RELAZIONE TRA “STAGE MIGRATION” E

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RELAZIONE TRA “STAGE MIGRATION” E INVASIONE LINFONODALE NEL TUMORE PROSTATICO: RISULTATI DI UN SINGOLO ISTITUTO NEGLI ULTIMI 20 ANNI Fossati N, Abdollah F, Larcher A, Montorsi F, Briganti A, Guazzoni G Urological Research Institute, Vita-Salute San Raffaele University Department of Urology, San Raffaele Scientific Institute Milan, Italy

Introduction Previous studies have shown a decrease in the prevalence of prostate cancer (PCa) lymph node metastases in the recent years. However, these data might be biased by decreased rates and extents of pelvic lymph node dissections (PLND). We therefore assessed the evolution of rates and tumor characteristics of men with node positive disease at radical prostatectomy (RP) and extended PLND (ePLND) at a single tertiary referral center over the last two decades. Abdollah F, Eur Urol 2010; 58:882-892 Galper SL, J Urol 2006; 175:907-912

Materials and Methods 5274 PCa patients treated with open RP and ePLND (1990 - 2010). All patients received an anatomically defined ePLND.

Materials and Methods Year-per-year trends of lymph node invasion (LNI) rates and clinical and pathological characteristics were examined. The same analyses were repeated according to cancer characteristics, after stratification of patients into: - Low risk: PSA<10 ng/ml, clinical stage T1 and BxGS ≤ 6 - High risk: PSA>20 ng/ml or clinical stage T3 or BxGS 8-10 - Intermediate risk: all the remaining patients Univariable and multivariable logistic regression analyses addressed predictors of LNI, including year of surgery as predictor as well as patient and tumor characteristics.

classified according to year of surgery. Results Descriptive characteristics of 5274 patients treated with RP and ePLND, classified according to year of surgery. Overall 5274 (100%) 1990-1995 420 (8.0%) 1996-2000 984 (18.7%) 2001-2005 2001 (37.9%) 2006-2010 1869 (35.4%) p value NCCN classification Low-risk Intermediate-risk High-risk 1473 (27.9) 2298 (43.6) 1503 (28.5) 54 (12.9) 171 (40.7) 195 (46.4) 240 (24.4) 324 (32.9) 420 (42.7) 604 (30.2) 944 (47.2) 453 (22.6) 575 (30.8) 859 (46.0) 435 (23.3) <0.001 Pathological stage T2 T3a T3b T4 3469 (65.8) 809 (15.3) 888 (16.8) 108 (2.0) 227 (54.0) 63 (15.0) 109 (26.0) 21 (5.0) 617 (62.7) 135 (13.7) 188 (19.1) 44 (4.5) 1395 (69.7) 280 (14.0) 308 (15.4) 18 (0.9) 1230 (65.8) 331 (17.7) 283 (15.1) 25 (1.3) Pathological GS ≤6 3+4 4+3 ≥8 2247 (42.6) 1556 (29.5) 681 (12.9) 790 (15.0) 261 (62.1) 65 (15.5) 25 (6.0) 69 (16.4) 592 (60.2) 180 (18.3) 95 (9.7) 117 (11.9) 788 (39.4) 664 (33.2) 275 (13.7) 274 (13.7) 606 (32.4) 647 (34.6) 286 (15.3) 330 (17.7) N° of LN removed Mean Median Range 17.4 16.0 5.0-64.0 17.5 5.0-48.0 15.2 14.0 7.0-40.0 16.7 15.0 7.0-62.0 19.4 18.0 Lymph node invasion pN0 pN1 4544 (86.2) 730 (13.8) 334 (79.5) 86 (20.5) 838 (85.2) 146 (14.8) 1755 (87.7) 246 (12.3) 1617 (86.5) 252 (13.5)

classified according to year of surgery. Results Descriptive characteristics of 5274 patients treated with RP and ePLND, classified according to year of surgery. Overall 5274 (100%) 1990-1995 420 (8.0%) 1996-2000 984 (18.7%) 2001-2005 2001 (37.9%) 2006-2010 1869 (35.4%) p value NCCN classification Low-risk Intermediate-risk High-risk 1473 (27.9) 2298 (43.6) 1503 (28.5) 54 (12.9) 171 (40.7) 195 (46.4) 240 (24.4) 324 (32.9) 420 (42.7) 604 (30.2) 944 (47.2) 453 (22.6) 575 (30.8) 859 (46.0) 435 (23.3) <0.001 Pathological stage T2 T3a T3b T4 3469 (65.8) 809 (15.3) 888 (16.8) 108 (2.0) 227 (54.0) 63 (15.0) 109 (26.0) 21 (5.0) 617 (62.7) 135 (13.7) 188 (19.1) 44 (4.5) 1395 (69.7) 280 (14.0) 308 (15.4) 18 (0.9) 1230 (65.8) 331 (17.7) 283 (15.1) 25 (1.3) Pathological GS ≤6 3+4 4+3 ≥8 2247 (42.6) 1556 (29.5) 681 (12.9) 790 (15.0) 261 (62.1) 65 (15.5) 25 (6.0) 69 (16.4) 592 (60.2) 180 (18.3) 95 (9.7) 117 (11.9) 788 (39.4) 664 (33.2) 275 (13.7) 274 (13.7) 606 (32.4) 647 (34.6) 286 (15.3) 330 (17.7) N° of LN removed Mean Median Range 17.4 16.0 5.0-64.0 17.5 5.0-48.0 15.2 14.0 7.0-40.0 16.7 15.0 7.0-62.0 19.4 18.0 Lymph node invasion pN0 pN1 4544 (86.2) 730 (13.8) 334 (79.5) 86 (20.5) 838 (85.2) 146 (14.8) 1755 (87.7) 246 (12.3) 1617 (86.5) 252 (13.5)

Results Year-per-year trend analysis of lymph node invasion rates in the overall patient population. Year-per-year trend analysis of lymph node invasion rates, according to NCCN risk groups.

Results Univariable and multivariable logistic regression analyses predicting lymph node invasion (LNI) in 5274 patients treated with RP and ePLND. Univariable analysis Multivariable analysis OR (95% CI) p value Year of surgery category 1990-1995 1996-2000 2001-2005 2006-2010 1.00 (Ref.) 0.68 (0.5-0.91) 0.54 (0.41-0.71) 0.61 (0.46-0.79) --- <.001 0.009 0.83 (0.57-1.21) 0.76 (0.53-1.09) 0.68 (0.47-1.02) 0.3 0.1 0.06 PSA level (ng/ml) 1.04 (1.03-1.04) 1.02 (1.01-1.02) Pathological stage T2 T3a T3b T4 8.58 (6.31-11.67) 56.42 (42.97-74.08) 80.52 (51.04-127.03) 5.32 (3.85-7.36) 25.93 (19.25-34.92) 25.13 (14.95-42.25) Pathological Gleason score ≤6 3+4 4+3 ≥8 2.55 (1.92-3.38) 6.71 (5.03-8.96) 23.62 (18.19-30.66) 1.62 (1.16-2.25) 2.6 (1.83-3.71) 4.69 (3.37-6.52) 0.005 N° of LN removed 1.05 (1.04-1.06) 1.04 (1.03-1.06)

Results Univariable and multivariable logistic regression analyses predicting lymph node invasion (LNI) in 5274 patients treated with RP and ePLND. Univariable analysis Multivariable analysis OR (95% CI) p value Year of surgery category 1990-1995 1996-2000 2001-2005 2006-2010 1.00 (Ref.) 0.68 (0.5-0.91) 0.54 (0.41-0.71) 0.61 (0.46-0.79) --- <.001 0.009 0.83 (0.57-1.21) 0.76 (0.53-1.09) 0.68 (0.47-1.02) 0.3 0.1 0.06 PSA level (ng/ml) 1.04 (1.03-1.04) 1.02 (1.01-1.02) Pathological stage T2 T3a T3b T4 8.58 (6.31-11.67) 56.42 (42.97-74.08) 80.52 (51.04-127.03) 5.32 (3.85-7.36) 25.93 (19.25-34.92) 25.13 (14.95-42.25) Pathological Gleason score ≤6 3+4 4+3 ≥8 2.55 (1.92-3.38) 6.71 (5.03-8.96) 23.62 (18.19-30.66) 1.62 (1.16-2.25) 2.6 (1.83-3.71) 4.69 (3.37-6.52) 0.005 N° of LN removed 1.05 (1.04-1.06) 1.04 (1.03-1.06)

Conclusions A significant reduction in LNI rates over time was observed in our large cohort of patients homogeneoulsy treated with anatomically defined ePLND over two decades. However, contemporary intermediate and high risk patients still harbor a significant LNI risk if treated with ePLND. In consequence, stage migration does not justify omitting or limiting the extent of PLND in intermediate and high risk PCa patients.

RELAZIONE TRA “STAGE MIGRATION” E INVASIONE LINFONODALE NEL TUMORE PROSTATICO: RISULTATI DI UN SINGOLO ISTITUTO NEGLI ULTIMI 20 ANNI Fossati N, Abdollah F, Larcher A, Montorsi F, Briganti A, Guazzoni G Urological Research Institute, Vita-Salute San Raffaele University Department of Urology, San Raffaele Scientific Institute Milan, Italy