NADIR Model: A Prognostic Framework for Early Treatment Stratification in mHSPC

Doctors treating advanced prostate cancer start patients on hormone therapy plus a drug called an androgen receptor pathway inhibitor, or ARPI. These drugs work well for most men, but doctors must wait six months to check if the PSA blood level drops very low, to 0.2 nanograms per milliliter or less. This low PSA strongly predicts long response. But waiting six months can be risky. Cancer might grow during that time, making it harder to treat later.

Current ways to guess risk, like measuring tumor size or spread, do not work well enough. Half of low-risk patients still have large tumors. No tool existed before treatment to predict who would get this good PSA drop early on.

A new study, published on Nature, created a simple math tool called the NADIR model to solve this. It uses data from four big trials: LATITUDE, TITAN, ARASENS, and ENZAMET. These tested three ARPIs (abiraterone, apalutamide, and darolutamide) plus enzalutamide. The model uses easy-to-get facts from the start of treatment: PSA level, blood count for red cells, body weight and height, age, tumor size group, if cancer spread to organs, and if it was new cancer or came back. The tool predicts the chance of hitting PSA 0.2 or lower by six months.

They tested it on thousands of men. First, data from LATITUDE, TITAN, and ARASENS arms went into training and checking groups. Then ENZAMET provided outside testing. The tool split patients into three equal groups by predicted chance. In the best group, 92 percent hit the low PSA. In the worst group, only 39 percent did. The tool was accurate at matching predictions to real results.

This prediction seems to link directly to life expectancy. Men in the best group had 80 percent survival at four years. Men in the worst group had 56 percent, a 24 percent gap. This means doctors can act sooner. Poor responders might get extra drugs right away, like more chemo, before cancer worsens. Good responders might later try less treatment once confirmed.

The tool does not replace checking PSA over time. It adds early clues for choices. An online calculator makes it free and simple for any doctor or patient. Anyone can enter their starting facts and see their predicted chance.

Source.