Sheila Jonnatan

Adding a quick tag for the first author @jonnatansheila. Fantastic Research!

"Castration resistance" sounds like a simple loss of drug efficacy. The term might be completely misleading. Looking at the excellent new data from Sena et al. in The Prostate, we should probably start questioning some apodictic dogmas. 1/x

We may never be able to redo the TOAD trial, but this should at least give us some pause before assuming that early hormonal tx saves lives. Similar observational work: ascopubs.org/doi/abs/10.120… Congrats to @jonnatansheila & team for this practice-informing work! @PCF_Science

The brilliant @laurasenamd had a great thought experiment--if the process of developing CRPC (APMR?) accelerates growth kinetics, what would the implications be for optimal timing of systemic therapy in BCR/non-curative settings? onlinelibrary.wiley.com/doi/full/10.10… @Dr_RaviMadan

This project began as napkin doodles with the incredibly thoughtful @davidjeinstein and came to fruition through the dedication of @jonnatansheila. Many thanks to them and all coauthors and the pts. @Dr_RaviMadan @CathyHandy @MarkowskiGUOnc @EAntonarakis @PCF_Science @urotoday

This model should be validated experimentally, but underscores the need to recognize that surveillance remains a reasonable option for BCR, and future trials for BCR should include surveillance control arms. Please read the paper for more details!

To help conceptualize why this matters, we modeled the effect of castration @ BCR versus @ mets for a pt w accelerated progression with castration-resistance on OS. A key assumption is that depth and duration of response is independent of disease volume

This tells us that castration resistance is problematic not only due to fewer treatment options, but also due to a more rapid rate of progression.

We studied 40 pts from a unique cohort at Johns Hopkins who were monitored closely without tx for BCR, castrated at time of mets, and subsequently developed castration resistance. We found that castration-resistance was associated with >2-fold acceleration of disease kinetics

Trials have been inconclusive regarding benefit of castration for BCR vs waiting until mets, and recent studies such as EMBARK did not include a surveillance control arm. So whether tx for BCR prolongs survival compared to surveillance followed by tx for mets is not known.

While it is becoming trendy to start tx for advanced PCa @ BCR, earlier tx can mean earlier tx-resistance. We studied PCa kinetics longitudinally to find that CRPC is associated w disease acceleration, which has potential to shorten OS of pts w early tx 🧵 onlinelibrary.wiley.com/doi/full/10.10…

Today we accidentally dressed alike… the synergy in my new lab group is 🧨 @varshavakkala