AUA2021 Panel Discussion: The Future of Urologic Oncology: How Will the Role of the Urologic Cancer Surgeon be Affected by Advances in Technology and Science?
By: Samir S. Taneja, MD | Posted on: 03 Sep 2021
Advances in technology and science have greatly influenced the management of urologic cancers over previous decades, and, in doing so, have also evolved the role and approach of the urologist in treatment paradigms. As examples, the clinical implementation of serum prostate specific antigen (PSA) rapidly advanced the role of surgery in early stage prostate cancer, while cross-sectional imaging allowed the identification of early stage renal tumors, opening the door to partial nephrectomy. Scientific advancement and surgical innovation have always gone hand in hand. In the current age of molecular medicine, mechanism-targeting therapeutics, advanced imaging and machine learning, it is unclear how future advances in science and technology will impact the role of the urologic oncologist and surgery in the management of urologic cancers.
The 2021 AUA Annual Meeting plenary session will open on Friday, September 10 with a panel discussion titled The Future of Urologic Oncology: How Will the Role of Urologic Cancer Surgeon be Affected by Advances in Technology and Science?, led by Samir S. Taneja, MD, Professor of Urology and Radiology at the NYU Grossman School of Medicine. A panel of urologic oncologists with particular expertise in evolving technologies and therapeutic approaches will discuss the impact of such scientific advances on urologic oncology practice through targeted talks reviewing the impact of genetics in prostate cancer, immunotherapy in kidney cancer, multimodal therapies in bladder cancer and molecular imaging in urologic malignancy, followed by a panel discussion on the role of surgery in future management paradigms.
Over the last 5 decades, the explosion of modern tools, technologies and methods for genetic sequencing even a few nucleotide base pairs led to important advancements and transition to genomic medicine. Increasing DNA sequencing throughput, along with decreasing cost, has enabled the incorporation of genomic advances into routine clinical care.1 Simpa Salami, MD, MPH, Assistant Professor of Urology at the University of Michigan will discuss the role of prostate cancer genetics/genomics in candidate selection for therapy. Tissue-based prognostic assays, such as Prolaris®, Oncotype DX™ and Decipher®, have already been shown in validation studies to improve the performance of multivariable clinicopathological models for predicting adverse surgical pathology and long-term oncologic outcomes.2–5 Such advances demonstrate the earliest application of genetics in patient selection, with future advances potentially expanding indications for surgery within multimodal approaches. Obstacles to progress do exist, however, in that genetic variation including inter-focal and intra-focal genomic tumor heterogeneity has been reported in several malignancies, including prostate, kidney and lung cancers, and has been shown to affect oncologic outcomes.6–10 For example, in a recent genomic characterization of localized prostate cancer, multiple subclones of cancer were found in the majority of patients.10 Multiclonality among cases of localized disease was associated with a higher risk of relapse, suggesting that biomarkers that can capture tumor heterogeneity are needed to facilitate accurate risk stratification and treatment selection, a known limitation of currently available tissue-based biomarkers.6
Molecular imaging is another area of rapid advances in the characterization of urologic cancers, with most recent innovations falling within the management of prostate cancer. Edouard Trabulsi, MD, Professor of Urology at Jefferson Medical College, will discuss the impact of molecular imaging on urologic oncology. While a number of promising ligands have emerged as tools for improving detection of occult metastasis, the advent of prostate specific membrane antigen (PSMA)-targeting positron emission tomography (PET) ligands has the potential to greatly alter conventional paradigms for approaching high risk and recurrent prostate cancer.11–13 Recent approval of the 18F-DCFPyL-PET ligand by the U.S. Food and Drug Administration (FDA) was based on the outcomes of the CONDOR and OSPREY trials demonstrating the ligand carries strong positive predictive value (PPV) for nodal disease detection, even at relatively low PSA. In the CONDOR study, 18F-DCFPyL-PET computerized tomography (CT) was evaluated in men with recurrence after primary treatment.14 Management was altered by the findings of the study in two-thirds of men, with approximately 85% accurate disease localization at median PSA of 0.8 ng/ml. In the OSPREY study, among men with high risk localized disease, 18F-DCFPyL-PET demonstrated an 86.7% PPV and 83.2% negative predictive value (NPV) for nodal metastasis, greatly improving preoperative assessment of metastatic risk.15 The findings of these studies demonstrate the ability of this new tool to alter treatment selection and surgical planning. Thematically, molecular imaging offers such potential beyond prostate cancer, empowering the efficacy of surgical interventions through better selection of candidates and individualized surgical planning. Prognostically, molecular imaging may provide future insights into early administration of adjuvant or multimodal therapy.
Immunotherapy and biologic approaches to advanced kidney cancer have been a focus of the urologic community for the past 5 decades. Dating back to the early 1980s, there has been a continual interplay between surgery and biologic therapy in the management of disease. While focus on immunotherapy declined with knowledge of the genetic mechanisms underlying renal carcinogenesis and the development of anti-angiogenic agents and tyrosine kinase inhibitors, recent efforts to develop agents targeting the PDL-1 checkpoint have resulted in a renewed interest in immunotherapy. Brian Shuch, MD, Associate Professor of Urology at the UCLA School of Medicine, will discuss advances in biologic therapy for renal cancer and the impact such advances may have on future practice. Combining immunotherapeutic and biologic agents has emerged as a new frontier in therapy,16–19 allowing the urologic community to re-test the efficacy of agents in the neoadjuvant, adjuvant20 and metastatic setting. Underpinning the advances is the swaying pendulum of the role of cytoreductive and consolidative surgery in the management of metastatic disease. More efficacious systemic interventions with new therapeutic targets such as HIF-2a21 potentially further open the door to more effective use of surgery within multimodal approaches.
The development of PDL-1 checkpoint targeting agents has also had great impact on the management of urothelial cancers, with particular influence on defining new paradigms for multimodal treatment.22–25 Cheryl T. Lee, MD, Professor and Chair of Urology at the Ohio State University School of Medicine, will review recent advances in multimodal therapies for bladder cancer. Historically, surgery has remained the mainstay of treatment for high risk and invasive bladder cancers. Cisplatin-based chemotherapies have improved surgical outcomes and potentially expanded the pool of surgical candidates, but the role of surgery in advanced disease has been limited to palliation. Recent studies demonstrating durable efficacy for PDL-1 checkpoint inhibition in patients with advanced bladder cancer offer potential to consider novel paradigms with alternative roles for surgery in consolidation and alternatives to surgery in poor risk candidates through multimodal bladder sparing protocols, and improved efficacy of surgery in those with earlier stage disease through neoadjuvant therapy.26 The recent approval of pembrolizumab in bacillus Calmette-Guérin (BCG)-refractory nonmuscle invasive bladder cancer demonstrates potential to improve on outcomes in all stages of disease.27
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- Klein EA, Cooperberg MR, Magi-Galluzzi C et al: A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol 2014; 66: 550.
- Bishoff JT, Freedland SJ, Gerber L et al: Prognostic utility of the cell cycle progression score generated from biopsy in men treated with prostatectomy. J Urol 2014; 192: 409.
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- Cooperberg MR, Simko JP, Cowan JE et al: Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J Clin Oncol 2013; 31: 1428.
- Salami SS, Hovelson DH, Kaplan JB et al: Transcriptomic heterogeneity in multifocal prostate cancer. JCI Insight 2018; 3: 3.
- Espiritu SMG, Liu LY, Rubanova Y et al: The evolutionary landscape of localized prostate cancers drives clinical aggression. Cell 2018; 173: 1003.e15.
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- Morrissy AS, Cavalli FMG, Remke M et al: Spatial heterogeneity in medulloblastoma. Nat Genet 2017; 49: 780.
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- Hofman MS, Lawrentschuk N, Francis RJ et al; proPSMA Study Group Collaborators: Prostate-Specific Membrane Antigen PET-CT in Patients with High-Risk Prostate Cancer before Curative-Intent Surgery or Radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet 2020; 395: 1208.
- Calais J, Ceci F, Eiber M et al: 18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. Lancet Oncol 2019; 20: 1286.
- Scarsbrook AF, Bottomley D, Teoh EJ et al; FALCON Study Group: Effect of 18F-fluciclovine positron emission tomography on the management of patients with recurrence of prostate cancer: results from the FALCON trial. Int J Radiat Oncol Biol Phys 2020; 107: 316.
- Morris MJ, Rowe SP, Gorin MA et al; CONDOR Study Group: Diagnostic performance of 18 F-DCFPyL-PET/CT in men with biochemically recurrent prostate cancer: results from the CONDOR phase III, multicenter study. Clin Cancer Res 2021; 27: 3674.
- Pienta KJ, Gorin MA, Rowe SP et al: A phase 2/3 prospective multicenter study of the diagnostic accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY). J Urol 2021; 206: 52.
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- Motzer RJ, Tannir NM, McDermott DF et al; CheckMate 214 Investigators: Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 2018; 378: 1277.
- Eggermont AMM, Blank CU, Mandalà M et al; EORTC Melanoma Group: Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 2021; 22: 643.
- Choueiri TK, Bauer TM, Papadopoulos KP et al: Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med 2021; 27: 802.
- Balar AV, Castellano D, O’Donnell PH et al: First-Line Pembrolizumab in Cisplatin-Ineligible Patients with Locally Advanced and Unresectable or Metastatic Urothelial Cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol 2017; 18: 1483.
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- Balar AV, Galsky MD, Rosenberg JE et al; IMvigor210 Study Group: Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 2017; 389: 67.
- Yu EY, Petrylak DP, O’Donnell PH et al: Enfortumab Vedotin after PD-1 or PD-L1 Inhibitors in Cisplatin-Ineligible Patients with Advanced Urothelial Carcinoma (EV-201): a multicentre, single-arm, phase 2 trial. Lancet Oncol 2021; 22: 872.
- Necchi A, Anichini A, Raggi D et al: Pembrolizumab as Neoadjuvant Therapy before Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): an open-label, single-arm, phase II study. J Clin Oncol 2018; 36: 3353.
- Balar AV, Kamat AM, Kulkarni GS et al: Pembrolizumab Monotherapy for the Treatment of High-Risk Non-Muscle-Invasive Bladder Cancer Unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol 2021; 22: 919.