William B. Coley: His Hypothesis, His Toxin, and the Birth of Immunotherapy.
This article reviews the origins, development, and future of immunotherapy. PMID: 33008492 [PubMed - as supplied by publisher] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Loughlin KR Tags: Urol Clin North Am Source Type: research

Kidney Cancer: An Overview of Current Therapeutic Approaches.
Abstract The management of metastatic renal cell carcinoma (RCC) has evolved rapidly in recent years with several immunotherapy-based combinations of strategies approved as first-line therapies. Targeted strategies, including systemic antiangiogenesis agents and immune checkpoint blockade, form the basis of a therapeutic approach. With rising rates of recurrence after first-line treatment, it is increasingly important to not only adopt a personalized treatment plan with minimal adverse events but also develop predictive biomarkers for response. This review discusses currently available first-line and second-line t...
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Chowdhury N, Drake CG Tags: Urol Clin North Am Source Type: research

Harnessing Natural Killer Cell Function for Genitourinary Cancers.
This article discusses recent studies showing that urologic tumors are infiltrated by NK cells and that these NK cells are often dysfunctional, but that strategies interfering with inhibitory axes have significant potential to alleviate this dysfunction. PMID: 33008494 [PubMed - as supplied by publisher] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Bhardwaj N, Farkas AM, Gul Z, Sfakianos JP Tags: Urol Clin North Am Source Type: research

Immunotherapy for Localized Prostate Cancer: The Next Frontier?
Abstract Cancer vaccines, cytokines, and checkpoint inhibitors are immunotherapeutic agents that act within the cancer immunity cycle. Prostate cancer has provided unique opportunities for, and challenges to, immunotherapy drug development, including low tumor mutational burdens, limited expression of PD-L1, and minimal T-cell intratumoral infiltrates. Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherape...
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Patel D, McKay R, Parsons JK Tags: Urol Clin North Am Source Type: research

The Potential Role for Immunotherapy in Biochemically Recurrent Prostate Cancer.
Abstract Biochemically recurrent prostate cancer represents a stage of prostate cancer where conventional (continued on next page) computed tomography and technetium Tc 99m bone scan imaging are unable to detect disease after curative intervention despite rising prostate-specific antigen. There is no clear standard of care and no systemic therapy has been shown to improve survival. Immunotherapy-based treatments potentially are attractive options relative to androgen deprivation therapy due to the generally more favorable side-effect profile. Biochemically recurrent prostate cancer patients have a low tumor burden...
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Bilusic M, Einstein DJ, Karzai FH, Dahut WL, Gulley JL, Aragon-Ching JB, Madan RA Tags: Urol Clin North Am Source Type: research

Immunotherapy for Prostate Cancer: Treatments for the "Lethal" Phenotype.
This article presents an update on the evolution of immunotherapeutics that target a more lethal form of prostate cancer and provides the groundwork for future considerations as to how this field should proceed. PMID: 33008497 [PubMed - as supplied by publisher] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Slovin SF Tags: Urol Clin North Am Source Type: research

Application of Single-Cell Sequencing to Immunotherapy.
Abstract Cancer is a highly complex and heterogeneous disease and immunotherapy has shown promise as a therapeutic approach. The increased resolution afforded by single-cell analysis offers the hope of finding and characterizing previously underappreciated populations of cells that could prove useful in understanding cancer progression and treatment. Urologic and prostate cancers are inherently heterogeneous diseases, and the potential for single-cell analysis to help understand and develop immunotherapeutic approaches to treat these diseases is very exciting. In this review, we view cancer immunotherapy through a...
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Beaumont KG, Beaumont MA, Sebra R Tags: Urol Clin North Am Source Type: research

Immunotherapy for Metastatic Prostate Cancer: Current and Emerging Treatment Options.
Abstract The advent of immunotherapy has revolutionized cancer treatment. Prostate cancer has an immunosuppressive microenvironment and a low tumor mutation burden, resulting in low neoantigen expression. The consensus was that immunotherapy would be less effective in prostate cancer. However, recent studies have reported that prostate cancer does have a high number of DNA damage and repair gene defects. Immunotherapies that have been tested in prostate cancer so far have been mainly vaccines and checkpoint inhibitors. A combination of genomically targeted therapies, with approaches to alleviate immune response an...
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Chakravarty D, Huang L, Kahn M, Tewari AK Tags: Urol Clin North Am Source Type: research

Biotech and Breakthroughs in Immuno-Oncology.
This article surveys the clinical development and investment activity with Immuno-Oncology, specifically prostate, kidney, and bladder cancers. PMID: 33008500 [PubMed - as supplied by publisher] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Bockman JM Tags: Urol Clin North Am Source Type: research

Personalized Medicine for the Infertile Male.
Abstract Personalized medicine uses a patient's genotype, environment, and lifestyle choices to create a tailored diagnosis and therapy plan, with the goal of minimizing side effects, avoiding lost time with ineffective treatments, and guiding preventative strategies. Although most precision medicine strategies are still within the laboratory phase of development, this article reviews the promising technologies with the greatest potential to improve the diagnosis and treatment options for male infertility, including sperm cell transplantation, genomic editing, and new biomarker assays, based on the latest proteomi...
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Velez D, Hwang K Tags: Urol Clin North Am Source Type: research

Immunotherapy for Genitourinary Cancers: New Opportunities for Clinical Impact.
PMID: 33008502 [PubMed - as supplied by publisher] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - October 4, 2020 Category: Urology & Nephrology Authors: Nair SS, Tewari AK Tags: Urol Clin North Am Source Type: research

Evolving Role of Urologists in the Management of Advanced Renal Cell Carcinoma.
This article reviews the role of the urologist in medical and surgical therapies, including prognostication, management of locally advanced and metastatic disease, and provides the most recent clinical trial data. PMID: 32600530 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Kapoor A, Kim J, Goucher G, Hoogenes J Tags: Urol Clin North Am Source Type: research

Imaging for Metastatic Renal Cell Carcinoma.
Abstract Patients with renal cell carcinoma may develop metastases after radical nephrectomy, and therefore monitoring with imaging for recurrent or metastatic disease is critical. Imaging varies with specific suspected site of disease. Computed tomography/MRI of the abdomen and pelvis are mainstay modalities. Osseous and central nervous system imaging is reserved for symptomatic patients. Radiologic reporting is evolving to reflect effects of systemic therapy on lesion morphology. Nuclear medicine studies compliment routine imaging as newer agents are evaluated for more accurate tumor staging. Imaging research ai...
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Vig SVL, Zan E, Kang SK Tags: Urol Clin North Am Source Type: research

Epidemiology, Risk Assessment, and Biomarkers for Patients with Advanced Renal Cell Carcinoma.
Abstract In the preceding two decades, several milestones have been reached in the management of patients with metastatic renal cell carcinoma (mRCC), including the development of novel targeted agents paralleling an increased understanding of the molecular biology of this disease process. Recently, a renewed enthusiasm for immunotherapy in the form of immune checkpoint blockade has resulted in significant strides in the treatment of mRCC. Despite these advances, treatment remains challenging for clinicians, and only modest survival benefits are observed with current treatment paradigms. The risk-stratification to...
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Attalla K, Weng S, Voss MH, Hakimi AA Tags: Urol Clin North Am Source Type: research

Sequencing Therapies for Metastatic Renal Cell Carcinoma.
Abstract In an era of several therapeutic options available, optimal treatment sequencing is crucial to providing patients the most effective therapy and promoting quality of life. In clear cell renal cell carcinoma, a combination approach with an immunotherapy backbone, such as nivolumab/ipilimumab or axitinib/pembrolizumab, has a key role in the first-line setting. Safety and activity data support the transition to single-agent targeted therapies in the second-line setting. Nivolumab monotherapy possesses clinical and mechanistic rationale as a second-line therapeutic option for patients treated with targeted th...
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Dizman N, Arslan ZE, Feng M, Pal SK Tags: Urol Clin North Am Source Type: research

Management of Metastatic Renal Cell Carcinoma with Variant Histologies.
Abstract Variant histology renal cell carcinoma (vRCC) encompasses rare non-clear cell subtypes that have long been associated with poor prognosis and minimal response to therapies targeting vascular endothelial growth factor and its receptor. Molecular advances have helped classify vRCC into distinct entities and identify putative targetable driver alterations, such as MET in papillary subtypes. More have since been identified in other vRCC subtypes, including alterations of tumor metabolism, chromatin remodeling genes, cell-cycle genes, and inactivation of tumor suppressors such as TP53 or NF2. New targeted ther...
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Flippot R, Damarla V, McGregor BA Tags: Urol Clin North Am Source Type: research

Neoadjuvant Therapy for Locally Advanced Renal Cell Carcinoma.
Abstract There has been strong interest in using neoadjuvant therapy to decrease recurrence rates and facilitate surgical resection in locally advanced renal cell carcinoma. To date, no evidence exists to support improvement in oncologic outcomes with neoadjuvant therapy. Likewise, although targeted therapies have shown efficacy in tumor downsizing, this does not often translate to downstaging. Use of presurgical therapy for the purpose of downstaging inferior vena cava tumor thrombi is currently not supported. Future studies evaluating the benefit of newer immune checkpoint inhibitors will determine if there is a...
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Westerman ME, Shapiro DD, Wood CG, Karam JA Tags: Urol Clin North Am Source Type: research

Adjuvant Therapy for Localized High-Risk Renal Cell Carcinoma.
This article reviews the use of adjuvant therapies for prevention of recurrence following resection of clinically localized renal cell carcinoma (RCC). Clinical trials evaluating adjuvant therapy for RCC have focused primarily on the use of tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, which had improved outcome in patients with metastatic disease. However, all but 1 trial found no difference in disease-free survival in the adjuvant setting and none improved overall survival. PMID: 32600536 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Wood E, Donin N, Shuch B Tags: Urol Clin North Am Source Type: research

Cytoreductive Nephrectomy in the Era of Tyrosine Kinase and Immuno-Oncology Checkpoint Inhibitors.
This article reviews the literature evaluating the benefit of CN during the evolution of systemic therapy and provides clinical recommendations for current utilization of CN in patients with mRCC. PMID: 32600537 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Biles MJ, Patel HD, Allaf ME Tags: Urol Clin North Am Source Type: research

The Role of Lymphadenectomy in Patients with Advanced Renal Cell Carcinoma.
Abstract The role of lymph node dissection (LND) in the management of renal cell carcinoma (RCC) is controversial. LND serves an indisputable staging role by providing pathologic nodal stage. However, while earlier observational studies had suggested a survival benefit to LND, more recent observational evidence and a randomized trial do not support a survival benefit. The majority of patients with isolated lymph node involvement appear to harbor occult metastatic disease. Still, LND is not associated with increased perioperative morbidity when performed in experienced centers. LND may therefore play a predominantl...
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Unadkat P, Olumi AF, Gershman B Tags: Urol Clin North Am Source Type: research

The Evolving Role of Metastasectomy for Patients with Metastatic Renal Cell Carcinoma.
Abstract Surgical metastasectomy continues to be utilized for patients with solitary or low-volume metastatic renal cell carcinoma (mRCC). Although few high-quality data are available to evaluate outcomes, local treatment is recommended when feasible because it may allow a subset of patients to delay or avoid systemic treatments. With the development of improved mRCC therapies, utilization of metastasectomy has increased because most patients have incomplete responses to systemic treatment of their metastases. This review discusses the rationale and history of metastasectomy, trends in utilization, prognostic fact...
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Dr Hall B, Abel EJ Tags: Urol Clin North Am Source Type: research

Minimally Invasive Surgery for Patients with Locally Advanced and/or Metastatic Renal Cell Carcinoma.
Abstract Despite advances in systemic therapy and immunotherapy, surgery continues to have a role in management of advanced renal cell carcinoma (aRCC). Minimally invasive surgery (MIS) is considered standard of care for smaller, localized tumors due to faster recovery without compromising oncologic outcomes. There are concerns about MIS for aRCC due to a potential risk of inferior oncologic outcomes and unusual patterns of disease recurrence. Recent studies, however, suggest that in properly selected patients with aRCC, MIS can provide improved peri-operative outcomes without compromising oncologic control. ...
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Becher E, Jericevic D, Huang WC Tags: Urol Clin North Am Source Type: research

Radiation Therapy for Patients with Advanced Renal Cell Carcinoma.
Abstract Stereotactic radiosurgery and stereotactic body radiation therapy (SBRT) have led to a resurgence of the use of radiotherapy in the management of advanced renal cell carcinoma (RCC). These techniques provide excellent local control and palliation of metastatic sites of disease with minimal toxicity. Additionally, SBRT to the primary tumor may be efficacious and well tolerated in select patients that are not surgical candidates. Emerging data suggest that SBRT may potentiate the immune response, and current and future study will evaluate if SBRT can improve survival outcomes in patients with metastatic RCC...
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Miccio JA, Oladeru OT, Jun Ma S, Johung KL Tags: Urol Clin North Am Source Type: research

Current Landscape of Advanced and Metastatic Renal Cell Carcinoma Management.
PMID: 32600542 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - July 2, 2020 Category: Urology & Nephrology Authors: Huang WC, Becher E Tags: Urol Clin North Am Source Type: research

Cutting-Edge Evaluation of Male Infertility.
Abstract A male factor is a contributor in 50% of cases of infertility. Although assisted reproductive techniques can often bypass the need to improve semen parameters, the evaluation of the infertile man remains critical. Current methods for evaluating the infertile man are discussed, beginning with the basic workup that all suspected infertile men should undergo, followed by subsequent evaluation steps. Although the fundamental components of the evaluation have remained consistent, several new tools are available to assist in identifying the underlying etiology. As our understanding of male fertility expands, th...
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Pathak UI, Gabrielsen JS, Lipshultz LI Tags: Urol Clin North Am Source Type: research

Optimal Endocrine Evaluation and Treatment of Male Infertility.
This article aims to define the optimal endocrine workup of male factor infertility, including evaluation and treatment of men who have previously been on exogenous testosterone or anabolic steroids. Future directions include the expansion of genetic testing for infertility to include endocrine gene products. PMID: 32272985 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: McGriff SC, Lo EM, Hotaling JM, Pastuszak AW Tags: Urol Clin North Am Source Type: research

Testicular Mapping: A Roadmap to Sperm Retrieval in Nonobstructive Azoospermia?
This article describes various options of sperm retrieval, historic and contemporary, and highlights the advantages and disadvantages of each. The authors find that using a testicular map can invariably help guide sperm retrieval and overall fertility care. The right approach is one that involves a shared decision with the couple. PMID: 32272987 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Kapadia AA, Walsh TJ Tags: Urol Clin North Am Source Type: research

High Sperm DNA Damage: Does Testicular Sperm Make Sense?
Abstract Sperm DNA damage reduces pregnancy rates in couples undergoing in vitro fertilization (IVF). Because it has been shown that testicular sperm have lower DNA damage than ejaculated sperm, it is an attractive idea to consider using testicular sperm for IVF for men with high sperm DNA damage. In fact, there are multiple centers throughout the world now offering sperm retrieval for IVF to manage this condition. However, there is insufficient evidence to conclude that testicular sperm improves pregnancy/live birth rates. Further studies are required before offering sperm retrieval as a standard of care to ...
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Jarvi K Tags: Urol Clin North Am Source Type: research

Round Spermatid Injection.
Abstract From a fertility perspective, men with azoospermia represent a challenging patient population. When no mature spermatozoa are obtained during a testicular sperm extraction, patients are often left with limited options, such as adoption or the use of donor sperm. However, it has been reported that round spermatids can be successfully injected into human oocytes and used as an alternative to mature spermatozoa. This technique is known as round spermatid injection (ROSI). Despite the limitations of ROSI and diminished clinical success rates, the use of round spermatids for fertilization may have potential as...
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Gross KX, Hanson BM, Hotaling JM Tags: Urol Clin North Am Source Type: research

The Role of the Urologist in a Reproductive Endocrinology and Infertility Practice.
Abstract With male factor infertility accounting for up to 50% of infertility cases, demand for male fertility services has increased. Integrating a reproductive urologist within a fertility center allows for treatment of both partners simultaneously with easier, more convenient access to a comprehensive male evaluation and any indicated interventions. A joint practice allows urologists to collaborate more closely with reproductive endocrinologists, which can, in turn, improve clinical care and research endeavors. This full-service, streamlined approach translates to optimized care for the infertile couple and all...
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Cheng PJ, Tanrikut C Tags: Urol Clin North Am Source Type: research

Qualitative Research in Male Infertility.
Abstract Qualitative research methods represent a valuable tool for investigating the entirety of the experience of male infertility evaluation, diagnosis, and treatment. Qualitative research is rigorous and thorough and well adapted for studying the complex field of infertility and reproductive health. Knowledge gained from qualitative research methods can undoubtedly inform clinical practice and improve support for individuals and couples affected by male factor infertility. PMID: 32272992 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Mehta A Tags: Urol Clin North Am Source Type: research

Male Infertility and Somatic Health.
Abstract Somatic health is associated with male infertility; potential links between infertility and health may arise from genetic, developmental, and lifestyle factors. Studies have explored possible connections between male infertility and oncologic, cardiovascular, metabolic, chronic, and autoimmune diseases. Male infertility also may be a predictor of hospitalization and mortality. Additional research is required to elucidate the mechanisms by which male infertility affects overall health. PMID: 32272993 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Murshidi MM, Choy JT, Eisenberg ML Tags: Urol Clin North Am Source Type: research

Transgenerational Epigenetics: A Window into Paternal Health Influences on Offspring.
Abstract Transgenerational epigenetic inheritance provides a mechanism by which environmental exposures and lifestyle decisions can affect the offspring directly through the gamete. It is this pattern of inheritance that has shed light on the fact that preconception lifestyle decisions that a father makes are significant because they can significantly impact the offspring. Understanding the epigenetic alterations in gametes and the potential implications of these changes is key to the health of future generations. PMID: 32272994 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Grover MM, Jenkins TG Tags: Urol Clin North Am Source Type: research

Spermatogonial Stem Cell Culture in Oncofertility.
Abstract Infertility caused by chemotherapy or radiation treatments negatively impacts patient-survivor quality of life. The only fertility preservation option available to prepubertal boys who are not making sperm is cryopreservation of testicular tissues that contain spermatogonial stem cells (SSCs) with potential to produce sperm and/or restore fertility. SSC transplantation to regenerate spermatogenesis in infertile adult survivors of childhood cancers is a mature technology. However, the number of SSCs obtained in a biopsy of a prepubertal testis may be small. Therefore, methods to expand SSC numbers in cultu...
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: David S, Orwig KE Tags: Urol Clin North Am Source Type: research

Personalized Medicine in Infertile Men.
e;s I Abstract Personalized medicine gathers the most relevant data involved in human health. Currently, the diagnosis of male infertility is limited to spermiogram, which does not provide information on the male fertile potential. New diagnostic methods are required. The application of omics techniques in the study of male reproductive health renders a huge amount of data providing numerous novel infertility biomarkers, from genes to metabolites, to diagnose the cause of male infertility. Recent studies hold the promise that these biomarkers will allow a noninvasive infertility diagnosis and the improvement of th...
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Garrido N, Hervás I Tags: Urol Clin North Am Source Type: research

Male Infertility and the Future of In  Vitro Fertilization.
Male Infertility and the Future of In Vitro Fertilization. Urol Clin North Am. 2020 May;47(2):257-270 Authors: Hanson BM, Kaser DJ, Franasiak JM Abstract The male contribution to infertility has traditionally been overlooked, or at best oversimplified. In recent years efforts have been made to optimize diagnostic and therapeutic techniques to maximize fertility outcomes. A renewed focus on the male partner has resulted in an increased understanding of both genetic and epigenetic changes within the male germline. Furthermore, single-nucleotide polymorphisms, copy-number variants, DNA damage, sperm...
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Hanson BM, Kaser DJ, Franasiak JM Tags: Urol Clin North Am Source Type: research

Male Infertility: Is It the Key to the Future of Reproductive Health?
PMID: 32272998 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - April 12, 2020 Category: Urology & Nephrology Authors: Hotaling JM Tags: Urol Clin North Am Source Type: research

Bacillus Calmette-Gu érin Salvage Therapy: Definitions and Context.
This article provides a historical context relevant to the development of the BCG-unresponsive definition, an overview of current clinical trial expectations, and an introduction to this issue of Urologic Clinics. PMID: 31757292 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Konety BR, Narayan VM, Dinney CPN Tags: Urol Clin North Am Source Type: research

Immuno-Oncology Approaches to Salvage Treatment for Non-muscle invasive Bladder Cancer.
This article provides a comprehensive review of the available data for immunotherapy being used as a salvage treatment in non-muscle-invasive bladder cancer. The literature demonstrates that the immune system has an important role in bladder cancer progression. Initial results from studies using checkpoint inhibitors, recombinant interferon-α2b protein, and oncolytic adenoviruses have shown promising responses with acceptable toxicities. However, the majority of the current data arises from small trials with limited follow-up. There are currently several ongoing studies in this setting, which we await completion, to ...
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Sathianathen NJ, Regmi S, Gupta S, Konety BR Tags: Urol Clin North Am Source Type: research

Role of Indoleamine-2,3-Dioxygenase Inhibitors in Salvage Therapy for Non-Muscle Invasive Bladder Cancer.
Abstract Due to significant risks of cancer recurrence and progression, and limited options after intravesical Bacillus Calmette Guerin (BCG) therapy, there is a critical unmet need to identify novel treatments for those patients with BCG-unresponsive bladder cancer. There is active investigation of immunotherapies which provide both biologic and clinical rationales for indoleamine-2,3- dioxygenase inhibitors in salvage therapy for non-muscle invasive bladder cancer. PMID: 31757294 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Chu CE, Porten SP, Grossfeld GD, Meng MV Tags: Urol Clin North Am Source Type: research

Salvage Therapy for Non-muscle-invasive Bladder Cancer: Novel Intravesical Agents.
Abstract Bacillus Calmette-Guerin (BCG)-refractory high-grade non-muscle-invasive bladder cancer remains a challenging problem. Radical cystectomy is standard of care, but carries significant morbidity. Therefore, there is a need for effective treatments. Previous salvage intravesical therapies have had disappointing results with long-term follow-up; however, a wide array of novel agents is currently under investigation. These include novel combinations of existing intravesical agents, novel modes of delivery such as hyperthermia, viral mediated therapies, and immunotherapy. We review the need for novel treatment ...
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Khaled D, Taylor J, Holzbeierlein J Tags: Urol Clin North Am Source Type: research

Identification of Candidates for Salvage Therapy: The Past, Present, and Future of Defining Bacillus Calmette-Gu érin Failure.
This article describes historical definitions of BCG failure, as well as recent efforts to better delineate and refine the clinical criteria for identifying individual patients who will not benefit from further intravesical BCG therapy. It also reviews guidance from the most recent expert consensus panels and professional association guidelines regarding which patients should not receive additional BCG therapy. PMID: 31757296 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Becker REN, Kates MR, Bivalacqua TJ Tags: Urol Clin North Am Source Type: research

Predictors of Response to Intravesical Therapy.
Abstract Despite the 40-year reign of bacillus Calmette-Guérin (BCG) as the most effective immunotherapy in urologic cancers, a lack of clinical tools to predict treatment response has hampered progress in the field. Acting as an immunostimulatory agent against a multitude of phenotypically diverse non-muscle-invasive bladder cancers, response to BCG likely depends on both tumor characteristics as well as host factors. With a deeper understanding of the tumor biology as well as the mechanism of action underpinning immunotherapy, newer and more effective clinical tools are being constructed to improve patien...
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Li R, Kamat AM Tags: Urol Clin North Am Source Type: research

Genomic and Therapeutic Landscape of Non-muscle-invasive Bladder Cancer.
Abstract Non-muscle-invasive bladder cancer (NMIBC) is heterogeneous, but current diagnostic and treatment strategies rely primarily on clinical parameters, lacking individualization to tumor and host genetics and biology. The heterogeneity of NMIBCs is derived from mutations, mutation signatures, chromosomal loss, and disruption of molecular pathways, which ultimately affects tumor progression, recurrence, and responsiveness to intravesical and systemic chemotherapy. Although research is still underway, advances in sequencing technology, insight into differential bacillus Calmette-Guérin responses, and new...
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Cooley LF, McLaughlin KA, Meeks JJ Tags: Urol Clin North Am Source Type: research

Salvage Therapy Using Bacillus Calmette-Gu érin Derivatives or Single Agent Chemotherapy.
Salvage Therapy Using Bacillus Calmette-Guérin Derivatives or Single Agent Chemotherapy. Urol Clin North Am. 2020 Feb;47(1):47-54 Authors: Haas CR, McKiernan JM Abstract Despite therapy with intravesical Bacillus Calmette-Guérin, roughly 50% of patients with high-risk non-muscle-invasive bladder cancer will recur. Although cystectomy is the oncologic gold standard in BCG unresponsive disease, salvage intravesical therapies are valuable treatment options that aim to preserve quality of life while decreasing the risk of cancer recurrence and progression. Single-agent intravesical chemother...
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Haas CR, McKiernan JM Tags: Urol Clin North Am Source Type: research

Salvage Therapies for Non-muscle-invasive Bladder Cancer: Who Will Respond to Bacillus Calmette-Gu érin? Predictors and Nomograms.
Salvage Therapies for Non-muscle-invasive Bladder Cancer: Who Will Respond to Bacillus Calmette-Guérin? Predictors and Nomograms. Urol Clin North Am. 2020 Feb;47(1):5-13 Authors: Faba ÓR, Pisano F, Krajewski W, Breda A, Palou J Abstract The best predictors of response to intravesical immunotherapy are tumor grade and stage, tumor recurrence pattern, nomograms, panels of urinary cytokines, and fluorescent in situ hybridization patterns of urine cytology examinations. Future investigations on predictors of Bacillus Calmette-Guérin efficacy are needed to better select those patients ...
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Faba ÓR, Pisano F, Krajewski W, Breda A, Palou J Tags: Urol Clin North Am Source Type: research

Heated Intravesical Chemotherapy: Biology and Clinical Utility.
Abstract Non-muscle-invasive bladder cancer can be a challenging disease to manage. In recent years, hyperthermia therapy in conjunction with intravesical therapy has been gaining traction as a treatment option for bladder cancer, especially if Bacillus Calmette-Guerin might not be available. Trials of intravesical chemotherapy with heat are few and there has been considerable heterogeneity between studies. However, multiple new trials have accrued and high-quality data are forthcoming. In this review, we discuss the role of combined intravesical hyperthermia and chemotherapy as a novel approach for the treatment ...
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Tan WP, Longo TA, Inman BA Tags: Urol Clin North Am Source Type: research

Apaziquone for Nonmuscle Invasive Bladder Cancer: Where Are We Now?
Abstract Apaziquone is an interesting drug for intravesical use in patients with nonmuscle invasive bladder cancer; however, more research is needed to prove its actual benefit. Although the apaziquone trials demonstrate the potential of this new drug, the singular phase 3 trials did not reach their primary endpoint. To date, no new trials are recruiting, so the development of apaziquone seems to have stopped. PMID: 31757302 [PubMed - in process] (Source: The Urologic Clinics of North America)
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Arends TJH, Alfred Witjes J Tags: Urol Clin North Am Source Type: research

Combination Intravesical Therapy.
Abstract After Bacillus Calmette-Guerin (BCG) failure, there is likely a 6- to 24-month window whereby salvage intravesical therapy might allow for preservation of the bladder without disease worsening. Combination intravesical, salvage therapy for nonmuscle invasive bladder cancer represents a promising avenue for treatment in patients unfit or unwilling to undergo cystectomy. BCG with concomitant immune stimulating agents or immune checkpoint inhibitors, combination chemotherapy regimens, such as gemcitabine and docetaxol, and novel agents currently in clinical trials provide hope for a bladder-sparing alternati...
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Brooks NA, O'Donnell MA Tags: Urol Clin North Am Source Type: research

Intravesical Gene Therapy.
Abstract Non-muscle-invasive bladder cancer is a challenging disease to treat, with few effective salvage intravesical options available for patients who develop bacillus Calmette-Guerin-unresponsive disease. Although radical cystectomy with pelvic lymphadenectomy remains the gold standard treatment for these patients, there remains an unmet need for other options for those who are unable or unwilling to undergo surgery. To this end, intravesical gene therapy is emerging as a potential alternative with promising early data and ongoing efforts to better understand the mechanisms of action to optimize therapy. ...
Source: The Urologic Clinics of North America - November 25, 2019 Category: Urology & Nephrology Authors: Narayan VM, Dinney CPN Tags: Urol Clin North Am Source Type: research