Thank you. Agree, PSMA and PSA are just phenotypic markers that are demonstrably dispensable as mPC evolves under environmental and treatment selective pressure.

Thank you. Could you expand? PSA response vs PSMA response - is one better?

Still in the Dark… #PCWG4 launched #GU26 w/aspirational reliance on #PSMA imaging for drug development But we will have to acknowledge that #PSMA targeted therapy will likely impact the sensitivity of #PSMA imaging #PSMAdark @ascocancer.bsky.social @melissaabel20 et al rdcu.be/eKNQe

The #NCI past meets the present #GU26 @ascocancer.bsky.social Dr. Melissa Abel discusses emerging #PSMA tumor volume data with Dr. Harpreet Singh The emerging data is from a follow-up trial based on a trial Dr. Singh worked on during her time at the NCi

“Dry Mouth” remains a frequent toxicity w/#PSMA therapies #GU26; easy to discount which is why worth reviewing below There are no Grads 4/5 and grade 3 is TPN. Grade 2 is also no picnic for pts We need a better grading system & more data on reversibility #ProstateCancer @ascocancer.bsky.social

Dr. Fred Saad presents #Trillium 225Ac-PSMA in #mCRPC phase 1 study Substantial amount of dry mouth observed including 30% grade 2. @ascocancer.bsky.social #GU26

Dr. Fred Saad presents #Trillium 225Ac-PSMA in #mCRPC phase 1 study Substantial amount of dry mouth observed including 30% grade 2. @asco #GU26

Still in the Dark… #PCWG4 launched @ascocancer.bsky.social #GU26 w/aspirational reliance on #PSMA imaging for drug development But we will have to acknowledge that #PSMA targeted therapy will likely impact the sensitivity of #PSMA imaging #PSMAdark @melissaabel20 et al rdcu.be/eKNQe

Drs. Melissa Abel & Alexandra Sokolova chair the #GU26 chair this evening Rapid Abstract Presentations in #ProstateCancer @ascocancer.bsky.social

Poster A14 #GU26 @ascocancer.bsky.social One key bit of data missing in the context of #PSMA+ #BCR #ProstateCancer management in the wake of the #EMBARK data is how does #PSA Doubling Time interface w/ #PSMA Pet findings. Dr. Melissa Abel from #NCI will share this data today

PosterA4 #GU26 @ascocancer.bsky.social #BCR #ProstateCancer study @thenci 🩻PSMA➡️ 3 mos Enza💊➡️PSMA🩻 PSA control=days below baseline=clinical benefit🔵 PSA⬇️88-100%🟠 #PSMA Tumor Volume🟢 🚨PSMA-TV⬇️s/p Enza does NOT predict benefit These data in PSMA responders raise❓for adaptive designs

Oh I like this… #GU26

You’ve just beautifully summarised the vast majority of “🚨BREAKING NEWS! 🚨” papers and social media posts that come out of so many major meetings these days. We definitely need to do better. #GU26

🔜 #GU26 @ascocancer.bsky.social How to approach a vast meeting w/so much data? Look beyond data that repackages known truths but do NOT really advance understanding Common examples: 1. Less cancer is better than more cancer 2. Responders do better 3. More treatments vs. less improves PFS

🔜 #GU26 @ascocancer.bsky.social #ProstateCancer liver mets are lethal Finding at risk pts may be valuable “Using this unique approach we have identified a candidate gene signature for detection of LM in advanced PCa using platforms such as EV-based liquid biopsy. Further studies are underway…”

🔜 #GU26 @ascocancer.bsky.social “These findings… highlight the need for larger… studies to validate the prognostic value of PSMA-guided disease stratification & ensure its generalizability across diverse populations.” Agree!! Need more #PSMA data less presumption in #ProstateCancer

🔜 #GU26 @ascocancer.bsky.social Provocative early data “#Microplastics were found in tissue samples from 9/10 pts w/ #prostatecancer…w/greater concentration in tumor tissue compared to benign tissue. Additional research is in progress to study the link between MNPs w/prostate carcinogenesis.”

🔜 #GU26 @ascocancer.bsky.social “Detection of nodal and distant metastases below the Phoenix threshold challenges the current reliance on biochemical criteria to trigger imaging.” Contemporary ❓But does early #PSMA+ #BCR #ProstateCancer require tx? Probably not based on data from the NCI @ #GU26

🔜 #gu26 @ascocancer.bsky.social Would be good to see long term impact of ⬆️ PFS “The addition of #enzalutamide to standard ADT resulted in an improvement of PFS following SRT, warranting a phase 3 trial... and did not identify new safety concerns.” #ProstateCancer

🔜 #GU26 #ProstateCancer @ascocancer.bsky.social Important New trial guidance is valuable but important to distinguish from clinic practice recommendations “#PCWG4 expands guidance on patient & tumor profiling, as well as therapy development, to include both ADT sensitive & resistant settings…”

🔜 #GU26 @ascocancer.bsky.social Key to note IHC+ synaptophysin/chromogranin (seen in #ProstateCancer adenocarcinoma and small cell) alone should not exclude pts from Lu-PSMA Also highlights continue conflation of terms of #NEPC & small cell, the latter being truly virulent but also rare

🔜 #GU26 @ascocancer.bsky.social PFS benefit less than I would have expected… “The median (95% CI) PFS was 14.7 (11.7–21.3) mos among pts in the concomitant ARPI cohort vs 12.5 (11.5–13.6) months in the no concomitant therapy. Ongoing follow-up… on long-term clinical outcomes, including OS.”

With #GU26 approaching one key bit of data missing in the context of #PSMA+ #BCR #ProstateCancer management in the wake of the #EMBARK data is how does #PSA Doubling Time interface w/ #PSMA Pet findings. Dr. Melissa Abel @ the NCI will share this data @ #GU26 @ascocancer.bsky.social

It’s the story of a group of experts, who are bringing insights on the latest science... Announcing our lineup of experts who'll serve as #GU26 Featured Voices, sharing which abstracts they’re most interested in, putting the findings into context & taking you along for the journey.

Happy Holidays from your friends at the National Cancer Institute and NIH

Daily reminder: #PSMA doesn't show everything... 100 pts w/#BCR #ProstateCancer s/p previous PSMA radioguided surgery ▶️median PSA=0.9 ‼️91% recur@ median 11.4mos ‼️47%w/ distant recurrence beyond pelvis Important for pts to be aware of these data jnm.snmjournals.org/content/66/1...

What’s high risk #BCR #ProstateCancer? PSA DT:best predictive biomarker in BCR; required for BCR trials PSMA 🤷🏻‍♂️undefined role EMA says HR is <12 months EMBARK says <9 mos Per @NCI BCR WG the data is most c/w <6 mos (see sankey👇 of MFS with NO therapy) shorturl.at/HeEMh @ascocancer.bsky.social

🦃Happy Thanksgiving 🦃 A special shout out to all you #DallasCowboys  fans out there. (We all have a “complicated relationship”with this holiday 🤠)

👏🏼Interesting study #SBRT+/-#LuPSMA @ascocancer.bsky.social ⭐️Innovative design w/limited dosing of LuPSMA #oligorecurrent #ProstateCancer ❓What if all pts were MTD-Naive 🤔important differences in 🔑baseline characteristics favor combo 🤔PFS criteria w/❓clinical value ascopubs.org/doi/pdf/10.1...

Lots of ❓s in defining benefits of “#oligomet” or “#MDT” therapy in #ProstateCancer ❓ADT+/-ARPI? How long? ❓PFS vs Eugonadal PFS? ❓how many mets? Where? 🔑❓what imaging 🩻❓ #PSMA mets🚫🟰CT/Bone scan mets shorturl.at/n3JwU Std of Care? Or just something we can do?

We don’t need to fear the Dark in #ProstateCancer But we will have to acknowledge that #PSMA targeted therapy will likely impact the sensitivity of #PSMA imaging This likely impacts the desire to use PSMA in restating (still unclear how to do that) & drug development #PSMAdark

#PSMA+BCR That is how @theNCI #BCR Working Group unanimously agreed to define pts w/PSMA findings & neg CT/bone scan after definitive tx Retains all that is known about #BCR while drawing a distinction vs. mCSPC More than semantics for #ProstateCancer pts & clinicians @ascocancer.bsky.social

#EMBARK #BCR📈 #ProstateCancer I have a forrest plot ? 2 subgroups w/LACK of clear benefit are⬆️CV risk(competing mortality-logical) But why would pts under⬇️65 not🚫 have clear benefit? This is a subgp where competing mortality shouldn’t be an issue & Tx should help ⁉️🧐

As #ESMO25 brings new data on #PSMA it may be time to consider what happens when you target a surface antigen in cancer. How will that impact diagnostic sensitivity of that target? #PSMAdark #ProstateCancer #theranostics Dr Abel et al @natrevurol.nature.com @ascocancer.bsky.social rdcu.be/eKNQe

#EMBARK #ESMO25 creates the need to risk stratify pts Here is data published last year which demonstrates that #ProstateCancer specific death is rare among unselected #BCR pts. EMBARK Tx is for high risk pts (eg PSA DT<6mos) tinyurl.com/y69hb5ue

Lots @ #ESMO25 re: #BCR #ProstateCancer but over-treatment of this indolent disease remains an important issue How does #PSMA imaging factor in? See poster #2393P presented by @HelenMoonMD Saturday +PSMA findings in BCR pts shouldn’t be the reason to treat as rPD is rare @1yr

As #ESMO25 brings new data on #PSMA it may be time to consider what happens when you target a surface antigen in cancer. How will that impact diagnostic sensitivity of that target? #PSMAdark #ProstateCancer #theranostics Dr Abel et al @natrevurol.nature.com @ascocancer.bsky.social rdcu.be/eKNQe

From The NCI #PSMA files 73 yo male PSA=17 PSADT=11.6mos PSMA=5+ nodes in pelvis RP & torso (All~5mm). Neg CT and bone scan No🚫Treatment 1 yr later PSA=40 PSADT=13.1 mos PSMA stable across 2 scans over 12 mos #PSMA+ #BCR #ProstateCancer is an indolent process-OK to monitor these pts

Important to distinguish #serosal findings on #PSMA 🩻vs. #parenchymal Serosal lesions are better seen on #PSMA vs CT/MRI in #ProstateCancer but likely have an indolent course even with no 🚫therapy (even on the liver!) Dr. Melissa Abel at el @natrevurol.nature.com rdcu.be/eBwPs

Restaging w/ #PSMA Imaging in #mCRPC #ProstateCancer: When Seeing More Is Detrimental to Care Sadly a year later this remains true & the frequency of this is 📈 @ascocancer.bsky.social @ascopost.bsky.social ascopubs.org/doi/pdf/10.1...

We have known for more than 20 years that chemotherapy has clinically significant efficacy in metastatic #ProstateCancer #pcsm, including improved overall survival. It has not stopped working just because new agents are available or are being tested.

Two opinions that to my surprise are either unpopular or not widely held: 1. The control arm of a randomised trial should be best standard of care. 2. A PFS benefit against an inactive comparator is not a major advance, if progressive disease is required for eligibility.

Pleasure to highlight your work with #UroToday @ravimadan.bsky.social - as we all consider how best to treat PSMA avid disease.

Do #PSMA+ findings in #BCR #ProstateCancer require immediate treatment? NO based on emerging data @theNCI Appreciate @tiansterzhangmd.bsky.social & #Urotoday for the opportunity to discuss Ongoing trial of PSMA scans in BCR is still enrolling shorturl.at/36nGQ www.urotoday.com/categories-m...

Great discussions #ProstateCancer posters #ASCO25 @ascocancer.bsky.social #PSMA+ #BCR is indolent & pts do NOT require urgent therapy in most cases We should be ⚠️ cautious about over-treatment 🔗shorturl.at/NtxdF Trial continues to accrue @theNCI www.clinicaltrials.gov/study/NCT055...

Most expected #Arches 5 yr follow up data to be pro-forma #ASCO25 @ascocancer.bsky.social But then this data popped up 👀 Less clear benefit of Enza+ADT in low volume #mCSPC Should this raise ?s for #mCSPC intensification w/#parp & #LU-psma Implications for over treating PSMA+ recurrence?

It remains disappointing that (unlike the Lu-PSMA trials) the #PARP inhibitor trials do not include cross over and thus continue to leave the key question of sequence unanswered. This limits understanding of clinical optimization #AMPLITUDE #ASCO25 @ascocancer.bsky.social

How to discern important new data @ ASCO? Look beyond data that repackages known truths but do NOT really advance our understanding Common examples: 1. Less cancer is better than more cancer 2. Responders do better 3. More treatments vs. less improve PFS Happy #ASCO25 @ascocancer.bsky.social

Around this time of year we see the “How should #oncology #fellows navigate the ASCO mtg?” advice. My take: 👉🏽Very Carefully 🤓 Distinguish science from showmanship and make sure the substance of a presentation aligns with the “take home message” Happy ASCO ☺️ @ascocancer.bsky.social #ASCO25