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RADICAL NEPHRECTOMY AND METASTATECTOMY COMBINED WITH IMMUNOTHERAPY FOR METASTATIC RENAL CELL CARCINOMA
937
938
IS THERE STILL A ROLE FOR HAND-ASSISTED LAPAROSCOPIC NEPHRECTOMY (HAL)?
INTERFERON ALPHA-2B AS MEDICAL SELECTION FOR NEPHRECTOMY IN PATIENTS WITH SYNCHRONOUS METASTATIC RENAL CELL CARCINOMA: A CONSECUTIVE STUDY
Appanna T.1, Martindale A.1, Goad J.1, Temelcos C.1, Clarke A.1, Asopa R.1, Cleeve L.2, Niall O.1
Bex A.1, Kerst M.2, Mallo H.2, Meinhardt W.1, Horenblas S.1, De Gast G.2
1
1
INTRODUCTION & OBJECTIVES: We have been performing laparoscopic nephrectomies since 2002 and have used the hand assisted technique on a regular basis. In light of the increasing demand for minimally invasive techniques in urology, we aim to report our results and to comment on the use of the hand port and its implications for the patient and on training.
INTRODUCTION & OBJECTIVES: Up to 25% of the patients with synchronous metastatic renal cell carcinoma (mRCC) treated with nephrectomy and interferon alpha-2b (IFN-α) will progress rapidly at metastatic sites and undergo needless surgery for an asymptomatic primary. We reversed the timing of surgery and immunotherapy and evaluated the role of initial IFN-α as selection for nephrectomy.
St. Vincent’s Hospital, Department of Urology, University of Melbourne, Melbourne, Australia, 2Melbourne Urology Group, Department of Urology, Melbourne, Australia
MATERIAL & METHODS: A combination of retrospective and prospective data collection was used to obtain patient demographics, operative details, pathology information and outcome data for all patients who underwent laparoscopic nephrectomy between April 2002 and June 2005 at St. Vincent’s Hospital and the Melbourne Urology Group in Melbourne, Australia. RESULTS: We performed 78 laparoscopic nephrectomies (47 of which were hand assisted) in the specified time period on patients with a mean age of 63.4 years. 38% of the public patients were operated on by a trainee/fellow as the primary surgeon and the median operating time was 180 mins. No differences were observed between pure and hand assisted laparoscopy (HAL) in terms of operative mortality and morbidity, in patient stay and analgesic use. CONCLUSIONS: Our results are in keeping with those of other published series. We have found the hand port to be a safe and effective tool for nephrectomy without the inherent risks of pure laparoscopy. As an incision is required to remove the kidney from the abdomen it seems illogical not to utilise that incision from the beginning of the case. The benefits are safer port placement, tactile feedback and early control of heavy bleeding. In addition trainees can rapidly get to grips with the technique. We would therefore advocate its use in all extirpative renal surgery and challenge the view that it is an inferior technique to pure laparoscopy.
The Netherlands Cancer Institute, Urology, Amsterdam, The Netherlands, 2The Netherlands Cancer Institute, Oncology, Amsterdam, The Netherlands
MATERIAL & METHODS: Sixteen patients with mRCC and the primary insitu received initial IFN-α for 8 weeks (2 weeks 5 x 3 x 106 IU/wk; 2 weeks 5 x 6 x 106 IU/wk; 2 weeks 5 x 9 x 106 IU/wk and 2 weeks 3 x 9 x 106 IU/wk). Patients with either partial remission (PR) or stable disease (SD) underwent nephrectomy followed by IFN-α maintenance at 3 x 9 x 106 IU/wk. Patients were evaluated with regard to age, sex, metastatic sites, morbidity, response, nephrectomy rate, time to progression and survival. RESULTS: Thirteen patients received 2 months of preoperative IFN-α; 3 stopped during the 2 months period due to progressive disease (PD). Eight patients developed either a PR (n=3) or SD (n=5) at metastatic sites and underwent nephrectomy. Survival at 1 year is 50% (4/8 patients). Median progression-free survival was 6 months (3-17 months).Two of the 3 patients with PR developed a CR after 2 months maintenance following surgery. Eight patients with PD did not undergo surgery and had a median survival of 4 months (range 1-8 months). CONCLUSIONS: Absence of progression at metastatic sites following IFN-α with the primary tumour in place may be used as selection for nephrectomy in patients with an intermediate prognosis. Currently, a randomised study is underway to assess the role of initial versus delayed nephrectomy in combination with IFN-α with regard to morbidity and survival.
939
940
RADICAL NEPHRECTOMY AND METASTATECTOMY COMBINED WITH IMMUNOTHERAPY FOR METASTATIC RENAL CELL CARCINOMA Park Y.H.1, Jeong C.W.1, Hong S.K.2, Jeong H.3, Kwak C.1, Lee E.1, Lee S.E.2 1 Seoul National University Hospital, Department of Urology, Seoul, South Korea, 2 Seoul National University Bundang Hospital, Department of Urology, Gyeonggi, South Korea, 3Seoul National University Boramae Hospital, Department of Urology, Seoul, South Korea INTRODUCTION & OBJECTIVES: To analyze the long-term efficacy of surgical treatment combined with immunotherapy as treatment for metastatic renal cell carcinoma (RCC). MATERIAL & METHODS: In this retrospective study, we reviewed the medical records of 145 patients who received immunotherapy (monotherapy with interferonα or combination therapy with interferon-α, interleukin-2 and 5-fluorouracil) for metastatic RCC at our hospital between May 1990 and July 2004.We assessed the objective response rates and overall survival according to the surgical treatment. Predictive factors for prolonged survival were identified by multivariate analysis. RESULTS: Median follow-up duration was 39.6 months (0-197). Overall response rate of total 145 patients was 19.1% (complete remission 16.0%, partial remission 3.1%) and median overall survival was 46 months (1-156). Treatment groups were: group A (n=67), radical nephrectomy and metastatectomy; group B (n=61), radical nephrectomy only; group C (n=17), no surgical treatment. There were no significant differences of demographic data and final pathological stage between three groups. Treatment group A, B, and C yielded objective response rates of 55.2%, 29.5%, and 5.9% (p<0.001), respectively. Group A (median overall survival, 58 months) showed a significantly improved overall survival compared with group B (median overall survival, 28 months; p=0.01) and group C (median overall survival, 13 months; p=0.0007). In group A and B, 5-year overall survival rate was 48.7% and 19.1% (p=0.01), respectively. Prolonged survival was associated with the number of organs with metastasis (one versus two or more) (p=0.001, HR=2.436), the time to metastasis (1 year or less versus more than 1year) (p=0.015, HR=2.151), nephrectomy status (p=0.04, HR=1.853), and metastatectomy status (p=0.04, HR=1.706) by multivariate analysis. CONCLUSIONS: For the management of metastatic RCC, surgical resection of primary and metastatic lesions combined with immunotherapy can prolong survival in selected patients.
WITH INCREASING TUMOUR SIZE HISTOPATHOLOGICAL FEATURES ARE MORE AGGRESSIVE IN CLEAR CELL RCC, BUT NOT IN PAPILLARY RCC Remzi M.1, Seitz C.1, Özsoy M.1, Tanovic E.2, Klingler H.C.1, Susani M.2, Dobrovits M.1, Faikovic H.1, Marberger M.1 1
Medical University of Vienna, of Urology, Vienna, Austria, 2Medical University of Vienna, of Pathology, Vienna, Austria INTRODUCTION & OBJECTIVES: Preoperative tumour size is a known risk factor in kidney tumours for more aggressive histopathological features, but data for different RCC subtypes are lacking. MATERIAL & METHODS: From 9/1994 to 9/2004 614 renal masses in adults were treated surgically. We retrospectively reviewed these for pathological findings and correlated histopathological features and renal cell carcinoma (RCC) subtypes with tumour size. For pathological staging and grading the 1997 TNM classification and Fuhrman classification were used, respectively. For further analyses all other RCC but papillary (pRCC) and clear cell RCC (ccRCC) were excluded, because low number of cases and therefore low statistical power. RESULTS: Mean tumour-size and patient age was 5.09±2.87cm and 62±13.5years, respectively. Overall renal cell cancer (RCC) was found in 510 tumours (83.1%). The rate of RCC was significant higher in tumours >4cm (86.5%) compared to tumours ≤ 4cm (79.2%) (p=0.0278), and increased in regression analysis (p=0.0302). Overall pT1, pT2, pT3a, pT3b, pT3c, and pT4 RCC was found in 42.3%, 16.9%, 27.8%, 10.0%, 0.2%, and 2.8%, respectively. Percentages of advanced stages (≥pT3a) were significantly higher with tumour size (p<0.001), as well as in the >4cm group (p<0.001). 375 (73.5%) were ccRCC and 82 (16.0%) pRCC. Overall Fuhrman G1, G2, G3, and G4 RCC were found in 10.6%, 62.8%, 21.1% and 5.5%, respectively. Percentages of advanced grading (G3/G4) were significantly higher with tumour size (p<0.001), as well as in the >4cm group (p<0.001) for clear cell RCC, but not for papillary RCC (Table 1). Lower percentage of papillary and a significant higher percentage of clear cell type RCC were found in small renal masses (≤4cm) compared to larger tumours (>4cm) (p<0.001). Nevertheless with increasing tumour size the risk to be primary metastasised was significant for clear cell RCC (0.0024), but nor for papillary RCC (0.7439).
N
Mean tumour size (cm)
Size ≤4cm
Multifocal
pT1
≥pT3a
M+
G1/G2
G3/G4
ccRCC
375
5.4±2.8
43.0%
10.7%
49.8%
45.0%
13.1%
73.1%
26.9%
pRCC
82
4.5±2.7
57.3%
25.9%
63.4%
26.8%
5.3%
80.4%
19.6%
0.0025
0.0170
0.0003
0.0130
0.0021
0.0231
0.0402
0.0412
p-value
CONCLUSIONS: With increasing tumour size the risk for higher Fuhrman grade G3/G4 and to be primary metastasized significantly increases in clear cell, but not papillary RCC.
Eur Urol Suppl 2006;5(2):257
938
IS THERE STILL A ROLE FOR HAND-ASSISTED LAPAROSCOPIC NEPHRECTOMY (HAL)?
INTERFERON ALPHA-2B AS MEDICAL SELECTION FOR NEPHRECTOMY IN PATIENTS WITH SYNCHRONOUS METASTATIC RENAL CELL CARCINOMA: A CONSECUTIVE STUDY
Appanna T.1, Martindale A.1, Goad J.1, Temelcos C.1, Clarke A.1, Asopa R.1, Cleeve L.2, Niall O.1
Bex A.1, Kerst M.2, Mallo H.2, Meinhardt W.1, Horenblas S.1, De Gast G.2
1
1
INTRODUCTION & OBJECTIVES: We have been performing laparoscopic nephrectomies since 2002 and have used the hand assisted technique on a regular basis. In light of the increasing demand for minimally invasive techniques in urology, we aim to report our results and to comment on the use of the hand port and its implications for the patient and on training.
INTRODUCTION & OBJECTIVES: Up to 25% of the patients with synchronous metastatic renal cell carcinoma (mRCC) treated with nephrectomy and interferon alpha-2b (IFN-α) will progress rapidly at metastatic sites and undergo needless surgery for an asymptomatic primary. We reversed the timing of surgery and immunotherapy and evaluated the role of initial IFN-α as selection for nephrectomy.
St. Vincent’s Hospital, Department of Urology, University of Melbourne, Melbourne, Australia, 2Melbourne Urology Group, Department of Urology, Melbourne, Australia
MATERIAL & METHODS: A combination of retrospective and prospective data collection was used to obtain patient demographics, operative details, pathology information and outcome data for all patients who underwent laparoscopic nephrectomy between April 2002 and June 2005 at St. Vincent’s Hospital and the Melbourne Urology Group in Melbourne, Australia. RESULTS: We performed 78 laparoscopic nephrectomies (47 of which were hand assisted) in the specified time period on patients with a mean age of 63.4 years. 38% of the public patients were operated on by a trainee/fellow as the primary surgeon and the median operating time was 180 mins. No differences were observed between pure and hand assisted laparoscopy (HAL) in terms of operative mortality and morbidity, in patient stay and analgesic use. CONCLUSIONS: Our results are in keeping with those of other published series. We have found the hand port to be a safe and effective tool for nephrectomy without the inherent risks of pure laparoscopy. As an incision is required to remove the kidney from the abdomen it seems illogical not to utilise that incision from the beginning of the case. The benefits are safer port placement, tactile feedback and early control of heavy bleeding. In addition trainees can rapidly get to grips with the technique. We would therefore advocate its use in all extirpative renal surgery and challenge the view that it is an inferior technique to pure laparoscopy.
The Netherlands Cancer Institute, Urology, Amsterdam, The Netherlands, 2The Netherlands Cancer Institute, Oncology, Amsterdam, The Netherlands
MATERIAL & METHODS: Sixteen patients with mRCC and the primary insitu received initial IFN-α for 8 weeks (2 weeks 5 x 3 x 106 IU/wk; 2 weeks 5 x 6 x 106 IU/wk; 2 weeks 5 x 9 x 106 IU/wk and 2 weeks 3 x 9 x 106 IU/wk). Patients with either partial remission (PR) or stable disease (SD) underwent nephrectomy followed by IFN-α maintenance at 3 x 9 x 106 IU/wk. Patients were evaluated with regard to age, sex, metastatic sites, morbidity, response, nephrectomy rate, time to progression and survival. RESULTS: Thirteen patients received 2 months of preoperative IFN-α; 3 stopped during the 2 months period due to progressive disease (PD). Eight patients developed either a PR (n=3) or SD (n=5) at metastatic sites and underwent nephrectomy. Survival at 1 year is 50% (4/8 patients). Median progression-free survival was 6 months (3-17 months).Two of the 3 patients with PR developed a CR after 2 months maintenance following surgery. Eight patients with PD did not undergo surgery and had a median survival of 4 months (range 1-8 months). CONCLUSIONS: Absence of progression at metastatic sites following IFN-α with the primary tumour in place may be used as selection for nephrectomy in patients with an intermediate prognosis. Currently, a randomised study is underway to assess the role of initial versus delayed nephrectomy in combination with IFN-α with regard to morbidity and survival.
939
940
RADICAL NEPHRECTOMY AND METASTATECTOMY COMBINED WITH IMMUNOTHERAPY FOR METASTATIC RENAL CELL CARCINOMA Park Y.H.1, Jeong C.W.1, Hong S.K.2, Jeong H.3, Kwak C.1, Lee E.1, Lee S.E.2 1 Seoul National University Hospital, Department of Urology, Seoul, South Korea, 2 Seoul National University Bundang Hospital, Department of Urology, Gyeonggi, South Korea, 3Seoul National University Boramae Hospital, Department of Urology, Seoul, South Korea INTRODUCTION & OBJECTIVES: To analyze the long-term efficacy of surgical treatment combined with immunotherapy as treatment for metastatic renal cell carcinoma (RCC). MATERIAL & METHODS: In this retrospective study, we reviewed the medical records of 145 patients who received immunotherapy (monotherapy with interferonα or combination therapy with interferon-α, interleukin-2 and 5-fluorouracil) for metastatic RCC at our hospital between May 1990 and July 2004.We assessed the objective response rates and overall survival according to the surgical treatment. Predictive factors for prolonged survival were identified by multivariate analysis. RESULTS: Median follow-up duration was 39.6 months (0-197). Overall response rate of total 145 patients was 19.1% (complete remission 16.0%, partial remission 3.1%) and median overall survival was 46 months (1-156). Treatment groups were: group A (n=67), radical nephrectomy and metastatectomy; group B (n=61), radical nephrectomy only; group C (n=17), no surgical treatment. There were no significant differences of demographic data and final pathological stage between three groups. Treatment group A, B, and C yielded objective response rates of 55.2%, 29.5%, and 5.9% (p<0.001), respectively. Group A (median overall survival, 58 months) showed a significantly improved overall survival compared with group B (median overall survival, 28 months; p=0.01) and group C (median overall survival, 13 months; p=0.0007). In group A and B, 5-year overall survival rate was 48.7% and 19.1% (p=0.01), respectively. Prolonged survival was associated with the number of organs with metastasis (one versus two or more) (p=0.001, HR=2.436), the time to metastasis (1 year or less versus more than 1year) (p=0.015, HR=2.151), nephrectomy status (p=0.04, HR=1.853), and metastatectomy status (p=0.04, HR=1.706) by multivariate analysis. CONCLUSIONS: For the management of metastatic RCC, surgical resection of primary and metastatic lesions combined with immunotherapy can prolong survival in selected patients.
WITH INCREASING TUMOUR SIZE HISTOPATHOLOGICAL FEATURES ARE MORE AGGRESSIVE IN CLEAR CELL RCC, BUT NOT IN PAPILLARY RCC Remzi M.1, Seitz C.1, Özsoy M.1, Tanovic E.2, Klingler H.C.1, Susani M.2, Dobrovits M.1, Faikovic H.1, Marberger M.1 1
Medical University of Vienna, of Urology, Vienna, Austria, 2Medical University of Vienna, of Pathology, Vienna, Austria INTRODUCTION & OBJECTIVES: Preoperative tumour size is a known risk factor in kidney tumours for more aggressive histopathological features, but data for different RCC subtypes are lacking. MATERIAL & METHODS: From 9/1994 to 9/2004 614 renal masses in adults were treated surgically. We retrospectively reviewed these for pathological findings and correlated histopathological features and renal cell carcinoma (RCC) subtypes with tumour size. For pathological staging and grading the 1997 TNM classification and Fuhrman classification were used, respectively. For further analyses all other RCC but papillary (pRCC) and clear cell RCC (ccRCC) were excluded, because low number of cases and therefore low statistical power. RESULTS: Mean tumour-size and patient age was 5.09±2.87cm and 62±13.5years, respectively. Overall renal cell cancer (RCC) was found in 510 tumours (83.1%). The rate of RCC was significant higher in tumours >4cm (86.5%) compared to tumours ≤ 4cm (79.2%) (p=0.0278), and increased in regression analysis (p=0.0302). Overall pT1, pT2, pT3a, pT3b, pT3c, and pT4 RCC was found in 42.3%, 16.9%, 27.8%, 10.0%, 0.2%, and 2.8%, respectively. Percentages of advanced stages (≥pT3a) were significantly higher with tumour size (p<0.001), as well as in the >4cm group (p<0.001). 375 (73.5%) were ccRCC and 82 (16.0%) pRCC. Overall Fuhrman G1, G2, G3, and G4 RCC were found in 10.6%, 62.8%, 21.1% and 5.5%, respectively. Percentages of advanced grading (G3/G4) were significantly higher with tumour size (p<0.001), as well as in the >4cm group (p<0.001) for clear cell RCC, but not for papillary RCC (Table 1). Lower percentage of papillary and a significant higher percentage of clear cell type RCC were found in small renal masses (≤4cm) compared to larger tumours (>4cm) (p<0.001). Nevertheless with increasing tumour size the risk to be primary metastasised was significant for clear cell RCC (0.0024), but nor for papillary RCC (0.7439).
N
Mean tumour size (cm)
Size ≤4cm
Multifocal
pT1
≥pT3a
M+
G1/G2
G3/G4
ccRCC
375
5.4±2.8
43.0%
10.7%
49.8%
45.0%
13.1%
73.1%
26.9%
pRCC
82
4.5±2.7
57.3%
25.9%
63.4%
26.8%
5.3%
80.4%
19.6%
0.0025
0.0170
0.0003
0.0130
0.0021
0.0231
0.0402
0.0412
p-value
CONCLUSIONS: With increasing tumour size the risk for higher Fuhrman grade G3/G4 and to be primary metastasized significantly increases in clear cell, but not papillary RCC.
Eur Urol Suppl 2006;5(2):257