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

Rorschach Test for #ProstateCancer in 2025 Treat w/your favorite approach +/- your 2nd favorite approach? Or acknowledge lack of data supporting long term benefits in this case & defer tx? @theNCI continues to enroll #BCR pts on #PSMA monitoring trial www.clinicaltrials.gov/study/NCT055...

Case from the #NCI #PSMA files 67 yo w/#BCR #ProstateCancer 4 yrs s/p RP (declined salvage) PSA=1.0 PSA DT=11 mos(“high risk”per European criteria) PSMA shows only 6 mm obturator node next to ureter (SUVmax=26) —no treatment 18 months later PSA is 1.1 LN=8mm No new findings on PSMA

Do these clinical trial failures demonstrate a failure of traditional pre-clinical models to reflect the human disease? In addition to the complete avoidance of biomarker-driven clinical trials to find the subset of patients that would benefit.? @asharpmedonc.bsky.social @pcf-science.bsky.social

Dr. Susan Slovin from MSK asks some key questions regarding #ProstateCancer #Immunotherapy @ascocancer.bsky.social ascopubs.org/doi/10.1200/...

3 consults this wk. PSA 1 or well below with no significant change. On ADT+ARPI, w/recommendation for chemo based on #PSMA “changes”. Rapidly discarding #ProstateCancer therapies likely is harming pts @ascocancer.bsky.social @pcf-science.bsky.social ascopubs.org/doi/10.1200/...

Our new paper in JITC with a group of fine international friends, mentees and colleagues about immunotherapy in patients with cardiac metastasis. jitc.bmj.com/content/13/3/e… @danafarber.bsky.social jitc.bmj.com/content/13/3...64

Timothy A. Yap, MBBS, PhD, has been appointed editor-in-chief of the AACR journal Clinical Cancer Research. Dr. Yap is co-director for the AACR/ASCO Methods in Clinical Cancer Research Workshop and a past cochair of the AACR Annual Meeting Clinical Trials Committee. www.aacr.org/about-the-aa...

Certainly a worthy topic of discussion in #ProstateCancer #Trials and beyond. Complex discussion with many considerations, but one whose time has come and should include disease experts, industry and regulatory. @oncologynews.bsky.social bit.ly/4kaza5K

PCF Science is now on BlueSky! Follow us for prostate cancer research news & building the prostate cancer research community.

Thank you for the invite and the innovative format. Was great to chat with such an enthusiastic and engaged group. Super hospitality. Thank you for the awesome discussion 😊

The true value of PFS endpoints in prostate cancer - Ravi Madan @ravimadan.bsky.social oncodaily.com/science/ravi... #Cancer #Medicine #Health #ProstateCancer #CancerResearch #Oncology #OncoDaily

Good to see #wolverine & trend to OS in #MDT in #ProstateCancer @ascocancer.bsky.social #GU25 Many key❓remain ✴️ who gets benefit (we can tx all but do we need to?) ✴️ ADT or not? ✴️ ARPI or not? ✴️ need to distinguish between oligomet vs #PSMA+ #BCR - 2 very different populations & biologies

Watching #BCR session @asco #GU25 it is very clear there is a drive to treat #BCR asap esp w/+ #PSMA But there is no data supporting a curative strategy & in that context deferring therapy max’ing #QOL is quite reasonable given JHU MFS data below ascopubs.org/doi/10.1200/...

Appreciate Dr. Alicia Morgans acknowledging the fundamental disconnect we often observe between toxicity we observe in clinic and pt reported outcomes in #ProstateCancer Also glad to hear her discuss options moving forward. #GU25 @ascocancer.bsky.social

#GU25 today had an emulated trial & concerns re: lack of cross-over Although future efforts should be made to max X-over it could be interesting to emulate a X-over based on subset that did…maybe🤔 Would require someone smarter than me & probably pt level data #ProstateCancer

Intriguing CT DNA presented by Dr. Johann DeBono suggesting the value in assessing treatment response #PSMAfore #Lu-psma #mCRPC #ProstateCancer Especially appreciate comparison to PSA50 responses given it’s already in clinic It does make me wonder - what if we looked at PSA80? #GU25

Dr. Louise Emmett presents OS data from #Enzalutamide +/- #Lu-psma in 1st line mCRPC #ProstateCancer Intriguing data to be sure but would have appreciated a built in cross-over given equivalent OS seen in #PSMAfore in 2nd line mCRPC when ARPI before or after Lu-psma #GU25 @ascocancer.bsky.social

Dr. Louise Emmett presents OS data from #Enzalutamide +/- #Lu-psma in 1st line mCRPC #ProstateCancer I especially appreciate Dr. Emmett showing a slide that includes on limitations in her data. It is required for papers. Probably should be for oral presentations @asco #GU25

Dr. Kevin Kelly reviews emerging therapeutic targets in #ProstateCancer @asco #GU25

Yes, and you highlight something that may be patient population specific whereby QoL measures in highly motivated volunteers in clinical trials may be less generalizable in practice

Dr. Surasi reviews ongoing extensive studies in #ProstateCancer with #Lu-PSMA @asco #GU25

Worth revisiting the #BRCAway trial from #GU24 in the context of #GU25 and #Talapro2 With regard to evaluation of sequencing #Parp and #ARPI the numbers of pts are very small (8 with cross over) and the CIs are very wide. #ProstateCancer

A related question on #Talapro2 that remains unanswered is sequencing of #ARPI & #parp aside from a very small phase 2 trial with far too few pts Sequencing #Parp would defer toxicity for mos-yrs & worth noting that low% of mCRPC pts getting 2nd line tx predates #parp era #GU25

These are the 2 key slides from the #Talapro2 presentation @asco #GU25 Where HR crosses 1.0 in pts w/no known HRR mutation status & Gd3 toxicity difference of 75% vs 45% I think there is still much to discussion to be had of value of #PARP +#ARPI in unselected #ProstateCancer