Tony Felefly

I could not have done it better! @TylerSbrt7 gets all the key messages across for the ProtecT surgical review 👇🏻 Next stop: looking at 20-year outcomes in more specimens AND doubling down on efforts to improve early detection of high-grade, T3b cribriform disease 🔬🩻

Thanks Tyler! My take home message is that if cribriform present AS not recommended, and cribriform negative GG1 and low volume GG2 and no concern for T3b, that RP and RT and AS similarly effective. However for those with cribriform and/or multiple adverse features the DM rate was high with RP. Similar to what we showed in high risk PCa @Soum_Roy_RadOnc. Likely driven by multimodality treatment of synergy with RT+ADT and low utilization of multimodal treatment with RP. That is getting worse with now people not giving early SRT and waiting for imaging to be positive and find mets.

🚨The sequel is here!! The other 👞 drops. Cribriform morphology in ProtecT — now in prostatectomy specimens #ProstateCancer #radonc #UroSoMe @UroToday @APCCC_Lugano @PCF_Science @OncoAlert 🧵1️⃣

@TylerSbrt7 @SbrtSean @PCaParker @jmmrad @aleberlin2 @ZilliThomas @Soum_Roy_RadOnc @a_dalpra @KOSJ12 @Xristodouleas @drjefstathiou @NicholasZaorsky @DrHowardSandler @BrandonMahal @prostatemd @DrStish @tjroycemd @UCSD_Urology @UCSDRadMed @ASTRO_org @ESTRO_RT @somera_mx @AmericanCancer @Uroweb @OncoAlert @PCF_Science @APCCC_Lugano @urotoday @AOmlin @Silke_Gillessen @AmerUrological @PChoyke @declangmurphy @geoffsonn @andreasroder1 @LambAlastair @LabBryant @KeithKow @daviesbj @RenuEapen @mleapman @Daniel_Urologia @DrAdamMurphy @veerukasi @ProfHadaschik @mrsprostate @JuddMoul @DanLinMD @yawnyame 🤯

@SbrtSean @PCaParker @jmmrad @aleberlin2 @ZilliThomas @Soum_Roy_RadOnc @a_dalpra @KOSJ12 @Xristodouleas @drjefstathiou @NicholasZaorsky @DrHowardSandler @BrandonMahal @prostatemd @TonyFelefly @DrStish @tjroycemd @UCSD_Urology @UCSDRadMed @ASTRO_org @ESTRO_RT @somera_mx @AmericanCancer @Uroweb @OncoAlert @PCF_Science @APCCC_Lugano @urotoday @AOmlin @Silke_Gillessen @AmerUrological @PChoyke @declangmurphy @geoffsonn @andreasroder1 @LambAlastair @LabBryant @KeithKow @daviesbj @RenuEapen @mleapman @Daniel_Urologia @DrAdamMurphy @veerukasi @ProfHadaschik @mrsprostate @JuddMoul @DanLinMD @yawnyame It still thinks I am a bot. The system is not working!

🤖hacker stole my @TylerSbrt account. @X 🤖 says it can’t tell that I am me. Sad to lose my 📸 w/ friends and 🏃🏼 X won’t fix it—says they can’t tell I am me. Tagging people 👇🏼 whose handles I have on hand to try to get my Twitter community back 🙏🏼

@HenningWillers @Support @X @TylerSbrt7 @AshleyGWinter And yet they're speaking about X-money, while not able to protect accounts' identities!🤯

And another account hacked by bots 😡 @Support - what is going on with @X ❓ Time to leave❓❓ @TylerSbrt7 @AshleyGWinter

@TylerSbrt7 @cpeedell @SeibertLab @IJROBP @RO_GreenJournal @ARRO_org @ASTRO_org @ESTRO_org @CZamboglou @alison_tree @DrSpratticus @subatomicdoc @PBlanchardMD @DrAndrewLoblaw @SbrtSean @NehaVapiwala @piet_ost @seanmmcbride I just saw that your account was hacked! Unbelievable! 🤯 Maybe it's me, but it also seems that notifications are not being sent to people when you mention them! @X should do a better job than this!!

@TonyFelefly @cpeedell @SeibertLab @IJROBP @RO_GreenJournal @ARRO_org @ASTRO_org @ESTRO_org @CZamboglou @alison_tree @DrSpratticus @subatomicdoc @PBlanchardMD @DrAndrewLoblaw @SbrtSean @NehaVapiwala @piet_ost @seanmmcbride Thank you, Tony! Yes, many papers suggest tumor underestimated on imaging. But that would be true in FLAME, too, so maybe penumbra rescues us. Also, I worry about the lesion measurements—not very reliable link.springer.com/10.1007/s00330…

Let’s talk about prostate and urethra contouring on MRI. Three recent 📄📄📄 @SeibertLab #radonc #ProstateCancer 🧵1️⃣ @IJROBP @RO_GreenJournal @ARRO_org @ASTRO_org @ESTRO_org

Amazing work (as always!). Would be great to have such data on PET and MRI correlation with whole-mount pathology. I recently came across this study from Cedars-Sinai, no imaging-path fusion and not whole-mount slides, but it suggests PET and MRI under-estimate the DIL size. Looking forward to your team's paper(s)!! sciencedirect.com/science/articl…

@cpeedell @SeibertLab @IJROBP @RO_GreenJournal @ARRO_org @ASTRO_org @ESTRO_org @CZamboglou @alison_tree @DrSpratticus @subatomicdoc @PBlanchardMD @DrAndrewLoblaw @SbrtSean @NehaVapiwala @piet_ost @seanmmcbride Yes, pragmatism and empirical data are key. As ever, we cannot let perfection be the enemy of good Meanwhile, my group is working on quantitative MRI (and PSMA PET) against whole-mount histopathology from RP specimens. 1st paper under review

@druizuroonco @DrSpratticus Not sure I follow. For sure we can't extrapolate the number of metastases from conventional imaging to PSMA-PET in order to define a Low-volume subset, but this doesn't invalidate the fact that lower disease burden translates into a better benefit for mHSPC

@TonyFelefly @DrSpratticus But that study says exactly the same thing: how to extrapolate data from Stampede to the era of PSMA PET?

#EAU26 Curious to study team or others how the trial was allowed to run when EAU guidelines recommends RT in low volume mHSPC? How are you justifying withholding a treatment that improves rPFS and debatably OS? Control arm should be SOC systemic tx plus RT to primary, like in STAMPEDE. @Prof_Nick_James @alison_tree @achoud72 @parker @nickva1 @Uroweb @piet_ost @_ShankarSiva

@druizuroonco @DrSpratticus The benefit from RT is expected to be even higher with lower disease burden jamanetwork.com/journals/jamao…

@DrSpratticus PET PSMA was not available at the Stampede study.

#EAU26 Kudos to Lutectomy authors. Was bound to happen eventually and who better to do it. Neoadj trials w/ RP are generally academic and uncommonly patient centric. Bold statement, but why? 1. Neoadj definitionally over treats men. Adj RT has large BCR benefits. Not used bc PCa has PSA and some men are cured from RP. Better to test w/ savage RT as done with nearly all agents. 2. If recurrence post RP that 100% will recur that point #1 irrelevant, RP generally not optimal local therapy as most will get postop RT+ADT. 3. Post op RT still used at very high rates in all neoadj trials so often neoadj means triplet if not quadruplet therapy = cost and toxicity. 4. Actions speak louder than words and I don’t think patients or urologists support routine neoadj or adj tx for localized PCa. Adj RT rates were 5% when guideline endorsed, and neoadj chemoADT had OS benefit (HR <0.7) in CALGB trial and no one wants to use it and deemed it too toxic. ePLND also poor utilization. Pharma loves funding/running these trials as they get tissue, but that goes back to my first point…it is academic. They also like these trials as all men get the treatment and if positive great for their drug utilization. Controversial as academics love running these trials. Curious to others thoughts. @urotoday @Uroweb @APCCC_Lugano @ASCO @UroOnc @SeibertLab @piet_ost @ASTRO_Chair @WallisCJD @montypal @AmarUKishan @jamesbyu @DrMLChua @Adam_Weiner535 @HimanshuNagarMD @Dr_RaviMadan

Interesting perspective. I personally would posit that there is currently no one backbone for mHSPC and highly patient specific. LV sync: ADT+RT is backbone and ARPI personalized by biomarkers and age. Imagine 177Lu-PSMA may go in place of ARPI eventually, reinforcing that point. LV meta: many do MDT alone +\- ADT. ARPI has no proven benefit in oligomet space by PSMA PET. Personalization key. We showed no OS benefit for ARPI in synchronous LV in men >70yo, especially in context of RT to primary.

In PEACE-1 they used 74Gy/37fr. We typically use 60Gy/20fr, I don't see why we shouldn't use full dose. I think STAMPEDE schedules were conceived to reduce side effects (while benefit was still under investigation), but honestly with modern RT, I don't think there would be much difference. I do believe the trend is favoring SBRT now, perhaps a GU-005 prescription scheme to keep side effects a-minima

@PCaParker @TonyFelefly @ChapinMD @piet_ost Is anyone using a different schedule? I find it hard to recommend 6 weeks of treatment when most SBRT cases are done in 1,5 week.

Congrats @ChapinMD for this trial. A power issue or really no effect from prostatectomy in de novo mHSPC?

@ChapinMD @jryckman3 @scserendipity1 @piet_ost @EUplatinum Congratulations!! Looking forward to it!!

@jryckman3 @scserendipity1 @TonyFelefly @piet_ost Thanks @jryckman3. Full publication available in @EUplatinum today.

Good riddance! But if I understood correctly, they kept it for staging, just not for screening. And I don't understand the association between being symptomatic and DRE recommendation, as most symptoms are BPH-related, and most advanced tumors are actually asymptomatic. Did they elaborate on this point?

#EAU26 DRE not recommended for asymptomatic men. What are people’s thoughts on need for routine DRE in era of MRI? @ChapinMD @urotoday @UroOnc @Uroweb @wandering_gu @BogdanaSchmidt @CanesDavid @DrMLChua @HimanshuNagarMD @AmarUKishan @piet_ost @alison_tree @declangmurphy

@Soum_Roy_RadOnc @ChapinMD @piet_ost Too humble Soum!! Always great to have your thoughtful insights, and of course your biostat expertise!!

@TonyFelefly @ChapinMD @piet_ost Also tremendously honored to be tagged with some of the luminaries...I rather sit back, relax, and learn from them....

#EAU26 Multiple learnings from the Brazilian RCT of RP w/ limited vs extended PLND. Negative overall, but subset analysis for GG3-5 positive. 1. In patients w/ GG3-5 disease --> bRFS benefit of ePLND @VickersBiostats 2. Progression is extremely common w/ ~75% of patients s/p RP developing BCR by 4.5 years w/ limited PLND. Even with ePLND it was ~50% at 4.5 years. 3. If effect size so large this can be shown in just 69 patients, this should be a very easy Ph3 multi-center trial to run. All trials to date have been single center and did not meet primary endpoint in overall population. Lets get some definitive data already as this is a big difference for patients. @ChapinMD @wandering_gu @EdwardSchaeffer @ASCO @declangmurphy @urotoday

Fair point about ARPI! I don't fully agree. To be clear, I am talking here about low-volume mHSPC. Few points: 1- I wouldn't say PEACE-1 showed no OS benefit. It doesn't prove a benefit, neither does it disprove one. HR for SOC+Abi +/-RT was 0.77 (Curves below). There is certainly a trend. I think we need a higher N for the ARPI subgroup. There was however a signicant improvement in CRFS. 2- In a NMA (@soum_roy_radonc) with Bayesian pairwise comparison, the best treatment was SOC+ARPI+RT, and was associated with reduced mortality wrt SOC+ARPI europeanurology.com/article/S0302-… 3- STOPCAP meta-analysis (including PEACE-1 data) showed an OS HR of 0.92 (0.84-1.0) for RT for all-comers, low and high-volume (Forest plot below). For low-volume, OS HR was 0.79 (0.67-0.93). annalsofoncology.org/article/S0923-… urotoday.com/conference-hig… So based on the above, I think it's safe to say that RT to the primary is beneficial for low-volume mHSPC treated with ADT +/- ARPI. PEACE-1 cannot rule out an OS benefit for the ADT+ARPI subgroup, mainly due to small N and Frequentist design. It does however prove a CRFS benefit. On another hand, a Bayesian comparison (NMA above) showed that these patients most likely benefit from RT. In light of these, I think it's hard to NOT recommend RT even with ARPI. Wondering what is the current practice at your institution. Also curious to know what other Rad-Onc colleagues think about this @pcaparker @soum_roy_radonc @drspratticus @tylersbrt @seanmmcbride @sbrtsean @alison_tree @vedangmurthy @piet_ost @paulsargos @jryckman3 @5_utr @adib_elio @protonstorey @docpriyamvada @_shankarsiva @albertobossial @amarukishan

@TonyFelefly @piet_ost Stampede arm H low volume indeed had an 8% benefit at 3 yrs and 12% at 5 years. Peace-1 showed no OS benefit with ARPIs added. So perhaps the story isn’t fully played out yet.

@ChapinMD @piet_ost We do have evidence of benefit with RT

@piet_ost To be fair only had low volume and 2/3 surgery 1/3 RT. So no effect demonstrated but with crossover to LT in 6. I’d be cautious to isolate surgery and would rather state the question of benefit is still uncertain for LT in M1 PC.