Presentation with lymphadenopathy Theo M. de Reijke MD PhD FEBU Department of Urology Academic Medical Center Amsterdam
Rationale for RRP in N+ disease Prevention local problems Better survival in limited N+ disease Part of multimodal approach NO prospective data!!
Rationale for RRP in N+ disease Proceed with RRP in N+ patients? Retrospective data suggest benefit N=139, better progression-free and survival Frohmuller et al Eur Urol 27:202-206, 1999 N=158, CSS predicted by number of N+ nodes. OS 10-14% Steuber et al BJUint 107:1755-1761, 2011
Therapeutic rationale for PLND Breast cancer Mathiesen et al Acta Oncol 29:721-725, 1990 Gastric cancer Siewert et al Ann Surg 228:449-461, 1998 Gynecologic cancer Friedber Geburtshilfe Frauenheilk 49:423-427, 1989 Colorectal cancer Caplin et al Cancer 82:666-672, 1998 Bladder cancer Mills et al J Urol 166:19-23, 2001 Leissner et al BJU int 85:817-823, 2000 Konety et al J Urol 169:946-950, 2003
Is there a therapeutic benefit of eplnd? Retrospective studies demonstrated a benefit of eplnd in terms of biochemical recurrence-free survival, as well as on disease progression and long-term disease-free survival Bader et al J Urol 169:849, 2003 Allaf et al J Urol 172:1840, 2004
Rationale for RRP in N+ disease Is there a survival benefit in performing eplnd in N+ combined with RRP? Which template Standard vs eplnd N=360, 10 vs 22.2% N+, benefit in BPFS in intermediate- and high-risk patients (73.1 vs 85.7% and 51.1 vs 71.4%) Ji et al J Surg Res 178:779-784, 2012
Engel et al Eur Urol 57:754-761, 2010
Natural clinical course of N+ Outcome 1 pos. LN n=39 2 pos. LN >2pos. LN n=20 n=29 No progression 38% 10% 14% PSA-Progression 18% 30% 24% sympt. progression 44% 60% 62% DOD 8% 25% 36% Bader et al J Urol 2003
Is there a therapeutic benefit of eplnd? >1 node positive greater risk of prostate cancer death (RR=6.232, 95% CI 1.074-36.170; p=0.04) 1 positive node (RR=4.012, 95% CI 0.670-24.029; p=0.13 Joslyn & Konety Urology 68:121-125, 2006
Briganti et al Eur Urol 55:261-270, 2009
Is there a therapeutic benefit of eplnd? SEER database 1988-1991: n=57,764 diagnosed with pca 13,020 underwent radical prostatectomy Missing data on lymph nodes n=3838 Median survival time was 127 months Joslyn & Konety Urology 68:121-125, 2006
Is there a therapeutic benefit of eplnd? Greater number of lymph nodes removed and examined increases likelihood of finding lymph node metastases Greater number of lymph nodes removed increases prostate cancer-specific survival, even in node negative patients Patients with more than 1 positive node had significant greater risk of prostate cancerrelated death Joslyn & Konety Urology 68:121-125, 2006
Gakis et al Eur Urol 66:191-199,2014
Messing et al N Engl J Med 341:1781-1788, 1999
Messing et al Lancet Oncol 7:472-479, 2006
Schröder et al Eur Urol 55:14-22. 2009
Conclusions Impact of LND on outcome remains an open question Some studies report a beneficial effect of LND on outcome Patients with low N postive burden can be cured by local treatment
Recurence following RRP Approximately 30% will develop biochemical recurrence Approximately 15% of patients will die from prostate cancer Identification of site of recurrence is important Local recurrence is usualy treated with salvage EBRT Distant recurrence is treated with ADT (early or delayed)
Rationale for surgical treatment of local recurrence. Second chance for cure? Other tumours (testis, renal, colon)
Local recurrence following RRP -?? Improved imaging modalities available Real local recurrence Pelvic recurrence in lymph node Extra pelvic recurrence Bone lesion
Imaging and recurrence PSA based Bone scan MRI PET/CT (PET/MRI)
Indications for Choline PET scan? Predictors of PET positivity: PSA levels >1 ng/ml PSA velocity >1 ng/ml/y PSAdt <2-3 mo to <6 mo Initial tumour stage >pt3b or pn1
Rigatti et al Eur Urol 60:935-943, 2011
Abdollah et al Eur Urol 2014 Epub ahead of print
Oncological outcome of splnd Patiënt selection is important Clinical progression PSA >4 ng/ml (HR 2.13) Location of recurrence (retroperitoneal: HR 2.92) Gleason score 8-10 (HR 3.5)
Conclusion Local recurrence: preferred treatment is salvage radiotherapy at low PSA level Pelvic lymph node recurrence: perhaps role for surgery (or radiotherapy) Extent of surgery/multimodality Tx?? Investigational new treatment approach, which should be done within framework of trial
Decaestecker et al BMC Cancer 14:671, 2014 Primary endpoint: androgen deprivation therapyfree survival 6 Belgian hospitals are recruiting patients