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Highlights AUA 2017 - Ca de Próstata

Highlights AUA 2017 - Ca de Próstata. Antonio Carlos Lima Pompeo Prof. Titular - Disciplina de Urologia – FM-ABC Coordenador Depto Uro-Oncologia - SBU. Take Home Messages: Prostate Cancer Kirsten Greene, MD, MS, FACS Associate Professor and Vice Chair Department of Urology, UCSF.

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Highlights AUA 2017 - Ca de Próstata

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  1. Highlights AUA 2017 - Ca de Próstata Antonio Carlos Lima Pompeo Prof. Titular - Disciplina de Urologia – FM-ABC Coordenador Depto Uro-Oncologia - SBU

  2. Take Home Messages: Prostate Cancer Kirsten Greene, MD, MS, FACS Associate Professor and Vice Chair Department of Urology, UCSF

  3. Trends for the AUA 2017 (>900 abstracts) • Gleason grade Grade group • Screening: USPSTF impact on metastasis • Detection: mpMRI, fluid and tissue biomarkers • Surgery: crowdsourcing, technique vs experience • Transrectalvs transperinealbiopsy • Genetic markers and precision medicine

  4. Grade Group Zumsteg 2013, 2016; Mathieu 2017

  5. Grade group PD10-11 ANALYSIS OF THE PREDICTIVE UTILITY OF PROGNOSTIC GRADE GROUPS (PGG) FOR PREDICTING PERIOPERATIVE ONCOLOGIC OUTCOMES OF RADICAL PROSTATECTOMY IN THE SHARED EQUAL ACCESS REGIONAL CANCER HOSPITAL (SEARCH) DATABASE Ariel Schulman, Lauren Howard, Kae Jack Tay, Rajan Gupta, Efrat Tsivian

  6. USPSTF impact on Screening PD03-12 PROSTATE CANCER INCIDENCE STRATIFIED BY RACE AND GLEASON SCORE: A SEER DATABASE ANALYSIS OF THE USPSTF GUIDELINE ERADaniel Au, Johar Syed, Sameer Siddiqui Increase in high grade disease

  7. Rising Incidence of Metastatic Prostate Cancer in California, 1988-2014 Marc Dall’Era, Ralph de Vere White, Danielle Rodriguez, Rosemary Cress University of California Davis Comprehensive Cancer Center, Sacramento, CA Metastatic Non-Hispanic Whites Incidence rate APC Decreased low risk, increased metastasis Metastatic APC age 65-74 Incidence rate

  8. Detection: MRI, urine, serum, tissue markers Markers: SUO meeting Stacy Loeb, MD Which, when and how valuable?

  9. Prior Negative Biopsy, Elevated PSA Is high-quality mpMRI available? No Yes MRI Marker PIRADS <3 PIRADS >3 Targeted biopsy Marker Fenstermaker M et al. AUA 2017

  10. MRI fusion biopsy take home (>200 abstracts) • MP33-20 Smarttarget biopsy trial. Donaldson et al. no difference in visual estimation vs fusion • MP03-01 Qiu et al. MRI guided prostate biopsies fail to outperform standard TRUS guided biopsy in detecting high risk prostate cancer: a Bayesian network meta-analysis of 24 randomized controlled trials: found better overall detection than TRUS but equal high risk disease. China • PIRADS≥3 significant associated with detection of cancer on biopsy. MP38-03 Miakhil et al UK. , MP38-14 Gavin et al. Australia

  11. Transperineal vs transrectal biopsy approach • Both with mpMRI fusion or cognitive • Lower infection rates with transperineal biopsy • Anesthesia vs office based, costs

  12. ERSPT vs PROTECT, PIVOT trial late breaking abstract • PD03-01 PROTECT Metastases and death after 15 years of follow up… Jan Verbeek, Chris Bangma, Frank-Jan Drost, Monique Roobol • PD55-04 ERSPT vs PROTECT Drost et al. Low and intermediate risk. No difference in overall survival comparing surgery/radiation vs active monitoring • PIVOT: no decrease in prostate cancer specific or all cause mortality at 20 years comparing surgery and observation

  13. PIVOT Prostate Cancer Mortality No statistical difference HR = 0.63 (0.39 to 1.02); P=0.06 AR = 4.0% (-0.2 to 8.3)

  14. Surgery • Technique not as important as experience • Crowdsourcing can identify expertise • Open=robotic: outcomes and quality of life but better than laparoscopic • Fluorescent lymph node identification • Retzius sparing approach

  15. COMPLICATION RATES IN CONTEMPORARY PATIENTS TREATED WITH ROBOT-ASSISTED RADICAL PROSTATECTOMY Paolo Dell'Oglio, Armando Stabile, Emanuele Zaffuto, Giorgio Gandaglia, Nicola Fossati, Marco Bandini DOI: 10.1016/j.juro.2017.02.3292 Surgical expertise!

  16. Measuring to improve: patient reported outcomes during the first year after prostatectomy in a statewide collaborative Gregory B. Auffenberg*, Ji Qi, Rodney L. Dunn, Tae Kim, James Peabody, Mani Menon, and David C. Miller for the Michigan Urological Surgery Improvement Collaborative

  17. Results – surgeon variation 3 month urinary outcomes Top performers

  18. Patient factors do not define top performers Declining patient risk

  19. PF18-06 5 years follow-up of a prospective randomised controlled trial comparing laparoscopic versus robot-assisted radical prostatectomy: oncological and functional outcomes. F. Porpiglia, C. Fiori, R. Bertolo, M. Manfredi, F. Mele, D. Garrou, G. Cattaneo, D. Amparore, E. Checcucci, S. De Luca, R. Passera, R. M. Scarpa FUNCTIONAL RESULTS Continence rate Potency rate 60 patients 30 patients 1 year 4 years 1 year 4 years The continence and potency rates over time were higher in the RARP group (OR 2.47, p<0.021 and OR 2.35, p<0.028, respectively). b)

  20. Prospective Multicenter Comparison of Open and Robotic Radical Prostatectomy:The PROST-QA and PROST-QA/RP2 ConsortiumsPeter Chang MD MPH, Andrew Wagner MD, Meredith Regan ScD, Dattatraya Patil MBBS MPH, Catrina Crociani MPH, Larry Hembroff PhD, Linda Stork, Kyle Davis, John Wei MD MS, David Wood MD, Chris Saigal MD MPH, Mark Litwin MD MPH, Jim Hu MD MPH, Eric Klein MD, Adam Kibel MD, Gerald Andriole MD, Matthew Cooperberg MD MPH, Peter Carroll MD MPH, Joseph Smith MD, Misop Han MD, Alan Partin MD PhD, Martin Sanda MD, and the PROST-QA and PROST-QA/RP2 Consortiums

  21. Surgical approach is NOT a significant predictor of longitudinal HRQOL change over time Urinary Incontinence Sexual Open NS vs. robotic NS Open non NS vs. robotic non NS Prospective multicenter comparison of open and robotic radical PR AUA 2017 Urinary Irritation/Obstruction Bowel

  22. Conclusions • NO significant difference in HRQOL change over time by surgical approach (ORP or RALP) • RALP was associated with • Decreased blood loss/blood transfusions • Shortened length of hospital stay • Favorable pain, activity, incisional scores • Fewer infections • Fewer unplanned catheterizations • Fewer DVTs

  23. Best abstract Technical Skill Assessment of Surgeons Performing Robot-Assisted Radical Prostatectomy: Relationship Between Crowdsourced Review and Patient Outcomes KR Ghani, et al. • Higher skilled (Q4) surgeons had significantly lower: • Urethral catheter replacement rates (OR=0.44, p=0.005) • Readmission rates (OR=0.54, p=0.02) Online crowdsourced reviewers agreed with experts on the rank order of surgeons with the lowest skill scores

  24. Best abstract Focal Therapy of Prostate Cancer: Defining Treatment Margins Using MRI:Whole-Mount Co-Registration Results • Median treatment margin required was 10.7 mm. • Average treatment volume required was 11.4 cc. • 30% of average prostate volume • Mean tumor volume on MRI was 0.59 cc and 1.59 cc on prostatectomy specimen (p<0.001). • All men would have been successfully treated with hemi-gland ablation. Tonye Jones, Priester, Natarajan, Khoshnoodi, Grundfest, Leonard Marks

  25. Late breaking abstract Racial Disparities and Genetic Variabilities in Prostate Cancer Isaac Y. Kim, MD, PhD, MBA No Association between Exome seq and Race Significant inter-institutional variations in racial disparity. Possibility of yet-to-be identified institutional bias. Current body of data does not support modifyingthe AS criteria based on race.

  26. Frequency of DNA Repair Gene Mutations in Primary and Metastatic Prostate CancerAllison Glass1, Primo Lara, Jr.1, Ryan Hartmaier2, Ralph de Vere White1, John Mcpherson1, and Marc Dall’Era1, University of California Davis Medicine, Inc., Cambridge, MA • BRCA2 (11.43%) • ATM (5.77%) • MSH6 (2.46%) • MSH2 (2.14%) • ATR (1.60%) • MLH1 (1.28%) • BRCA1 (1.18%)

  27. Best abstract Current management of prostate cancer in AQUA Matthew Cooperberg, Raymond Fang, J. Stuart Wolf, Jr, Heddy Hubbard, Sanyog Pendharkar, Sunil Gupte, Kimberly Ross, Mary Nolin, and others

  28. Localized prostate cancer guidelines Risk stratification using grade groups D’Amico 1998, Epstein 1994

  29. CARE OPTION SUMMARY Very low and low risk

  30. Intermediate risk

  31. RISK STRATIFICATION • Clinicians should stage high-risk localized prostate cancer patients with cross sectional imaging (CT or MRI) and bone scan • Clinicians should recommend radical prostatectomy or radiotherapy plus ADT as standard treatment options for patients with high-risk localized prostate cancer • Do not recommend AS, focal therapy, primary ADT

  32. GUIDELINE STATEMENTS Additional Recommendation • Clinicians may consider referral for genetic counseling for patients (and their families) with high-risk localized prostate cancer and a strong family history of specific cancers (e.g., breast, ovarian, pancreatic, other gastrointestinal tumors, lymphoma) (Expert opinion) • BRCA2

  33. CÂNCER METASTÁTICO DA PRÓSTATA – AUA 2017 “Tendências” • CaP com alto volume sensível à castração • associação com Qt (docetaxel) – CHAARTED ou abiraterona (LATITUDE) • Tratamento local (tu primário) no CaP metastático • prostatectomia/Rdt • Melhor sequência terapêutica no mCaPCR ? • Marcadores (ARV-7) de resposta terapêutica a abiraterona/enzalutamida • Isótopos radioativos ligados ao antígeno específico de membrana prostática (PSMA) – actinium225 abiraterona enzalutamida docetaxel Sipuleucel ... radioterapia • Fatores a considerar • PS – sintomas • localização • disponibilidade • custos • “preferência” médico/paciente • ainda sem consenso ADT +

  34. Overall survival by extent of metastaticdisease at start of ADT - CHAARTED High volume Low volume Hazard Ratio 0.60 (95% CI 0.45-0.81) P=0.0006 ADT + DOC Not reached ADT + DOCMedian 49.2 mths ADT alone Not reached ADT alone Median 32.2 mths Hazard Ratio 0.63 (95% CI 0.34-1.17) P=1398 17-month benefit in median OS (from 32.2 to 49.2 months) for high disease volume SAGB.CAB.14.08.0382c 20/12/2019 Sweeney C et al. J Clin Oncol 2014;32(June 20 suppl):abstract LBA2 ADT: androgen deprivation therapy; DOC: docétaxel 75mg/m² plus prednisone

  35. Overall survival Might Men Diagnosed with Metastatic Prostate Cancer Benefit from Definitive Treatment of the Primary Tumor? A SEER-Based Study(M1a-c) Culp SH et al – EurUrol 2014 8185 pts – 2004-2011 retrospective No Surgery / Rdt – n = 7811 pts Radical Prostatectomy – n= 245 pts Brachytherapy – n = 129 pts PCa – specific mortality Conclusions: “definitive treatment of the prostate in men diagnosed with mPCa suggests a survival benefit in this population-based study”

  36. Potential biomarker that may predict resistance to Enzalutamide and Abiraterone Detection of AR-V7 in CTCs from men with mCRPC is associated with resistance to enzalutamide and abiraterone Enzalutamide Abiraterone Antonarakis et al, abst# 5001, 2014 ASCO

  37. AUA 2017 CaP: Tratamentofuturo? Isótopo radioativo (actinium225) ligado ao antígeno específico prostático de membrana PSMA Caso 1 Caso 2 • RESULTADOS • respostas: completa do PSA e do tumor avaliado por PET • toxicidade hematológica insignificante, sem supressão medular, boca seca (xerostomia)

  38. Thank you Obrigado!

  39. Model of 4K Score  Selective MRI 4K Score %HG CaP 5-32% >32% <5% No Biopsy Biopsy MRI ≥3 <3 • 54% of population in US 4KScore validation study had 5-32% risk of high-grade prostate cancer, and would potentially benefit from MRI Marzouk et al. AUA 2017, PD 40-08

  40. MRI PCA3 ≥35 AUC 0.69 AUC 0.82 Avoids 51% biopsies Misses 33% high grade Avoids 62% biopsies Misses 20% high grade MRI PCA3 ≥35 >3 Avoids 76% biopsies Misses 48% high grade Avoids 36% biopsies Misses 5% high grade

  41. Breaking news, Best of, Guidelines • PIVOT trial • Best abstracts: prostate cancer genetics • Late breaking abstracts • Localized prostate cancer guidelines

  42. Best abstract:Precision medicine Novel in vitro organoid technology to facilitate a precision medicine approach in the management of men with biochemical recurrence of prostate cancer Andre Joshi et a. Patient derived samples were successfully cultured in vitro PSA ELISA of conditioned media was positive RT-qPCR confirmed expression of prostate specific genes X4 Bright field image of patient derived organoid growing from biopsy (2 weeks in culture) Scale bar: 500µm 500um

  43. Best abstract: Diverse genomic landscape of low risk prostate cancer Matthew R. Cooperberg et al Unsupervised cluster analysis of UCSF low-risk cases reveals 3 distinct expression patterns, very similar to those previously described in breast and other cancers

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