1 Background Lymph node dissection: how much is enough? Eila C. Skinner, MD Professor of Clinical Urology USC Keck School of Medicine Radical cystectomy is the gold standard for the treatment of invasive bladder cancer In last 20 years the focus has been on: Timing of surgery Type of urinary diversion Adjuvant or neoadjuvant chemotherapy Laparoscopic techniques But does the technique of surgery matter? YES Lymph node dissection Nodal drainage of the bladder Most experts agree that node dissection is an important component of cystectomy BUT How extensive a node dissection is enough?
2 Extent of Node Dissection Limited = obturator only Standard = to bifurcation of common iliac Extended = to IMA Mapping study using radioactive nanocolloid injected into detrusor Roth E URO 2010:57:205 Node mapping study (n=290, N+ = 81) % of positive nodes % of patients + nodes by level Node mapping study in 43 N+ patients Leissner J URol 2004:171:139 Vazino et al J Urol 2004 171:1830
3 USC Mapping study (n=408, 93 N+) Preop clinical stage < T2 Highest level of positive nodes III II I 28 % 15% 57 % Highest level of positive nodes III II I 21 % 17 % 62 % Impact of positive nodes: USC series (n=1054) Patients with nodes at Level I only have almost a 50% 5-year recurrence-free survival 1.00 RFS by most proximal extent of LN involvement (n=65) Probability of Survival 0.80 0.60 0.40 0.20 p=0.032 Level II + III Level I Stein J Urol 2003:170:35 0.00 0 1 2 3 4 5 6 7 8 Years Since Surgery
4 Chemotherapy is an important adjunct for Level III nodes Effect of adjuvant chemo on RFS in pts with positive LNs above the aortic bifurcation (n=30) Limited vs extended LND Consecutive series (1990-93 vs 1993-97) (n=184) All patients Organ-confined 1.00 p<0.001 Probability of Survival 0.80 0.60 0.40 0.20 No chemo (n=10) Chemo (n=20) 0.00 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 Years Since Surgery Poulson, Horn, Steven J Urol 1998:160:2015 Limited vs extended LND Two institutions 1987-2000, recurrence-free survival Cleveland Clinic Limited dissection 9n=336) Bern Extended dissection (n=322) SWOG 8710 Trial 317 patients 1987-98 randomized to MVAC + cystectomy vs cystectomy alone 109 institutions (half community hospitals) 106 different surgeons Type of node dissection none 24 (9%) limited 98 (37%) standard 146 (54%) Dhar J Urol 2008;179:873 Herr J et al. Urol 171:1823, 2004
5 SWOG 8710 Survival by number of nodes removed Impact of # nodes examined on overall survival after cystectomy SEER data 1988-1996 (n=1900) N0 < 10 N0 > 10 Herr J Urol 171:1823, 2004 Konety J Urol 2003:169:946 Probability of undergoing LND by year of cystectomy SEER data 1988-2004 (n=8000) Collaborative Group Extent of lymph node dissection 100 90 80 Any LND > 10 nodes > 10 nodes >5 nodes 70 60 50 40 30 20 10 None Limited Standard Extended 0 MSKCC n=553 Vanderbilt n=279 U Mich n=210 Baylor n=49 Hellenthal J Urol 2009:181:2490 Herr J Urol 171:1823, 2004
6 Node counts Influenced by pathologists diligence, node packaging, and patient differences Poor surrogate for the extent of dissection Konety, Herr, others recommend a minimum of 10 nodes for adequate node dissection Number of nodes required to detect first positive node Dangle J Urol 1010:183:499 Node Packaging May 2002-present Nodal tissue sent to pathology in individual packets Pic of packets No change in the basic limits of dissection
7 Extended Node Dissection No difference in N+ rate with node packaging Extended dissection Number of nodes removed Era # pts Median # nodes N+ (range) 100% No packaging 100% With packaging 80% 80% 1971-2001 1359 31 (1-96) 23 % 60% 40% 60% 40% 2002-2006 447 68 (0-132) 25 % 20% 0% < 15 15-30 > 30 20% 0% < 15 15-30 > 30 Updated from Stein JP et al J Urol 177:876, 2007 1971-2001 2005-2006 Extended dissection with packaging # nodes removed USC 2005-2006 (n=223) Number of positive nodes vs total nodes (n=54, 2005-2006) 120 60 50 40 30 20 10 100 80 60 40 20 20% cutoff 0 0-15 16-30 31-45 45-60 61-75 76-90 91-105 106-120 > 120 0 0 30 60 90 120 XY (Scatter) 1 XY (Scatter) 2 XY (Scatter) 3 XY (Scatter) 4
8 Complications of extended node dissection Time: extra 30-60 minutes Poulson, Brosner studies: no increase in complications USC experience: 2% lymphocele (no tx) and 2% lymphedema long term Lymph Node Dissection Conclusions Extent of node dissection has an impact on outcome A minimal or no node dissection is associated with worse outcome for both N+ and N- patients Patients with small volume nodal disease may be cured with a more extensive dissection Positive margins are deadly, and are associated with more limited node dissection. Lymph Node Dissection Questions? Is there additional benefit to the extended node dissection over the standard dissection in terms of regional or distant recurrence? Does our current N-stage system work in the face of extended dissection and node packaging? Does the 20% cutoff for node density still work?