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Papers by Allan Pantuck

The Journal of …, 2009

PURPOSE: We assessed CA9 single nucleotide polymorphisms and mutations, and their association wit... more PURPOSE: We assessed CA9 single nucleotide polymorphisms and mutations, and their association with CAIX protein expression, overall survival and response to interleukin-2 in white patients with metastatic clear cell renal cell carcinoma. MATERIALS METHODS: ...

The Journal of …, 2009

PURPOSE: We assessed CA9 single nucleotide polymorphisms and mutations, and their association wit... more PURPOSE: We assessed CA9 single nucleotide polymorphisms and mutations, and their association with CAIX protein expression, overall survival and response to interleukin-2 in white patients with metastatic clear cell renal cell carcinoma. MATERIALS METHODS: ...

Tony Burke, ed., Ancient Gospel or Modern Forgery? The Secret Gospel of Mark in Debate (Cascade Books), 101-34., 2013

The Journal of Urology, 2008

We characterized the clinicopathological features and the prognosis of small solid renal tumors d... more We characterized the clinicopathological features and the prognosis of small solid renal tumors defined as tumors 4 cm or smaller. Materials and Methods: We identified 1,208 patients who were treated with nephrectomy at 5 international academic centers for small solid renal tumors. Clinicopathological parameters and outcome data were collected for each patient and analyzed. Results: Of the tumors 88% were renal cell carcinoma and 12% were benign. Of those with renal cell carcinoma 995 (93%) were localized (N0M0) and 72 (7%) presented with metastatic disease. Tumor size did not predict synchronous metastatic disease. The incidence of metastatic disease in the tumor size ranges 0.1 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 cm was 7%, 6%, 5% and 8%, respectively (p ϭ 0.322). Survival rates were excellent. The majority of patients who died of renal cell carcinoma (54%) presented with synchronous metastatic disease, but 3% of patients with localized disease also died of renal cell carcinoma. In patients with localized disease there was a 7% chance of recurrence post nephrectomy at 5 years. Progression-free survival (28 months) was better than for patients with metastatic disease having a primary tumor greater than 4 cm (8 months). Tumor size was not retained as an independent prognostic factor of survival in multivariate analyses. The University of California Integrated Staging System and the Karakiewicz nomogram were the best predictors of cancer specific survival for all renal cell carcinoma stages (c-index 0.87). Conclusions: More than 85% of small solid renal tumors are renal cell carcinoma. The majority of localized small renal tumors can be cured with existing surgical approaches. However, there is a small but not insignificant risk of synchronous and metachronous metastatic disease and cancer associated death. Patients considering experimental therapies such as ablation and surveillance should be aware of this. Tumor size alone is not sufficient to distinguish renal cell carcinoma with benign behavior from aggressive small renal cell carcinoma. Survival of patients with small metastatic renal cell carcinoma is better then expected. The biology of these unique tumors should be further studied.

Cancer, 2013

BACKGROUND: The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau (VHL) tumor suppress... more BACKGROUND: The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau (VHL) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia-inducible factor 1a (HIF-1a) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1a gene) in clear cell renal cell carcinoma (ccRCC). METHODS: In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL þ3p/þ14q (VHL wild type [VHL-WT]), VHL þ3p/À14q (VHL-WT plus HIF2a [WT/H2]), À3p/þ14q (HIF1a and HIF2a [H1H2]), and À3p/À14q (HIF2a [H2]). RESULTS: Among patients who had loss of 3p, tumors with À3p/ À14q (H2) alterations were larger (P ¼ .002), had higher grade (P ¼ .002) and stage (P ¼ .001), and more often were metastatic (P ¼ .029) than tumors that retained 14q (H1H2). All patients who had tumors with À3p/À14q (H2) had worse cancer-specific survival (P ¼ .014), and patients who had localized disease (P ¼ .012) and primary T1 (pT1) tumors (P ¼ .008) had worse recurrence-free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence-free survival (hazard ratio, 11.19; 95% confidence interval, 1.91-65.63) and cancer-specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09-82.16). The current investigation was limited by its retrospective design, single-center experience, and a lack of confirmatory protein analyses. CONCLU-SIONS: Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1a gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1a functions as an important tumor suppressor gene in ccRCC. Cancer ;000:000-000. V C American Cancer Society.

The Lancet Oncology, 2015

Urologic oncology, Jan 27, 2015

With a limited number of prognostic and predictive biomarkers available, carbonic anhydrase-IX (C... more With a limited number of prognostic and predictive biomarkers available, carbonic anhydrase-IX (CAIX) has served as an important prognostic biomarker for patients with clear cell renal cell carcinoma (ccRCC). However, studies have recently called into question the role of CAIX as a biomarker for ccRCC. To investigate this uncertainty, we quantified the association of CAIX with lymphatic involvement and survival using data from ARISER study (WX-2007-03-HR)-a prospective trial involving subjects with high-risk nonmetastatic ccRCC. We reviewed the records of 813 patients enrolled in the ARISER study. Central review of histology, grade, and CAIX staining (frequency and intensity) was performed. CAIX score was derived by multiplying the staining intensity (1-3) by percent positive cells (0%-100%), yielding a range of 0 to 300. We quantified the association of CAIX expression and score with lymphatic spread and survival (disease-free survival [DFS] and overall survival [OS]) using Kaplan-...

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 15, 2003

Historically, clinical factors have been used as prognostic markers for patients with renal cell ... more Historically, clinical factors have been used as prognostic markers for patients with renal cell carcinoma (RCC). Recent advances in the understanding of the pathogenesis, behavior, and molecular biology of RCC have paved the way for developments that may enhance early diagnosis, better predict tumor prognosis, and improve survival for RCC patients. This report reviews the molecular mechanisms of the hypoxia-induced pathway that play an essential role in angiogenesis, glycolysis, and apoptosis of common cancers and may be responsible for the ability of the cancers to adapt to a hypoxic environment and also for their resistance to radiation and chemotherapy. The hypoxia-induced pathway has been linked genetically to RCC through the von Hippel-Lindau tumor suppressor gene, which is inactivated in a majority of clear cell RCCs. Therefore, RCC is a particularly attractive clinical model to exploit the hypoxia-induced pathway for new therapeutic interventions. von Hippel-Lindau, hypoxia ...

Cancer, Jan 15, 2003

The current study was performed to determine the impact of the presence of retroperitoneal lympha... more The current study was performed to determine the impact of the presence of retroperitoneal lymphadenopathy on the survival and response to immunotherapy of patients with metastatic renal cell carcinoma (RCC). A retrospective cohort study was performed with outcome assessment based on the chart review of demographic, clinical, and pathologic data from 1087 patients. Patients with RCC who did not present with metastatic disease, who did not undergo nephrectomy as part of their cancer treatment, and those in whom either the lymph node (N) or metastatic (M) status was unknown, were excluded. A total of 322 M1 patients who met these criteria and who underwent nephrectomy for unilateral RCC formed the principal study population. Two hundred thirty-six patients presented with N0M1 disease and 86 patients presented with N+M1 disease. In M1 patients, the presence of positive regional lymph nodes was associated with larger sized, higher grade, locally advanced primary tumors that were more co...

The Journal of urology, 2003

We better defined the benefits and morbidity of lymph node dissection in patients with localized ... more We better defined the benefits and morbidity of lymph node dissection in patients with localized renal cell carcinoma using the experience of patients treated at our institution. A retrospective cohort study was performed with outcome assessment based on the chart review of demographic, clinical and pathological data in 1,087 patients with renal cell carcinoma treated at our institution. Patients with renal cell carcinoma who did not undergo nephrectomy as part of cancer treatment, those with bilateral disease and those for whom nodal status was unknown were not included in this study. A total of 900 patients meeting these criteria who underwent nephrectomy for unilateral renal cell carcinoma at our medical center form the principal study population. Positive lymph nodes were associated with larger, higher grade, locally advanced primary tumors that were more commonly associated with sarcomatoid features. Positive nodes were 3 to 4 times more common in patients with metastatic disea...

Urology, 2002

To describe an open technique for the cryosurgical ablation of small renal tumors using multiple ... more To describe an open technique for the cryosurgical ablation of small renal tumors using multiple ultrathin cryoprobes. Renal cryosurgery is an evolving surgical technique, and uncertainties exist regarding the ideal approach to freezing renal tumors. Using an open surgical approach, a 3-cm upper pole renal mass was ablated using five, state-of-the-art, 1.5-mm cryoprobes simultaneously under real-time ultrasound guidance. The technique is described and demonstrated in a multisegment, Internet-based video tutorial. The blood loss was minimal, and no intraoperative or postoperative complications were experienced. Follow-up imaging at 3 months suggested shrunken, nonviable tumor. Cryosurgical ablation of renal tumors using multiple 1.5-mm cryoprobes is a safe, feasible approach that may be associated with a decreased risk of bleeding.

European Urology Supplements, 2005

Journal of vascular and interventional radiology : JVIR, 2014

To determine oncologic outcomes and predictors of primary efficacy, including RENAL nephrometry s... more To determine oncologic outcomes and predictors of primary efficacy, including RENAL nephrometry scores (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines), after percutaneous radiofrequency (RF) ablation of proven renal cell carcinoma (RCC). Patients who underwent percutaneous computed tomography- and ultrasound-guided RF ablation for histologically proven RCC from 2004 to 2011 were evaluated. Clinical data, pathologic findings, technical details, and outcomes were reviewed. Univariate and multivariate logistic regression analysis was performed to determine predictors of primary technique effectiveness and complications. Local tumor progression-free, metastasis-free, and overall survival were calculated. One hundred RCC lesions underwent 115 RF ablation sessions in 84 patients. Median follow-up was 24 months (mean, 27 mo; range, 1-106 mo). Efficacy of RF ablation was defined per Internationa...

Clinical cancer research : an official journal of the American Association for Cancer Research, 2015

High-dose aldesleukin (HD IL2) received FDA approval for the treatment of metastatic renal cell c... more High-dose aldesleukin (HD IL2) received FDA approval for the treatment of metastatic renal cell carcinoma (MRCC) in 1992, producing a 14% objective response rate (ORR) and durable remissions. Retrospective studies suggested that clinical and pathologic features could predict for benefit. The Cytokine Working Group conducted this prospective trial to validate proposed predictive markers of response to HD IL2. Standard HD IL2 was administered to prospectively evaluate whether the ORR of patients with mRCC with "good" predictive pathologic features based on an "integrated selection" model [ISM (e.g., clear-cell histology subclassification and carbonic anhydrase-9 (CA-9) IHC staining] was significantly higher than the ORR of a historical, unselected population. Archived tumor was collected for pathologic analysis including tumor programmed death-ligand 1 (PD-L1) expression. One hundred and twenty eligible patients were enrolled between June 11 and September 7; 70% we...

Urologic Oncology: Seminars and Original Investigations, 2015

Accurate postoperative stratification of patients with renal cell carcinoma (RCC) in distinct pro... more Accurate postoperative stratification of patients with renal cell carcinoma (RCC) in distinct prognostic groups is essential for tailoring follow-up, medical therapy, and inclusion in clinical trials. Increasing evidence suggests that Onodera׳s prognostic nutritional index (PNI) is a stage- and grade-independent predictor of poor outcomes in patients with cancer, but there are no data in RCC. We reviewed medical records of 1,344 patients with RCC who underwent radical or partial nephrectomy at the Medical University of Vienna and the University of California-Los Angeles between 1991 and 2012. Associations with cancer-specific survival were assessed with univariable and multivariable Cox proportional hazards models. Discrimination was measured with the C-index. The median postoperative follow-up was 40 months. An increase of PNI by 1 unit was associated with a decrease in the risk of death from RCC by 7% (hazard ratio = 0.93, P<0.001). In multivariable analyses, the PNI was an independent prognostic factor (P<0.001). Adding the PNI improved the discrimination of a base model by 0.4%. The PNI is an independent prognostic factor in patients with RCC. Its use increases the accuracy of established prognostic factors. PNI may be a meaningful adjunct for tailoring surveillance, medical therapy, and clinical trial design.

Urologic oncology, 2014

To analyze to what extent partial nephrectomy (PN) is superior to radical nephrectomy (RN) in pre... more To analyze to what extent partial nephrectomy (PN) is superior to radical nephrectomy (RN) in preserving renal function outcome in relation to tumor size indication. Clinical data from 973 patients operated at 9 academic institutions were retrospectively analyzed. Glomerular filtration rate (GFR) before and after surgery was calculated with the abbreviated Modification of the Diet in Renal Disease equation. For a fair comparison between the 2 techniques, all imperative indications for PN were excluded. A shift to a less favorable GFR group following surgery was considered clinically significant. Median age at diagnosis was 60 years (19-91). Tumor size was smaller than 4 cm in 665 (68.3%) cases and larger than 4 cm in 308 (31.7%) cases. PN and RN were performed in 663 (68.1%) and 310 (31.9%) patients, respectively. In univariate analysis, patients undergoing PN had a smaller risk for developing significant GFR change following surgery than those undergoing RN did. This was true for t...

The Journal of …, 2009

PURPOSE: We assessed CA9 single nucleotide polymorphisms and mutations, and their association wit... more PURPOSE: We assessed CA9 single nucleotide polymorphisms and mutations, and their association with CAIX protein expression, overall survival and response to interleukin-2 in white patients with metastatic clear cell renal cell carcinoma. MATERIALS METHODS: ...

The Journal of …, 2009

PURPOSE: We assessed CA9 single nucleotide polymorphisms and mutations, and their association wit... more PURPOSE: We assessed CA9 single nucleotide polymorphisms and mutations, and their association with CAIX protein expression, overall survival and response to interleukin-2 in white patients with metastatic clear cell renal cell carcinoma. MATERIALS METHODS: ...

Tony Burke, ed., Ancient Gospel or Modern Forgery? The Secret Gospel of Mark in Debate (Cascade Books), 101-34., 2013

The Journal of Urology, 2008

We characterized the clinicopathological features and the prognosis of small solid renal tumors d... more We characterized the clinicopathological features and the prognosis of small solid renal tumors defined as tumors 4 cm or smaller. Materials and Methods: We identified 1,208 patients who were treated with nephrectomy at 5 international academic centers for small solid renal tumors. Clinicopathological parameters and outcome data were collected for each patient and analyzed. Results: Of the tumors 88% were renal cell carcinoma and 12% were benign. Of those with renal cell carcinoma 995 (93%) were localized (N0M0) and 72 (7%) presented with metastatic disease. Tumor size did not predict synchronous metastatic disease. The incidence of metastatic disease in the tumor size ranges 0.1 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 cm was 7%, 6%, 5% and 8%, respectively (p ϭ 0.322). Survival rates were excellent. The majority of patients who died of renal cell carcinoma (54%) presented with synchronous metastatic disease, but 3% of patients with localized disease also died of renal cell carcinoma. In patients with localized disease there was a 7% chance of recurrence post nephrectomy at 5 years. Progression-free survival (28 months) was better than for patients with metastatic disease having a primary tumor greater than 4 cm (8 months). Tumor size was not retained as an independent prognostic factor of survival in multivariate analyses. The University of California Integrated Staging System and the Karakiewicz nomogram were the best predictors of cancer specific survival for all renal cell carcinoma stages (c-index 0.87). Conclusions: More than 85% of small solid renal tumors are renal cell carcinoma. The majority of localized small renal tumors can be cured with existing surgical approaches. However, there is a small but not insignificant risk of synchronous and metachronous metastatic disease and cancer associated death. Patients considering experimental therapies such as ablation and surveillance should be aware of this. Tumor size alone is not sufficient to distinguish renal cell carcinoma with benign behavior from aggressive small renal cell carcinoma. Survival of patients with small metastatic renal cell carcinoma is better then expected. The biology of these unique tumors should be further studied.

Cancer, 2013

BACKGROUND: The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau (VHL) tumor suppress... more BACKGROUND: The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau (VHL) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia-inducible factor 1a (HIF-1a) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1a gene) in clear cell renal cell carcinoma (ccRCC). METHODS: In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL þ3p/þ14q (VHL wild type [VHL-WT]), VHL þ3p/À14q (VHL-WT plus HIF2a [WT/H2]), À3p/þ14q (HIF1a and HIF2a [H1H2]), and À3p/À14q (HIF2a [H2]). RESULTS: Among patients who had loss of 3p, tumors with À3p/ À14q (H2) alterations were larger (P ¼ .002), had higher grade (P ¼ .002) and stage (P ¼ .001), and more often were metastatic (P ¼ .029) than tumors that retained 14q (H1H2). All patients who had tumors with À3p/À14q (H2) had worse cancer-specific survival (P ¼ .014), and patients who had localized disease (P ¼ .012) and primary T1 (pT1) tumors (P ¼ .008) had worse recurrence-free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence-free survival (hazard ratio, 11.19; 95% confidence interval, 1.91-65.63) and cancer-specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09-82.16). The current investigation was limited by its retrospective design, single-center experience, and a lack of confirmatory protein analyses. CONCLU-SIONS: Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1a gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1a functions as an important tumor suppressor gene in ccRCC. Cancer ;000:000-000. V C American Cancer Society.

The Lancet Oncology, 2015

Urologic oncology, Jan 27, 2015

With a limited number of prognostic and predictive biomarkers available, carbonic anhydrase-IX (C... more With a limited number of prognostic and predictive biomarkers available, carbonic anhydrase-IX (CAIX) has served as an important prognostic biomarker for patients with clear cell renal cell carcinoma (ccRCC). However, studies have recently called into question the role of CAIX as a biomarker for ccRCC. To investigate this uncertainty, we quantified the association of CAIX with lymphatic involvement and survival using data from ARISER study (WX-2007-03-HR)-a prospective trial involving subjects with high-risk nonmetastatic ccRCC. We reviewed the records of 813 patients enrolled in the ARISER study. Central review of histology, grade, and CAIX staining (frequency and intensity) was performed. CAIX score was derived by multiplying the staining intensity (1-3) by percent positive cells (0%-100%), yielding a range of 0 to 300. We quantified the association of CAIX expression and score with lymphatic spread and survival (disease-free survival [DFS] and overall survival [OS]) using Kaplan-...

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 15, 2003

Historically, clinical factors have been used as prognostic markers for patients with renal cell ... more Historically, clinical factors have been used as prognostic markers for patients with renal cell carcinoma (RCC). Recent advances in the understanding of the pathogenesis, behavior, and molecular biology of RCC have paved the way for developments that may enhance early diagnosis, better predict tumor prognosis, and improve survival for RCC patients. This report reviews the molecular mechanisms of the hypoxia-induced pathway that play an essential role in angiogenesis, glycolysis, and apoptosis of common cancers and may be responsible for the ability of the cancers to adapt to a hypoxic environment and also for their resistance to radiation and chemotherapy. The hypoxia-induced pathway has been linked genetically to RCC through the von Hippel-Lindau tumor suppressor gene, which is inactivated in a majority of clear cell RCCs. Therefore, RCC is a particularly attractive clinical model to exploit the hypoxia-induced pathway for new therapeutic interventions. von Hippel-Lindau, hypoxia ...

Cancer, Jan 15, 2003

The current study was performed to determine the impact of the presence of retroperitoneal lympha... more The current study was performed to determine the impact of the presence of retroperitoneal lymphadenopathy on the survival and response to immunotherapy of patients with metastatic renal cell carcinoma (RCC). A retrospective cohort study was performed with outcome assessment based on the chart review of demographic, clinical, and pathologic data from 1087 patients. Patients with RCC who did not present with metastatic disease, who did not undergo nephrectomy as part of their cancer treatment, and those in whom either the lymph node (N) or metastatic (M) status was unknown, were excluded. A total of 322 M1 patients who met these criteria and who underwent nephrectomy for unilateral RCC formed the principal study population. Two hundred thirty-six patients presented with N0M1 disease and 86 patients presented with N+M1 disease. In M1 patients, the presence of positive regional lymph nodes was associated with larger sized, higher grade, locally advanced primary tumors that were more co...

The Journal of urology, 2003

We better defined the benefits and morbidity of lymph node dissection in patients with localized ... more We better defined the benefits and morbidity of lymph node dissection in patients with localized renal cell carcinoma using the experience of patients treated at our institution. A retrospective cohort study was performed with outcome assessment based on the chart review of demographic, clinical and pathological data in 1,087 patients with renal cell carcinoma treated at our institution. Patients with renal cell carcinoma who did not undergo nephrectomy as part of cancer treatment, those with bilateral disease and those for whom nodal status was unknown were not included in this study. A total of 900 patients meeting these criteria who underwent nephrectomy for unilateral renal cell carcinoma at our medical center form the principal study population. Positive lymph nodes were associated with larger, higher grade, locally advanced primary tumors that were more commonly associated with sarcomatoid features. Positive nodes were 3 to 4 times more common in patients with metastatic disea...

Urology, 2002

To describe an open technique for the cryosurgical ablation of small renal tumors using multiple ... more To describe an open technique for the cryosurgical ablation of small renal tumors using multiple ultrathin cryoprobes. Renal cryosurgery is an evolving surgical technique, and uncertainties exist regarding the ideal approach to freezing renal tumors. Using an open surgical approach, a 3-cm upper pole renal mass was ablated using five, state-of-the-art, 1.5-mm cryoprobes simultaneously under real-time ultrasound guidance. The technique is described and demonstrated in a multisegment, Internet-based video tutorial. The blood loss was minimal, and no intraoperative or postoperative complications were experienced. Follow-up imaging at 3 months suggested shrunken, nonviable tumor. Cryosurgical ablation of renal tumors using multiple 1.5-mm cryoprobes is a safe, feasible approach that may be associated with a decreased risk of bleeding.

European Urology Supplements, 2005

Journal of vascular and interventional radiology : JVIR, 2014

To determine oncologic outcomes and predictors of primary efficacy, including RENAL nephrometry s... more To determine oncologic outcomes and predictors of primary efficacy, including RENAL nephrometry scores (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines), after percutaneous radiofrequency (RF) ablation of proven renal cell carcinoma (RCC). Patients who underwent percutaneous computed tomography- and ultrasound-guided RF ablation for histologically proven RCC from 2004 to 2011 were evaluated. Clinical data, pathologic findings, technical details, and outcomes were reviewed. Univariate and multivariate logistic regression analysis was performed to determine predictors of primary technique effectiveness and complications. Local tumor progression-free, metastasis-free, and overall survival were calculated. One hundred RCC lesions underwent 115 RF ablation sessions in 84 patients. Median follow-up was 24 months (mean, 27 mo; range, 1-106 mo). Efficacy of RF ablation was defined per Internationa...

Clinical cancer research : an official journal of the American Association for Cancer Research, 2015

High-dose aldesleukin (HD IL2) received FDA approval for the treatment of metastatic renal cell c... more High-dose aldesleukin (HD IL2) received FDA approval for the treatment of metastatic renal cell carcinoma (MRCC) in 1992, producing a 14% objective response rate (ORR) and durable remissions. Retrospective studies suggested that clinical and pathologic features could predict for benefit. The Cytokine Working Group conducted this prospective trial to validate proposed predictive markers of response to HD IL2. Standard HD IL2 was administered to prospectively evaluate whether the ORR of patients with mRCC with "good" predictive pathologic features based on an "integrated selection" model [ISM (e.g., clear-cell histology subclassification and carbonic anhydrase-9 (CA-9) IHC staining] was significantly higher than the ORR of a historical, unselected population. Archived tumor was collected for pathologic analysis including tumor programmed death-ligand 1 (PD-L1) expression. One hundred and twenty eligible patients were enrolled between June 11 and September 7; 70% we...

Urologic Oncology: Seminars and Original Investigations, 2015

Accurate postoperative stratification of patients with renal cell carcinoma (RCC) in distinct pro... more Accurate postoperative stratification of patients with renal cell carcinoma (RCC) in distinct prognostic groups is essential for tailoring follow-up, medical therapy, and inclusion in clinical trials. Increasing evidence suggests that Onodera׳s prognostic nutritional index (PNI) is a stage- and grade-independent predictor of poor outcomes in patients with cancer, but there are no data in RCC. We reviewed medical records of 1,344 patients with RCC who underwent radical or partial nephrectomy at the Medical University of Vienna and the University of California-Los Angeles between 1991 and 2012. Associations with cancer-specific survival were assessed with univariable and multivariable Cox proportional hazards models. Discrimination was measured with the C-index. The median postoperative follow-up was 40 months. An increase of PNI by 1 unit was associated with a decrease in the risk of death from RCC by 7% (hazard ratio = 0.93, P<0.001). In multivariable analyses, the PNI was an independent prognostic factor (P<0.001). Adding the PNI improved the discrimination of a base model by 0.4%. The PNI is an independent prognostic factor in patients with RCC. Its use increases the accuracy of established prognostic factors. PNI may be a meaningful adjunct for tailoring surveillance, medical therapy, and clinical trial design.

Urologic oncology, 2014

To analyze to what extent partial nephrectomy (PN) is superior to radical nephrectomy (RN) in pre... more To analyze to what extent partial nephrectomy (PN) is superior to radical nephrectomy (RN) in preserving renal function outcome in relation to tumor size indication. Clinical data from 973 patients operated at 9 academic institutions were retrospectively analyzed. Glomerular filtration rate (GFR) before and after surgery was calculated with the abbreviated Modification of the Diet in Renal Disease equation. For a fair comparison between the 2 techniques, all imperative indications for PN were excluded. A shift to a less favorable GFR group following surgery was considered clinically significant. Median age at diagnosis was 60 years (19-91). Tumor size was smaller than 4 cm in 665 (68.3%) cases and larger than 4 cm in 308 (31.7%) cases. PN and RN were performed in 663 (68.1%) and 310 (31.9%) patients, respectively. In univariate analysis, patients undergoing PN had a smaller risk for developing significant GFR change following surgery than those undergoing RN did. This was true for t...