, the team queried the de-identified multimodal database for 6,967 metastatic prostate cancer patients tested with Tempus xT (DNA-seq) and xR (RNA-seq), stratified by onset age (EO-PCa <=55 years). EO-PCa made up 8.4% of cases, was more common in Black than white patients, had higher median PSA, and was enriched for germline BRCA2 variants and TMPRSS2/ERG fusions, while LO-PCa had more FOXA1 and SPOP mutations. EO-PCa was associated with longer median survival (42 vs 32 months), with SPOP alterations prognostic for favorable and TP53 alterations for worse survival.

PTEN alterations confer aggressive prostate cancer biology, but PI3K-AKT pathway targeting has yielded inconsistent results and prior studies did not account for alteration subtype, PI3K burden, or molecular lineage. Using the Tempus Lens platform, de-identified real-world data from 4,853 metastatic androgen pathway modulation sensitive (mAPMS) patients treated with 1L ADT-based therapy were analyzed with Tempus xT/xR NGS (DNA & RNA), assessing variants includingPTEN and ERG fusions. PTEN alteration alone was not prognostic; effects were context-dependent, emerging only in ERG-negative tumors, where PTEN deletion and higher PI3K pathway alteration burden were each associated with worse overallsurvival. The authors conclude comprehensive NGS can identify a high-risk subgroup and refine patient selection for treatment intensification in trials.

The mechanisms underlying survival differences between de novo and metachronous metastatic prostate cancer (mPC) are incompletely characterized. The Tempus Lens Platform was used to query the de-identified multimodal database for 6,306 mPC patients tested with Tempus xT (DNA-seq) and xR (RNA-seq), comparing clinicogenomic features and RNA-derived immune composition (quanTIseq). Metachronous patients were younger with lower PSA at diagnosis, more prior local therapy (prostatectomy/radiation), and enrichment for APLNR and ZMYM3 alterations, while canonical drivers (TP53, PTEN, ERG) were similar between groups. They also showed increased regulatory T-cell and NK-cell infiltration and enriched inflammatory (TNFa/NF-kB) signaling, indicating a more immunologically active tumor microenvironment.

TP53 is the most frequently mutated tumor suppressor gene in solid tumors, and Y220C is a targetable hotspot mutation of growing therapeutic interest. A retrospective analysis of 200,391 de-identified solid-tumor samples was performed using the Tempus Lens Platform, classifying tumors as TP53 wild-type or Y220C and assessing prevalence, co-alterations, HRD status and real-world overall survival (rwOS). TP53-Y220C was detected in 0.9% of tumors (highest in ovarian, 3%), frequently co-occurring with KRAS and CDKN2A, and carried shorter rwOS than TP53 wild-type. Survival was significantly worse in ovarian, uterine and pancreatic cancers, defining a genomically and clinically distinct pan-cancer subgroup.

Early-onset breast cancer (EOBC; <=45 years) is a growing public health challenge and the leading cause of cancer death in young women, yet outcomes remain worse than in later-onset disease. Women with invasive breast cancer and Tempus xT NGS (DNA, 648 genes) were retrospectively identified from the Tempus Lens database, and somatic variants and copy-number changes were compared across age groups. Of 17,129 patients, 20.6% were EOBC; they were enriched for HER2-positive disease, more advanced stage at diagnosis, and higher frequencies of TP53, BRCA1/2 and GATA3 mutations. PIK3CA (an actionable target) and CDH1 were less prevalent in EOBC, while ERBB2, FGFR-pathway and cell-cycle gene amplifications were enriched, pointing to a distinct clinical and genomic profile.

The PD-L1 combined positive score (CPS) is a widely used but imperfect biomarker in head and neck squamous cell carcinoma (HNSCC), motivating a more nuanced alternative. The team analyzed de-identified records of 2,121 HNSCC cases from the Tempus database with whole-transcriptome RNA sequencing (Tempus xR), applying Tempus' AI-developed Immune Profile Score (IPS) plus unsupervised clustering to define transcriptomic immune archetypes. Two archetypes emerged: a small "Inflamed" group (n=243) and a large "Immune-Desert" group (n=1,878), with the Inflamed group enriched for IPS-High, HPV16-positivity and CPS>=1 and showing markedly longer median real-world overall survival (25.1 vs 16.8 months). IPS-High, HPV16-positivity and CPS>=1 were each confirmed as independent prognostic factors for improved survival.

Timely identification of actionable biomarkers improves NSCLC outcomes, but guideline-recommended NGS and IHC testing rates remain low, so rapid pre-screening of routine slides at diagnosis could improve follow-through testing and access. A machine-learning pre-screening panel (Tempus with Paige and Pfizer) was developed to predict 12 clinically relevant biomarkers from H&E whole-slide images, trained on multimodal DNA sequencing (MSK-IMPACT or Tempus xT) and IHC across 60,459 cases from 56,969 patients. In the holdout set, the panel achieved sensitivity above 80% for all target biomarkers and above 90% for some rare events such as ALK fusion. These results validate the assay for pre-screening use in NSCLC.

ATM germline mutation carriers have a two-fold increased risk of ovarian cancer, but little is known about the tumor biology and outcomes of ATM-associated ovarian cancer. Using the Tempus Lens Platform, ovarian cancer patients tested with Tempus xT (DNA, 648 genes) and tumor-normal matched testing who received 1L platinum-based therapy were identified, comparing somatic alterations and real-world progression-free survival (rwPFS) between carriers and non-carriers. Among 1,810 patients (314 carriers, including 37 ATM), ATM carriers had fewer somatic TP53 alterations (37.8% vs 79.0%) and a trend toward more KRAS alterations, and BRCA1 carriers had longer rwPFS than ATM carriers while ATM and non-carriers did not differ. Despite fewer TP53 mutations, ATM-associated ovarian cancers had shorter PFS than BRCA1/2-associated disease, suggesting a biologically distinct entity with implications for trial design and prevention.

VEGF family signaling shapes angiogenesis and immune regulation in NSCLC, but ligand- and isoform-specific effects on (chemo)immunotherapy (IO) outcomes remain unclear. Tempus clinicogenomic data (2011-2025) were evaluated for metastatic NSCLC patients on frontline chemoIO, IO, or chemo, assessing VEGF ligand, receptor and splice-isoform expression against real-world PFS and OS using multivariable Cox models and tumor-microenvironment deconvolution. Across 2,852 cases, VEGF family members showed opposing prognostic patterns: higher VEGF-C, VEGF-A-165 and FLT4-long were linked to inferior survival, while VEGF-B and VEGF-A-121 were associated with improved outcomes, with up to 4.8-month differences in survival. VEGF-C expression strongly correlated with cancer-associated fibroblast enrichment, supporting a stromal-driven immunosuppressive mechanism.

Trastuzumab deruxtecan (T-DXd) has tumor-agnostic approval for HER2-expressing tumors and rapid uptake in gynecologic cancers, but real-world data remain limited. The team used the Tempus Lens platform to identify 81 patients with gynecologic malignancies treated with T-DXd who had clinical sequencing with the Tempus xT (DNA) and/or xR (RNA) assays, evaluating real-world progression-free survival (rwPFS) stratified by HER2 IHC. Median rwPFS was 7.1 months overall (6.5 months in ovarian, 8.6 months in endometrial cancer), with a trend toward longer rwPFS at higher HER2 expression (13.9 months in IHC 3+ vs 7.4 months in IHC 2+). In multivariable analysis, only HER2 IHC 2+ (vs 3+) was associated with worse outcomes.

GCN2 (EIF2AK4), an amino-acid stress-sensing kinase, is essential for growth in prostate cancer models, but the significance of its expression in advanced prostate cancer (PCa) is unclear. The Tempus Lens Platform was used to query the de-identified multimodal database for metastatic PCa patients with Tempus xT (DNA, 648 genes) and xR (whole-transcriptome RNA) testing, dividing GCN2 expression into tertiles (low/mid/high). Among 8,456 patients, high GCN2 correlated with fewer castration-resistant and more hormone-sensitive cases and more primary-tumor samples, while low GCN2 tumors were enriched for high-risk alterations such as TP53. Overall, higher GCN2 expression was associated with more favorable clinical and genomic features in advanced prostate cancer.

Clear-cell renal cell carcinoma (ccRCC) is characterized by VHL loss, hypoxia signaling and metabolic stress, with the integrated stress response active in the disease, prompting study of GCN2 expression. The de-identified Tempus multimodal database was queried via the Lens Platform for metastatic RCC patients with Tempus xT (DNA, 648 genes) and xR (whole-transcriptome RNA) testing, stratified into GCN2 expression tertiles with immune fractions estimated by quanTIseq. Among 2,097 patients, high GCN2 was enriched for PBRM1 mutations, depleted of adverse alterations (BAP1, CDKN2A/B, MTAP), and immunologically "cold," but was not significantly associated with real-world overall survival or time to next treatment. The findings support GCN2 as a biologically relevant therapeutic axis, with pharmacologic activation already being explored clinically in ccRCC (NCT06234605).