Muscle-invasive bladder cancer (MIBC) can be divided into six molecular classes that may eventually guide clinical decision making, according to an international consensus group.
The six classes are based on a variety of disease factors, including immune and stromal cell infiltration, oncogenic mechanisms, histologic features, and clinical characteristics, reported lead author Aurélie Kamoun, PhD, of Ligue Nationale Contre le Cancer in Paris, and colleagues.
Although several molecular classification systems for MIBC have been previously published, subtypes have varied widely, the investigators explained in European Urology.
“This diversity has impeded transferring subtypes into clinical practice and highlights that establishing a single consensus set of molecular subtypes would facilitate achieving such a transfer,” the investigators wrote.
In order to reach a consensus, the investigators drew data from the six previously published classification systems, including 1,750 transcriptomic profiles from 16 published datasets and 2 additional patient populations.
Using a network-based approach, the investigators identified consensus classes that reconciled differences between the previously published systems. This process revealed a core set of 1,084 consensus samples, from which the investigators built a single-sample transcriptomic classifier. This free tool is now available online at https://github.com/cit-bioinfo/consensusMIBC.
The six consensus molecular classes (with prevalence among samples) are basal/squamous (35%), luminal papillary (24%), luminal unstable (15%), luminal nonspecified (8%), stroma rich (15%), and neuroendocrine like (3%).
The investigators described a number of disease characteristics that correlate with each molecular class, from the genomic to the clinical level. For example, basal/squamous tumors were associated with TP53 mutations and immune infiltration involving natural killer cells and cytotoxic lymphocytes.
Similar conclusions were described at the clinical level.
Consensus class predicted overall survival, with neuroendocrine-like tumors having the worst prognosis relative to luminal papillary tumors (hazard ratio, 2.34; P less than .03).
The investigators also highlighted some possible treatment implications related to subtype. For example, patients with basal/squamous or luminal nonspecified tumors derived benefit from neoadjuvant chemotherapy. Similarly, patients with luminal nonspecified, luminal unstable, or neuroendocrine-like tumors were more likely to respond when given atezolizumab.
“We expect that this consensus classification will help the development of MIBC precision medicine by providing a robust framework to connect clinical findings to molecular contexts and to identify clinically relevant biomarkers for patient management,” Dr. Kamoun and coauthors concluded.
The investigators reported relationships with Bayer, Astellas, Genentech, and others.
SOURCE: Kamoun A et al. Eur Urol. 2019 Sep 26. doi: 10.1016/j.eururo.2019.09.006.