Soc. Int. Urol. J., Volume 3, Issue 6 (November 2022) – 13 articles , Pages 363-502

Standard approved systemic treatment options for the management of renal cancer have entirely transformed in the last 15 years and now comprise molecularly targeted therapies against the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR) as well as immune checkpoint inhibitors. These agents may be used alone as monotherapies but increasingly are used in various combinations. The associated important improvements in cancer control and survival have therefore been accompanied by a range of new toxicities. Good management of these toxicities is important for patient safety and quality of life, and also to optimize patients’ opportunity to continue with and therefore benefit from these therapies. The most common toxicities associated with VEGFR tyrosine kinase inhibitors are fatigue, skin rashes, gastrointestinal, stomatitis, hypertension and other cardiovascular toxicities, and hematological and endocrine dysfunction. Common side effects of mTOR inhibitors include asthenia, stomatitis, skin rashes, pneumonitis, metabolic changes and infections. Checkpoint inhibitors can lead to toxicities of any organ system with those seen most frequently including dermatologic, gastrointestinal and hepatic, endocrine, musculoskeletal, and pulmonary, whilst renal, hematological, ophthalmic, cardiac and neurological toxicities are seen less often. In general terms, toxicity management should start preemptively with patient education and may also include a combination of supportive approaches, dose reduction, schedule alteration, treatment interruption and occasionally treatment cessation. Treatment of individual toxicities is dependent on the likely causative agent and is guided by its grade or severity. Specific recommendations for management are discussed in this chapter. Full article

As the therapeutic landscape for metastatic clear cell renal cell carcinoma (mccRCC) expands to include vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and immunotherapies, new challenges are in place for evaluating and treating refractory disease. Assessing and managing refractory disease has several elements: (1) the mechanism(s) of front-line treatment, (2) timing of progressive disease, (3) rapidity and sites of progressing disease, (4) use of adjuvant therapy, and (5) incorporation of surgical and radiation techniques. These variables all have distinct impact on the biology of refractory or resistant mccRCC. A better understanding of the essential mechanisms of both primary and secondary immunotherapy resistance will inform biomarker development and therapeutic strategies in the refractory setting. This paper addresses the current understanding of treatment sequencing in refractory mccRCC, focusing on treatment options with prospective clinical trial data, considers refractory mccRCC after adjuvant immunotherapy, and incorporates radiation or surgical resection for oligoprogressive disease. Full article

Patients undergoing definitive surgery or ablative techniques for nonmetastatic kidney cancer have varying degrees of risk of recurrent disease post procedure. The ultimate goal of “adjuvant therapy” is to reduce the incidence of recurrent disease, and to cure more patients. We summarize the current state of perioperative therapy for kidney cancer and explore future directions to develop optimal adjuvant strategies. We define risk and risk of recurrence post-definitive therapy, describe the controversies surrounding the trial landscape of adjuvant vascular endothelial growth factor receptor tyrosine kinase inhibitors and immune checkpoint inhibitors. We review data on neoadjuvant therapy before advanced kidney cancer resection. Radiologic, ethnic, economic, and geographic considerations with respect to adjuvant therapy are highlighted, as well as adjuvant therapy issues especially pertinent to patients, future directions in adjuvant trial design specifically targeted to biomarkers and patient selection, and sequencing of treatment after adjuvant therapy in those patients with recurrence. Full article

Renal cell carcinoma (RCC) has a natural tendency to invade the venous system with formation of a venous tumor thrombus in the renal vein, which can extend proximally into the inferior vena cava (IVC) and in some cases into the right atrium. The presence of venous involvement significantly worsens prognosis. Despite recent advances in systemic therapies, surgery remains the most effective method of treatment and in the case of complete removal of all tumor, it provides satisfactory long-term survival and must be attempted whenever possible. Several surgical techniques have been proposed, but all are associated with a high rate of perioperative complications and mortality. Minimally invasive approaches are mainly applicable for less extended IVC thrombi, while open surgery remains the gold standard for this category of patients. Most IVC thrombi can be managed without use of circulatory support by using different methods of IVC control depending on the thrombus level. However, use of cardiac bypass with or without deep hypothermic cardiac arrest is indicated in some patients with bulky intraatrial tumor thombi. In select patients presenting with IVC tumor thrombus and synchronous distant metastases, cytoreductive nephrectomy with IVC tumor thrombectomy may be considered with or without neoadjuvant systemic therapy. Surgery for RCC with venous thrombus is complex and requires experienced multidisciplinary surgical, anesthesia, and critical care teams at high-volume centers to achieve the best outcomes. Full article

Surgery with either partial or radical nephrectomy remains the standard of care for localized primary renal cell carcinoma (RCC). However, most RCCs are detected in an older age group, and some may have multiple comorbidities that preclude surgery. Thermal ablation (TA) with radiofrequency ablation (RFA), cryoablation (CA), or microwave ablation (MWA) is considered an alternative to extirpative surgical procedures for select patients with small renal tumors. There is more than 90% post-ablation local control in carefully selected patients with reported complication rates of less than 10%. Most thermal ablation require only a single procedure. More recently, stereotactic ablative body radiotherapy (SABR) has emerged as an attractive noninvasive treatment modality for elderly patients with comorbidities and localized RCC. It has shown more than 90% local control rates for both small and relatively larger tumors (> 4 cm). Modest post-SABR renal function decline has been observed. Despite most patients presenting with mild or moderate chronic kidney disease there is less than a 5% chance of progression to end-stage renal disease. This article aims to summarize the key evidence and ablative treatment’s optimal patient selection, efficacy, and toxicity. Full article

With greater awareness of indolence underlying small renal masses (SRM ≤ 4 cm) and the morbidity of invasive treatment, active surveillance for SRM patients is being increasingly utilized on an international level. This synopsis summarizes the 2022 review and expert opinion recommendations provided to the International Consultation of Urological Diseases (ICUD) by 10 urologists from high-volume active surveillance practices at international centers. Topics reviewed include SRM biology and clinical behavior, current national and international guidelines for active surveillance of SRM patients, active surveillance utilization patterns and barriers to implementation, outcomes and limitations of the active surveillance literature, criteria for active surveillance patient selection, protocols for active surveillance management including frequency/modality of imaging and the role of renal tumor biopsy, triggers for delayed intervention during active surveillance including tumor factors and patient factors, and pathological outcomes of delayed intervention. We conclude that despite limitations of the current literature, active surveillance is a safe initial management strategy for many SRM patients. The slow growth and low metastatic potential of SRMs, combined with no evidence to suggest oncologic compromise with delay to treatment, should provide confidence to both patients and providers who are considering active surveillance. Future research for prioritization should include characterization of long-term active surveillance outcomes including rates of metastasis and delayed intervention, standardization of objective tumor progression criteria for triggering delayed intervention, and further delineation of the role for active surveillance in young and healthy patients. Full article

Imaging plays a central role in the contemporary multidisciplinary management of renal cell carcinoma. This article provides an overview of the current imaging modalities, including ultrasound, computed tomography, multiparametric magnetic resonance imaging, and molecular imaging, used in the evaluation of renal cell carcinoma. A summary of the imaging strategies for renal cell carcinoma staging and restaging post-treatment is provided. Full article

A number of germline syndromes that predispose affected individuals to develop renal cancer have been described, each with unique manifestations, histopathology, and tumor behavior. Patients tend to present with early onset and/or multifocal tumors. Familiarity with these syndromes helps to identify at-risk patients and recommend genetic screening. Early detection is essential to direct appropriate cancer surveillance protocols for patients and other family members and care strategies that preserve lifelong renal function while minimizing risk of death from metastatic cancer. Full article

Renal cell carcinoma is a diverse group of diseases that can be distinguished by distinct histopathologic and genomic features. In this comprehensive review, we highlight recent advancements in our understanding of the genetic and microenvironmental hallmarks of kidney cancer. We begin with clear cell renal cell carcinoma (ccRCC), the most common subtype of this disease. We review the chromosomal and genetic alterations that drive initiation and progression of ccRCC, which has recently been shown to follow multiple highly conserved evolutionary trajectories that in turn impact disease progression and prognosis. We also review the diverse genetic events that define the many recently recognized rare subtypes within non-clear cell RCC. Finally, we discuss our evolving understanding of the ccRCC microenvironment, which has been revolutionized by recent bulk and single-cell transcriptomic analyses, suggesting potential biomarkers for guiding systemic therapy in the management of advanced ccRCC. Full article

The incidence of renal cell carcinoma (RCC) has risen worldwide over the past few decades, and this has been associated with a stage shift. Survival outcomes of RCC depend largely on the stage at diagnosis. Although overall mortality has stabilized or declined in most countries, survival remains poor in late-stage disease, suggesting early detection may improve overall survival outcomes. A number of potential candidate screening tools have been considered (including urinary dipstick, blood- and urine-based biomarkers, ultrasound, and computed tomography [CT]), though it may be that a combination of these approaches may be optimal. Ultimately, the sensitivity and specificity of the chosen screening tool will determine the rate of false positives and false negatives, which must be minimized. One of the key challenges is the relatively low prevalence of the disease, which might be overcome by performing risk-stratified screening or screening for more than one condition (such as combined lung and kidney cancer screening). Both approaches have been shown to be acceptable to the general public, and they may maximize the efficiency of screening while reducing harms. Indeed, quantifying benefits and harms of screening is key (including the impact on overdiagnosis and quality of life). Whether screening for RCC will lead to a stage shift and the impact on survival are the decisive missing pieces of information that will determine whether the screening program might be adopted into clinical practice (along with feasibility, acceptability, and cost-effectiveness). Full article