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1655 IMPACT OF TUMOR THROMBUS CONSISTENCY (SOLID VS FRIABLE) ON CANCER-SPECIFIC MORTALITY IN PATIENTS WITH RENAL CELL CARCINOMA AND VENOUS TUMOR THROMBUS
Vol. 183, No. 4, Supplement, Tuesday, June 1, 2010
THE JOURNAL OF UROLOGY姞
1654
1655
LONG TERM SURVIVAL RATES AFTER RESECTION FOR LOCALLY ADVANCED KIDNEY CANCER
IMPACT OF TUMOR THROMBUS CONSISTENCY (SOLID VS FRIABLE) ON CANCER-SPECIFIC MORTALITY IN PATIENTS WITH RENAL CELL CARCINOMA AND VENOUS TUMOR THROMBUS
Matthew Frank O’Brien*, Thomas Jang, Angel Cronin, Christian von Bodman, William Lowrance, Melanie Bernstein, Michael Karellas, Paul Russo, New York, NY INTRODUCTION AND OBJECTIVES: Management of advanced renal cell carcinoma (RCC) has changed due to targeted therapy. Recently adjuvant targeted therapy clinical trials in locally advanced non-metastatic RCC (nmRCC) have begun. We report longterm survival rates against which these trials should be measured. METHODS: We identified 622 patients with locally advanced nmRCC who underwent nephrectomy from 1989 to 2008. 5 and 10 year progression-free (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Differences in recurrence-free and survival probabilities by various tumor features were tested by log rank test. RESULTS: 161 patients progressed and 193 patients died, with 76 having died from RCC. Median follow-up for patients who did not progress was 3.8 years. Tumor stage, histology, grade and lymph node status were significantly associated with both progression and survival (all p⬍0.002). 5 year PFS and OS are given in the table with 95% confidence intervals (CI). 10 year PFS for all patients with clear cell RCC was 57% (95% CI 50%, 64%). When stratifying by grade, 10 year PFS was 70% (95% CI 61%, 78%) for those with low grade clear cell tumors, and 33% (95% CI 18%, 49%) for those with high grade clear cell tumors. Adrenalectomy was performed in 398 (64%) cases and IVC thrombectomy in 58 (9%) cases. For lymph node positive patients, median PFS was 13 months and median OS was 71 months. CONCLUSIONS: Many patients with locally advanced nmRCC have favorable survival and may not require adjuvant therapy. Those with lymph node involvement or high grade RCC do poorly with surgery alone and enrolling these patients rather than all patients in adjuvant trials is paramount. Frequency %
5-year PFS %
5-year OS %
T3a
395 (64)
82 (78, 86)
84 (79, 87)
T3b/c
207 (33)
60 (52, 68)
62 (53, 70)
20 (3)
18 (4, 38)
19 (5, 41)
Tumor stage
T4 Tumor histology Clear Cell Chromophobe
442 (71)
70 (65, 75)
73 (67, 77)
56 (9)
85 (69, 93)
82 (66, 91)
Papillary
52 (8)
Oncocytoma
36 (6)
Unclassified
36 (6)
85 (70, 92) 100 51 (30, 68)
78 (61, 88) 100 51 (22, 74)
Tumor grade* Low (1/2)
206 (47)
82 (76, 87)
82 (75, 87)
High (3/4)
197 (45)
54 (44, 63)
64 (55, 73)
Not done
282 (45)
86 (81, 90)
79 (72, 84)
Negative
301 (48)
68 (62, 74)
73 (66, 79)
Positive
39 (6)
24 (10, 41)
58 (39, 73)
e639
Roberto Bertini, Marco Roscigno*, Massimo Freschi, Umberto Capitanio, Angiolilli Diego, Elena Strada, Giovanni Petralia, Francesco Sozzi, Rayan Matloob, Alberto Briganti, Milan, Italy; Luigi Da Pozzo, Bergamo, Italy; Anna Cremonini, Milan, Italy; Pierre Karakiewicz, Montreal, Canada; Francesco Montorsi, Patrizio Rigatti, Milan, Italy INTRODUCTION AND OBJECTIVES: We analyzed the effect of the consistency of a venous tumor thrombus (VTT) on cancerspecific mortality (CSM) in patients affected by renal cell carcinoma (RCC). METHODS: We retrospectively analyzed 174 patients with RCC and renal vein or inferior vena cava VTT who underwent radical nephrectomy and thrombectomy at our institute (1989-2007). All pathologic specimens were reviewed by a single uropathologist (MF), who had no knowledge of patient outcomes. Apart from traditional pathologic features, the morphologic aspect of a venous thrombus was evaluated to distinguish solid versus friable character. In a solid thrombus, tumor growth was compact and cohesive, with a rounded linear profile and, sometimes, a partial endothelial lining simulating a pseudocapsule. In a friable thrombus, tumor cells were intermingled with abundant necrosis and fibrin, and had a scalloped irregular profile and discohesive aspect, sometimes with thin papillary features. The prognostic role of thrombus consistency (solid vs friable) on CSM was assessed by means of Cox regression models. RESULTS: The median follow-up was 24 months. The VTT was solid in 107 (61.5%) and friable in 67 (38.5%) patients. The presence of a friable VTT increased the risk of having synchronous nodal or distant metastases, higher tumor grade, higher pathologic stage, and simultaneous perinephric fat invasion (PFI) (all p ⬍ 0.05). The median CSMfree survival was 33 months. The median CSM-free survival in patients with a friable or a solid VTT was 8 and 55 months, respectively (p ⬍ 0.001). At multivariable analyses, the presence of a friable VTT was an independent predictor of CSM (p ⫽ 0.02). The presence of a friable thrombus was the second most informative predictor (area under the curve [AUC] ⫽ 62%) after the variable depicting the presence of a synchronous metastasis (AUC ⫽ 68%). Moreover, inclusion of the variable “friable thrombus” in a base model including ECOG PS, Fuhrman grade, and presence of nodal disease and metastatic disease significantly increased the accuracy in predicting CSM (⫹2.5%; p ⬍ 0.001). On the contrary, extension of the tumor thrombus did not affect patient survival. CONCLUSIONS: In patients with RCC and VTT, the presence of a friable thrombus is an independent predictor of CSM. We suggest to introduce information about thrombus consistency into standard pathologic reports. More research is needed to better clarify the prognostic role of thrombus consistency in patient outcomes.
Lymph node status
Source of Funding: None
* For patients with Clear Cell histology
Source of Funding: None
1656 IMPACT OF THE INVASION OF PERINEPHRIC OR RENAL SINUS FAT IN PATIENTS WITH RENAL CELL CARCINOMA AND VENOUS TUMOR THROMBUS Elena Strada, Marco Roscigno*, Massimo Freschi, Giovanni Petralia, Francesco Sozzi, Anna Cremonini, Renzo Colombo, Alberto Briganti, Andrea Gallina, Valerio Di Girolamo, Francesco Montorsi, Patrizio Rigatti, Roberto Bertini, Milan, Italy INTRODUCTION AND OBJECTIVES: To evaluate the impact of perinephric fat invasion (PFI) or renal sinus fat invasion (RSFI) on cancer specific mortality (CSM), in patients with renal cell carcinoma (RCC) with neoplastic thrombus.
THE JOURNAL OF UROLOGY姞
1654
1655
LONG TERM SURVIVAL RATES AFTER RESECTION FOR LOCALLY ADVANCED KIDNEY CANCER
IMPACT OF TUMOR THROMBUS CONSISTENCY (SOLID VS FRIABLE) ON CANCER-SPECIFIC MORTALITY IN PATIENTS WITH RENAL CELL CARCINOMA AND VENOUS TUMOR THROMBUS
Matthew Frank O’Brien*, Thomas Jang, Angel Cronin, Christian von Bodman, William Lowrance, Melanie Bernstein, Michael Karellas, Paul Russo, New York, NY INTRODUCTION AND OBJECTIVES: Management of advanced renal cell carcinoma (RCC) has changed due to targeted therapy. Recently adjuvant targeted therapy clinical trials in locally advanced non-metastatic RCC (nmRCC) have begun. We report longterm survival rates against which these trials should be measured. METHODS: We identified 622 patients with locally advanced nmRCC who underwent nephrectomy from 1989 to 2008. 5 and 10 year progression-free (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Differences in recurrence-free and survival probabilities by various tumor features were tested by log rank test. RESULTS: 161 patients progressed and 193 patients died, with 76 having died from RCC. Median follow-up for patients who did not progress was 3.8 years. Tumor stage, histology, grade and lymph node status were significantly associated with both progression and survival (all p⬍0.002). 5 year PFS and OS are given in the table with 95% confidence intervals (CI). 10 year PFS for all patients with clear cell RCC was 57% (95% CI 50%, 64%). When stratifying by grade, 10 year PFS was 70% (95% CI 61%, 78%) for those with low grade clear cell tumors, and 33% (95% CI 18%, 49%) for those with high grade clear cell tumors. Adrenalectomy was performed in 398 (64%) cases and IVC thrombectomy in 58 (9%) cases. For lymph node positive patients, median PFS was 13 months and median OS was 71 months. CONCLUSIONS: Many patients with locally advanced nmRCC have favorable survival and may not require adjuvant therapy. Those with lymph node involvement or high grade RCC do poorly with surgery alone and enrolling these patients rather than all patients in adjuvant trials is paramount. Frequency %
5-year PFS %
5-year OS %
T3a
395 (64)
82 (78, 86)
84 (79, 87)
T3b/c
207 (33)
60 (52, 68)
62 (53, 70)
20 (3)
18 (4, 38)
19 (5, 41)
Tumor stage
T4 Tumor histology Clear Cell Chromophobe
442 (71)
70 (65, 75)
73 (67, 77)
56 (9)
85 (69, 93)
82 (66, 91)
Papillary
52 (8)
Oncocytoma
36 (6)
Unclassified
36 (6)
85 (70, 92) 100 51 (30, 68)
78 (61, 88) 100 51 (22, 74)
Tumor grade* Low (1/2)
206 (47)
82 (76, 87)
82 (75, 87)
High (3/4)
197 (45)
54 (44, 63)
64 (55, 73)
Not done
282 (45)
86 (81, 90)
79 (72, 84)
Negative
301 (48)
68 (62, 74)
73 (66, 79)
Positive
39 (6)
24 (10, 41)
58 (39, 73)
e639
Roberto Bertini, Marco Roscigno*, Massimo Freschi, Umberto Capitanio, Angiolilli Diego, Elena Strada, Giovanni Petralia, Francesco Sozzi, Rayan Matloob, Alberto Briganti, Milan, Italy; Luigi Da Pozzo, Bergamo, Italy; Anna Cremonini, Milan, Italy; Pierre Karakiewicz, Montreal, Canada; Francesco Montorsi, Patrizio Rigatti, Milan, Italy INTRODUCTION AND OBJECTIVES: We analyzed the effect of the consistency of a venous tumor thrombus (VTT) on cancerspecific mortality (CSM) in patients affected by renal cell carcinoma (RCC). METHODS: We retrospectively analyzed 174 patients with RCC and renal vein or inferior vena cava VTT who underwent radical nephrectomy and thrombectomy at our institute (1989-2007). All pathologic specimens were reviewed by a single uropathologist (MF), who had no knowledge of patient outcomes. Apart from traditional pathologic features, the morphologic aspect of a venous thrombus was evaluated to distinguish solid versus friable character. In a solid thrombus, tumor growth was compact and cohesive, with a rounded linear profile and, sometimes, a partial endothelial lining simulating a pseudocapsule. In a friable thrombus, tumor cells were intermingled with abundant necrosis and fibrin, and had a scalloped irregular profile and discohesive aspect, sometimes with thin papillary features. The prognostic role of thrombus consistency (solid vs friable) on CSM was assessed by means of Cox regression models. RESULTS: The median follow-up was 24 months. The VTT was solid in 107 (61.5%) and friable in 67 (38.5%) patients. The presence of a friable VTT increased the risk of having synchronous nodal or distant metastases, higher tumor grade, higher pathologic stage, and simultaneous perinephric fat invasion (PFI) (all p ⬍ 0.05). The median CSMfree survival was 33 months. The median CSM-free survival in patients with a friable or a solid VTT was 8 and 55 months, respectively (p ⬍ 0.001). At multivariable analyses, the presence of a friable VTT was an independent predictor of CSM (p ⫽ 0.02). The presence of a friable thrombus was the second most informative predictor (area under the curve [AUC] ⫽ 62%) after the variable depicting the presence of a synchronous metastasis (AUC ⫽ 68%). Moreover, inclusion of the variable “friable thrombus” in a base model including ECOG PS, Fuhrman grade, and presence of nodal disease and metastatic disease significantly increased the accuracy in predicting CSM (⫹2.5%; p ⬍ 0.001). On the contrary, extension of the tumor thrombus did not affect patient survival. CONCLUSIONS: In patients with RCC and VTT, the presence of a friable thrombus is an independent predictor of CSM. We suggest to introduce information about thrombus consistency into standard pathologic reports. More research is needed to better clarify the prognostic role of thrombus consistency in patient outcomes.
Lymph node status
Source of Funding: None
* For patients with Clear Cell histology
Source of Funding: None
1656 IMPACT OF THE INVASION OF PERINEPHRIC OR RENAL SINUS FAT IN PATIENTS WITH RENAL CELL CARCINOMA AND VENOUS TUMOR THROMBUS Elena Strada, Marco Roscigno*, Massimo Freschi, Giovanni Petralia, Francesco Sozzi, Anna Cremonini, Renzo Colombo, Alberto Briganti, Andrea Gallina, Valerio Di Girolamo, Francesco Montorsi, Patrizio Rigatti, Roberto Bertini, Milan, Italy INTRODUCTION AND OBJECTIVES: To evaluate the impact of perinephric fat invasion (PFI) or renal sinus fat invasion (RSFI) on cancer specific mortality (CSM), in patients with renal cell carcinoma (RCC) with neoplastic thrombus.