Monday, June 9, 2014

AUA Highlights: Kidney Cancer, by Dr. Pierorazio

Kidney cancer is one of the major diseases treated by urologists and urologic oncologists.  Kidney cancer was well represented at this year's 2014 American Urological Association (AUA) Annual Meeting in Orlando, Florida.  Kidney cancer had a major seat in the AUA plenary sessions and the Society of Urologic Oncology (SUO) Meeting.  In addition, the scientific sessions were well attended and lively discussion often ensued.  Here are some of the highlights and commentary from the meeting, click on the links below to see webcasts or read the abstracts:

During the AUA Plenary: CROSSFIRE - CONTROVERSIES IN UROLOGY, kidney cancer thought-leaders Michael Jewett, Inderbir S. Gill, MD, MCh, Robert G. Uzzo, MD, Michael Blute, MD and John Libertino, MD debated "Minimally Invasive Partial Nephrectomy is the New Gold Standard for Renal Cancer."  (Follow the link above or click here to see the debate)  In general, the debate lacked strong evidence and was an endorsement of expert opinions.  However, Dr. Uzzo did an excellent job and laid out the argument, showing that while no Level 1 Evidence exists comparing minimally-invasive and open Partial Nephrectomy (PN), population-based data demonstrates an ever-increasing use of minimally-invasive surgery (MIS) and improved perioperative outcomes (length of stay, decreased blood loss and lower complications) for MIS.  However, oncologic outcomes (most importantly margin rates and cancer-specific survival) are equivalent between the two approaches.  Drs. Blute and Libertino argued for the continued use of open PN, citing the equivalent oncologic outcomes.  My take home was: there is a role for both minimally-invasive and open partial nephrectomy.  Outcomes are similar and the surgeon should perform the best operation for that given patient and tumor.

In the SUO Meeting, topics ranged from clinically localized to metastatic kidney cancer.  A major topic of focus at this meeting and throughout the week was clinical heterogeneity in kidney cancer. James Hsieh, MD, PhD, laid out an elegant argument for a "River Model" instead of "Branched Evolution" (akin to a tree) for the genetic evolution of kidney tumors.  He argued that as kidney tumors grow and progress, the genetics diverge and converge along several pathways, instead of following a number of linear progressions.  Other topics of interest including percutaneous renal mass biopsy and the treatment of metastatic disease.  Dr. Jewett discussed biopsy for all patients demonstrating a 94% concordance rate of low-grade renal cell carcinoma (RCC) in their Canadian series.  While these concordance rates are promising, they should be taken with consideration that most patients with small renal masses have low-grade tumors and therefore these numbers are skewed to predict insignificant disease.  In contrast, Dr. Uzzo argued for a more thoughtful approach and biopsy in only those patients in whom it would change mangement.  With regard to metastatic cancer, Dr. Figlin laid out a thoughtful paradigm for the treatment of advanced cancers based on objective response to systemic therapy, rather than picking from the list of options currently advocated by groups like the National Comprehensive Cancer Network (NCCN).


A number of posters and podiums focused on the biologic boundaries of renal cell carcinoma and its implications for positive surgical margins, enucleation and cancer control.  Alessandro Volpe and colleagues from Milan, Italy demonstrated that 40-50% of RCC invade the pseudocapsule and those tumors had a worse prognosis.  A group from Germany found that patients with a margin of 1mm or less had a higher rate of disease recurrence and kidney cancer death.  Finally, Dr. Ronald Boris and colleagues from Indiana looked at patients with clear-cell RCC and the complete tumor capsule and surrounding inflammation around the tumor.  They found that RCC rarely demonstrated capsular invasion, however found "gaps" in the tumor capsule gaps more often in late stages indicating there may be a loss of immune “control” over capsular penetration when elucidating the aggressive behavior of advanced ccRCC.

PD10-06: Classification of pseudocapsular invasion in organ-confined renal cell carcinoma: correlation with histological variables and prognostic impact.  Alessandro Volpe*, Antonia Di Domenico, Novara, Italy, Enrico Bollito, Turin, Italy, Cristina Bozzola, Novara, Italy, Riccardo Bertolo, Turin, Italy, Luisa Zegna, Paolo De Angelis, Novara, Italy, Daniele Amparore, Francesco Porpiglia, Turin, Italy, Carlo Terrone, Novara, Italy
PD10-08: Prognostic impact of tumor surrounding renal parenchyma in nephron sparing surgery – Is simple enucleation really enough? Stefan Aufderklamm*, Jörg Hennenlotter, Tilman Todenhöfer, Nicolas Senghaas, Georgios Gakis, Marcus Scharpf, Arnulf Stenzl, Christian Schwentner, Tuebingen, Germany
MP30-21: Pathologic variances in tumor capsule properties of clear cell renal cell carcinoma across various clinical stages Joseph M. Jacob*, Dibson D. Gondim, Jose A. Pedrosa, Muhammad T. Idrees, Ronald S. Boris, Indianapolis, IN


Active surveillance (AS) was a hot topic given the recent questions of overtreatment in other diseases like prostate cancer.  The Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry is a multi-institutional study led by Johns Hopkins, that has followed nearly 200 patients over the past 5 years.  Six abstracts demonstrated results from DISSRM:

  • PD10-09: DISSRM Score is an objective scoring system composed of age, ECOG performance status, tumor size, tumor complexity (RENAL Nephrometry) and Cardiovascular Index that identifies patients most suitable for AS.
  • MP54-03: The 1st surveillance image for patients on AS can lead to highly variable growth rates.  Over the course of a year or more, most patients demonstrate a slow growth rate (approximately 1mm/year), however this can be grossly overestimated by the high-variability of GR in the first image within a few months of starting surveillance.  Hear the webcast at UroToday.
  • MP54-04: Patients on AS have a decreasing GFR equivalent to patients undergoing PN, while both were superior to Radical Nephrectomy (RN).  It appeared that renal function was unaffected by tumor size or GR, however should be considered when choosing a management strategy.
  • MP54-05: Quality-of-life was not adversely affected for patients on AS; in fact they had worse perception of physical health (reflecting their increased comorbidities and advanced age), but no change in mental health over time.
  • MP64-09: In this analysis, tumors close to the renal hilum and collecting system had higher growth rates that other tumors, perhaps indicating more aggressive tumors, but at a minimum providing expectations for patients undergoing AS.
  • PD17-06: With a median follow-up of 2 years, but a maximum of 5 years, the overall survival was equivalent among patients undergoing immediate treatment of AS. No patients undergoing AS died of kidney cancer.
Other groups also looked at AS cohorts: 
  • PD17-04, PD17-05: Dr. Mehrazin and colleagues from Fox Chase looked at their AS experience and found that complex tumors were more likely to grow rapidly and examined outcomes for their patients with larger, cT1b renal tumors.  They found similar growth kinetics for larger and smaller tumors.  They found 34% of patients underwent surgery, but no patients died of kidney cancer.
  • MP59-20: Dr. Dorin and colleageus looked at a conglomerate of small renal and complex cystic masses and found low growth rates and progression.  They found that GR decreased with increasing mass size and a 35% rate of intervention at 10-years.
PD10-09: The DISSRM Score: Objective Scoring System Identifies Patients with Small Renal Masses Most Suitable for Active Surveillance.  Phillip Pierorazio, Deborah Kaye*, Baltimore, MD, Matthew Danzig, Rashed Ghandour, New York, NY, Peter Chang, Robert Hartman, Andrew Wagner, Boston, MA, James McKiernan, New York, NY, Mohamad Allaf, Baltimore, MD
MP54-03: First Surveillance Image for Patients with a Small Renal Mass Should Not Determine Outcome: Results from the DISSRM Registry.  Phillip Pierorazio, Nathaniel Readal*, Baltimore, MD, Matthew Danzig, Rashed Ghandour, New York, NY, Peter Chang, Robert Hartman, Andrew Wagner, Boston, MA, James McKiernan, New York, NY, Mohamad Allaf, Baltimore, MD
MP54-04: Partial Nephrectomy is Equivalent to Active Surveillance in Preserving Renal Function for Patients with Small Renal Masses.  Matthew Danzig*, Rashed Ghandour, Srinath Kotamarti, Tina Schubert, Arindam RoyChoudhury, New York, NY, Phillip Pierorazio, Baltimore, MD, Ketan Badani, New York, NY, Mohamad Allaf, Baltimore, MD, James McKiernan, New York, NY
MP54-05: Mental Health Not Affected by Active Surveillance for Patients with Small Renal Masses: Quality of Life Results from the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry.  Phillip Pierorazio, Michael Gorin*, Baltimore, MD, Matthew Danzig, Rashed Ghandour, New York, NY, Peter Chang, Robert Hartman, Andrew Wagner, Boston, MA, James McKiernan, New York, NY, Mohamad Allaf, Baltimore, MD
MP64-09: Prospective Analysis of Tumor Growth Rates Based on Patient Comorbidities and Imaging Characteristics from the DISSRM Registry: Implications for Future Nephron-Sparing Surgery.  Phillip Pierorazio, Mark Ball*, Baltimore, MD, Matthew Danzig, Rashed Ghandour, New York, NY, Peter Chang, Robert Hartman, Andrew Wagner, Boston, MA, James McKiernan, New York, NY, Mohamad Allaf, Baltimore, MD
PD17-06: Active surveillance for small renal masses non-inferior to primary intervention: 5-year analysis of the multi-institutional, prospective DISSRM (delayed intervention and surveillance for small renal masses) Registry.  Phillip Pierorazio, Mark Ball*, Baltimore, MD, Matthew Danzig, Rashed Ghandour, New York, NY, Peter Chang, Robert Hartman, Andrew Wagner, Boston, MA, James McKiernan, New York, NY, Mohamad Allaf, Baltimore, MD
PD17-04: EXPERIENCE WITH ACTIVE SURVEILLANCE (AS) IN PATIENTS WITH RENAL MASS >4cm: ASSESSMENT OF GROWTH KINETICS AND OUTCOMES.  Reza Mehrazin*, Marc C. Smaldone, Alexander Kutikov, Jeffrey J. Tomaszewski, Tianyu Li, Timothy Ito, Philip Abbosh, Rosalia Viterbo, Richard E. Greenberg, David Y.T. Chen, Robert G. Uzzo, Philadelphia, PA
PD17-05: Tumor Anatomic Complexity Predicts Growth Kinetics of Renal Masses Under Active Surveillance.  Reza Mehrazin*, Marc C. Smaldone, Brian Egleston, Charlie Concodora, Jeffrey J. Tomaszewski, Philip Abbosh, Timothy Ito, Jason Lomboy, Alexander Chow, Rosalia Viterbo, Richard E. Greenberg, David Y.T. Chen, Alexander Kutikov, Robert G. Uzzo, Philadelphia, PA
MP59-20: Active Surveillance of Renal Masses: An Analysis of Growth Kinetics and Clinical Outcomes Stratified by Radiological Characteristics at Diagnosis.  Ryan Dorin, Antonio Cusano*, Max Jackson, Stuart Kesler, Anoop Meraney, Steven Shichman, Hartford, CT


A number of presentations demonstrated improved diagnostic techniques. Differentiating RCC and oncocytoma can be difficult based on enhanced axial imaging.  Simply looking at the presence of hematuria improved the ability to discriminate between the two entities (MP36-14).  In addition, using clinical parameters including tumor size, sex and RENAL nephrometry score could improve the ability to determine benign histology, malignant histology and potentially aggresive tumors (MP40-09).  For instance, women with <3cm tumors and low-complexity tumors had only a 64% chance of malignancy and on 9% had high-grade tumors; while 90% of men with >3cm tumors and nephrometry scores >8 had RCC and 35% had high-grade cancers.  Hear the webcast of this study at UroToday.

MP36-14: Can Hematuria be Used to Predict RCC vs. Oncocytoma Histology? Michael Hanzly*, Terry Creighton, Christine Murekeyisoni,, Elizabeth Devine, Shervin Badkhshan, Michael Mungillo, Thomas Schwaab, Eric Kauffman, Buffalo, NY
MP40-09: Preoperative predictors of malignancy and unfavorable pathology for clinical T1a renal tumors treated with partial nephrectomy.  Mark Ball*, Michael Gorin, Baltimore, MD, Sam Bhayani, St. Louis, MO, Craig Rogers, Detroit, MI, Michael Stifelman, New York, NY, Jihad Kaouk, Homayoun Zargar, Cleveland, OH, Susasn Marshall, New York, NY, Jeffrey Larson, St. Louis, MO, Phillip Pierorazio, Mohamad Allaf, Baltimore, MD


In an impressive, "out-of-the-box" presentation in a basic science section, Drs. Alexander and Dorai from New York Medical College used 5'AMP to induce a gobal hypometabolic state similar to to hibernation and were able to attenuate the effects of renal ischemia in an animal model (MP29-09).  A number of studies looked at surgically-induced chronic kidney disease (CKD-S).  Researchers found that patients who developed CKD-S had worse overall and cancer-specific survival (PD16-02).  The group from Columbia University found that there were no differences in renal functional outcomes or overall survival for patients undergoing PN or RN if they had no CKD or Stage 3 CKD and the only benefits with respect to nephron-sparing surgery was found in patients with intermediate levels of CKD (PD17-10).  Another study found that the benefits of PN were not observed in patients >65 years of age (MP54-20).  The benefits of nephron-sparing surgery with respect to renal function are well understood, however the patients who most benefit from nephron-sparing surgery is still to be defined.  

A number of other studies examined ischemia time and parenchyma saved during PN to predict renal functional outcomes.  Important observations from presentations included: there was no difference between zero ischemia and warm ischemia <30 minutes (MP54-13) and that quantity, not quality of parenchyma saved predicted renal functional outcome (PD17-03).  Finally, an important study using SEER, showed that patients with low-grade or any T1 clear-cell RCC with end-stage renal disease should proceed directly to transplant without a waiting time as there risk of recurrence was negligible and not increased due to immunosuppression (MP59-10).

PD16-02: IMPACT OF RENAL SURGERY ON OVERALL, ONCOLOGIC, AND CARDIAC MORTALITY IN PATIENTS WITH STAGE I RENAL CELL CARCINOMA AND WITHOUT PREOPERATIVE RENAL INSUFFICIENCY.  Jason Woo*, Michael Liss, Nishant Patel, San Diego, CA, Reza Mehrazin, Memphis, TN, Hak Lee, San Diego, CA, Anthony Patterson, Jim Wan, Memphis, TN, Ithaar Derweesh, San Diego, CA
PD17-10: Renal Failure Following Partial vs Radical Stratified by Preoperative CKD Stage.  Solomon Woldu*, Matthew Danzig, Rashed Ghandour, Aaron Weinberg, Natasha Leigh, Ruslan Korets, Ketan Badani, James McKiernan, Guarionex Joel DeCastro, New York, NY
MP54-20: Overall survival and renal function of partial and radical nephrectomy among older patients with localized renal cell carcinoma: multicenter study.  Jae Seung Chung*, Busan, Korea, Republic of, Seok Soo Byun, Sang Eun Lee, Sung Kyu Hong, Sang Chul Lee, Seongnam, Korea, Republic of, Chang Wook Jeong, Hyeon Hoe Kim, Cheol Kwak, Ja Hyeon Ku, Seoul, Korea, Republic of, Yong June Kim, Cheongju, Korea, Republic of, Seok Ho Kang, Sung Hoo Hong, Won Suk Choi, Seoul, Korea, Republic of
MP54-13: The effects of prolonged warm ischemia on late renal function after robotic partial nephrectomy.  Oktay Akca*, Homayoun S. Zargar, Luis Felipe Brandao, Humberto Laydner, Riccardo Autorino, Jayram Krishnan, Dinesh Samarasekera, George P. Haber, Robert J. Stein, Jihad H. Kaouk, Cleveland, OH
MP59-10: Immunosuppression does not worsen disease-specific survival among patients with renal carcinoma who have undergone renal transplantation.  Bhalaajee Meenaski-Sundaram*, Oklahoma City, OK, Oluwakayode Adejoro, Sean Elliot, Minneapolis, MN, Puneet Sindhwani, Joel Slaton, Oklahoma City, OK
PD17-03: POORLY FUNCTIONING KIDNEYS RECOVER FROM ISCHEMIA DURING PARTIAL NEPHRECTOMY AS WELL AS STRONGLY FUNCTIONING KIDNEYS.  Maria Carmen Mir*, Toshio Takagi, Rebecca Campbell, Nidhi Sharma, Erick Remer, Jianbo Li, Sevag Demirjian, Jihad Kaouk, Steve C Campbell, Cleveland, OH


Finally, in the area of advanced disease, the group from MD Anderson demonstrated that lymph node dissection was protective in patients with T4 and metastatic disease (MP36-20).  For patients with renal vein thrombus, BMI<20, preoperative anemia, renal fat invasion, non-clear cell histology and grade 4 disease predicted survival (PD16-04).  Another presentation demonstrated that blood transfusion, in a dose-dependent fashion, was associated with worse survival for patients undergoing surgery for RCC (PD16-03).  Patients with >1cm and multiple lung nodules were more likely to have metastatic RCC (PD17-07).  When considering patients at highest risk for recurrence, those who recurred within 1 year of initial surgery had the highest mortality from RCC with rates of cancer-specific mortality decreasing with later follow-up (MP40-14).

MP36-20: Survival and Prognostic Variables Predicting Survival in T4 Renal Cell Carcinoma.  Dae Y. Kim*, Christopher G. Wood, Angie Busch, Wei Qiao, Pheroze Tamboli, Eric Jonasch, Nizar M. Tannir, Surena F. Matin, Jose A. Karam, Houston, TX
PD16-04: CURATIVE SURGERY IN RCC WITH THROMBUS; A COMPREHENSIVE RISK MODEL FROM A MODERN MULTICENTER ANALYSIS.  Tyler M. Bauman*, Madison, WI, Vitaly Margulis, Dallas, TX, Christopher G. Wood, Houston, TX, William P. Christensen, Madison, WI, Vishnukamal Golla, Houston, TX, Ramy F. Youssef, Laura-Maria Krabbe, Dallas, TX, David F. Jarrard, Tracy M. Downs, E. Jason Abel, Madison, WIPD16-03: The Impact of Perioperative Blood Transfusion on Survival Following Nephrectomy for Non Metastatic Renal Cell Carcinoma.  Brian Linder*, R. Houston Thompson, Bradley Leibovich, John Cheville, Christine Lohse, Dennis Gastineau, Stephen Boorjian, Rochester, MN
PD17-07: The Clinical Significance of Indeterminate Pulmonary Nodules in Renal Cell Carcinoma.  Roy Mano*, Emily Vertosick, Alexander Sankin, Michael Chevinsky, Yaniv Larish, Christopher Jakubowski, Andreas Hoetker, A Ari Hakimi, Daniel Sjoberg, Oguz Akin, Paul Russo, New York, NY
MP40-14: Predictors of cancer-specific survival after disease recurrence in patients with renal cell carcinoma: The effect of time to recurrence.  Malte Rieken*, Luis Kluth, Evanguelos Xylinas, New York, NY, Umberto Capitanio, Alberto Briganti, Milan, Italy, Laura-Maria Krabbe, Vitaly Margulis, Dallas, TX, Jay Raman, Mikhail Regelman, Hershey, PA, Tobias Klatte, Vienna, Austria, Matthew Kent, Daniel Sjoberg, New York, NY, Alexander Bachmann, Basel, Switzerland, Shahrokh Shariat, Vienna, Austria

To read the entire abstract follow the links below:
For podium presentations (PD5-), click here.
For poster presentations (MP10-), click here.

Phillip M. Pierorazio, MD is an Assistant Professor of Urology & Oncology, Director of the DISSRM Registry and Director of the Division of Testicular Cancer at the Brady Urological Institute at Johns Hopkins.  

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