Management of Lymph Node Metastasis after Radical Prostatectomy

1. Management of Lymph Node Metastasis after Radical Prostatectomy Karim Touijer , MD, MPH. Attending Surgeon Memorial Sloan-Kettering Cancer Center No disclosures

2. intermediate risk Open Lap Low Risk Robotic High risk Low Risk

3. Trends in initial treatment of low-risk prostate cancer Memorial Sloan-Kettering Silberstein Jl et al. Reverse stage shift at a tertiary care center: escalating risk in men undergoing radical prostatectomy. Cancer 2011;117:4855-60. United Kingdom McVey GP et al. Temporal trends in initial treatment of low-risk prostate cancer. BJU Int 2010;106:1161-64.

5. Pathological outcomes by NCCN risk

6. Misconceptions • Nodal disease equates systemic disease • No role for local therapy

8. General Applicability Concerns • Large metastatic burden at presentation • Therapy withheld until bone metastasis developed

12. 1 node + 2 nodes + >2 nodes +

13. No consensus in the management of node positive disease • Choice of Tx is driven by physician’s preference or institutional standards • Observation and treatment after biochemical recurrence • Adjuvant androgen deprivation therapy (ADT) • Adjuvant ADT + External Beam Radiation Therapy (EBRT) • Benefit of immediate adjuvant treatment over observation is unknown

15. Survival Analysis of Patients with Node Positive Prostate Cancer after Radical Prostatectomy Comparing Observation vs. Adjuvant Androgen Deprivation Therapy Alone vs. Adjuvant Androgen Deprivation Plus External Beam Radiation Therapy. Karim A. Touijer; R. JefferyKarnes; Niccolo Passoni, Daniel D. Sjoberg,; Melissa Assel, Nicola Fossati, Giorgio Gandaglia,James A. Eastham; Peter T. Scardino;Andrew Vickers, Cesare Cozzarini, Francesco Montorsi, Alberto Briganti.

16. Study Design • Retrospective analysis • N+ after radical prostatectomy • MSKCC, Mayo and San Raffaele, Milan • 1988 – 2010 • Choice of Tx primarily driven by practice patterns or standard of care at each institution

17. Patients and Methods • 1471 patients • Adjuvant therapy: within 6 months of surgery • 50 patients were missing information on type of therapy • 33 were treated more than 6 months • 1388 men eligible for analysis

18. Objective To compare difference in overall survival between three different management strategies in men with node positive prostate cancer after radical prostatectomy

19. Results

20. Kaplan-Meier curve foroverall survival stratified by treatment group. Black line is ADT+EBRT, blue line is ADT, and red line is observation.

24. Multivariable competing risk regression with death from other causes as the outcome and cancer death as the competing event

25. Quantifying the Survival Benefit

27. Combined androgen deprivation and radiation versus either modality alone or observation after radical prostatectomy in patients with pathologic node-positive prostate cancer: analysis of a national hospital cancer registry database Zareba P, James Eastham, Peter Scardino, Karim A Touijer • The National Cancer Data Base (NCDB) • 5,909 patients treated with RP • 2004 and 2011. • Median follow-up was 4.5 years for survivors. J Urol 2017 epub

28. 61% were managed with observation, • 23% with ADT alone, • 5% with RT alone • 11% with ADT and RT

33. Cumulative incidence of death due to any cause stratified by number of adverse pathologic risk factors (Gleason score ≥8, stage ≥T3b and positive margins) • Low risk: 0-1 risk factors • Intermediate risk :2 risk factors • High risk: 3 risk factors

34. Lessons Learned • Node positive is a hetergeneous group • Maximizing local control with radiation therapy in combination with ADT improves survival • Multimodality therapy with radiation and ADT after surgery is of greatest value in patients with the worst pathologic features

35. What is the next step? • Molecular imaging could refocus the debate • Better staging • imaging guided therapies