Review Articles

  • Review Article |

    In this Review, the authors discuss the molecular and histopathological evidence supporting pathology-driven therapy for advanced bladder cancer, including rare histological subtypes of urothelial carcinoma and non-urothelial carcinomas, and highlight novel molecular taxonomies, relevant biomarkers and promising future therapies.

    • Constantine Alifrangis
    • , Ursula McGovern
    • , Alex Freeman
    • , Thomas Powles
    •  & Mark Linch
  • Review Article |

    This Review by Ricketts and Linehan comprehensively summarizes the findings of The Cancer Genome Atlas analyses of renal cell carcinoma and their clinical implications. The authors highlight unique and shared features of the tumour histological subtypes, their predictive power and their possible utility as therapeutic targets.

    • W. Marston Linehan
    •  & Christopher J. Ricketts
  • Review Article |

    Physical activity has been shown to help erectile dysfunction (ED); however, the use of physical activity to actually treat ED is limited, and explicit guidelines are required. In this Review, Allen describes mechanisms underlying the effect and suggests an exercise treatment programme for ED.

    • Mark S. Allen
  • Review Article |

    Increasing evidence suggests that patients undergoing trimodality bladder-preserving treatment (TMT) and radical cystectomy have comparable outcomes but many continue to be offered surgery. This Review discusses the development of TMT and highlights how technological and biological advances could inform personalized treatment strategies.

    • Yee Pei Song
    • , Alan McWilliam
    • , Peter J. Hoskin
    •  & Ananya Choudhury
  • Review Article |

    Tissue engineering using different cell types and tissue scaffolds offers a promising alternative to substitution urethroplasty, which can be associated with complications, restenosis and poor quality of life. In this Review, the authors describe advances in tissue engineering for urethral replacement and consider the future of the field.

    • Filippo Pederzoli
    • , Gregory Joice
    • , Andrea Salonia
    • , Trinity J. Bivalacqua
    •  & Nikolai A. Sopko
  • Review Article |

    In this Review, the authors discuss the emerging oncogenic roles of long non-coding RNAs in prostate, kidney and bladder cancers, highlighting unique opportunities to improve diagnosis, treatment and precision medicine strategies in these genitourinary malignancies.

    • Ronan Flippot
    • , Guillaume Beinse
    • , Alice Boilève
    • , Julien Vibert
    •  & Gabriel G. Malouf
  • Review Article |

    In this Review, Amarasekera and colleagues consider the effect of prostate cancer diagnosis and treatment on men in sexual minority groups, including men who have sex with men and transgender women as well as men with HIV, and discuss how and why efforts to study this population are complicated and evolving.

    • Channa Amarasekera
    • , Vincent Wong
    • , Emily Yura
    • , Adarsh Manjunath
    • , Edward Schaeffer
    •  & Shilajit Kundu
  • Review Article |

    Urinalysis has long been used as a tool for managing diseases, but 21st century techniques have enabled measurement of metabolomic urinary cancer biomarkers using NMR and mass spectrometry. In this Review, the authors discuss the current status of research developments and offer recommendations to help systematize future research in the field.

    • Sarah S. Dinges
    • , Annika Hohm
    • , Lindsey A. Vandergrift
    • , Johannes Nowak
    • , Piet Habbel
    • , Igor A. Kaltashov
    •  & Leo L. Cheng
  • Review Article |

    Machine learning (ML) is revolutionizing and reshaping health care, and computer-based systems can be trained to perform complex tasks in bioinformatics, medical imaging and medical robotics. In this Review, Goldenberg et al. consider ML in the management of prostate cancer, with growing applications in diagnostic imaging, surgical interventions, skills training and assessment, digital pathology and genomics.

    • S. Larry Goldenberg
    • , Guy Nir
    •  & Septimiu E. Salcudean
  • Review Article |

    Many of the bacterial components of the female urinary tract have been characterized, but the viral fraction of this community is largely unknown. Here, the authors describe the current knowledge of bacteriophages within the urinary tract and their possible contribution to urinary tract health.

    • Andrea Garretto
    • , Taylor Miller-Ensminger
    • , Alan J. Wolfe
    •  & Catherine Putonti
  • Review Article |

    In this Review, the authors discuss biomarker-driven prostate cancer molecular subtyping and the development of nanodiagnostic strategies to refine biomarker detection. They also describe the challenges of merging both aspects for precision prostate cancer management.

    • Kevin M. Koo
    • , Paul N. Mainwaring
    • , Scott A. Tomlins
    •  & Matt Trau
  • Review Article |

    Ambulatory urodynamic monitoring (AUM) offers numerous advantages over office-based urodynamics for evaluating urological conditions. This Review describes current trends and limitations of traditional urodynamics and advantages of AUM and highlights emerging telemetric AUM devices for bladder pressure and volume monitoring.

    • Benjamin Abelson
    • , Steve Majerus
    • , Daniel Sun
    • , Bradley C. Gill
    • , Eboo Versi
    •  & Margot S. Damaser
  • Review Article |

    The mesenchymal stem cell (MSC) secretome offers numerous advantages over cell-based therapy, with similar therapeutic effects. Here, the authors discuss the preclinical therapeutic promise of the MSC secretome in regenerative urology, highlighting putative mechanisms of action, characterization methods and future perspectives.

    • Daniel Z. Sun
    • , Benjamin Abelson
    • , Paurush Babbar
    •  & Margot S. Damaser
  • Review Article |

    Macrophage migration inhibitory factor (MIF) can promote tumorigenesis by acting directly on cancer cells and by reversing immunosuppression. Advances have been made in our understanding of the role of MIF in the promotion of, and as a treatment target for, genitourinary cancers.

    • Justin C. Penticuff
    • , Benjamin L. Woolbright
    • , Thais M. Sielecki
    • , Scott J. Weir
    •  & John A. Taylor III
  • Review Article |

    In the localized prostate cancer setting, germline BRCA2 mutations confer aggressive clinicopathological features and poor outcomes. This Review discusses the clinical influence of BRCA2 mutations in localized disease, highlighting biological insights into disease aggressiveness from genomic studies and preclinical models.

    • Renea A. Taylor
    • , Michael Fraser
    • , Richard J. Rebello
    • , Paul C. Boutros
    • , Declan G. Murphy
    • , Robert G. Bristow
    •  & Gail P. Risbridger
  • Review Article |

    Investigation of nephrourological diseases is a common indication for CT examination. However, concerns remain regarding the potential risks associated with exposure to ionizing radiation despite a lack of convincing evidence for any such effect at the low doses used for CT scanning. In this Review, experts in the field explain the data in this area and consider how elimination of unnecessary imaging and optimization of medically justified imaging must remain the basis of clinical decision-making.

    • Andrea Ferrero
    • , Naoki Takahashi
    • , Terri J. Vrtiska
    • , Amy E. Krambeck
    • , John C. Lieske
    •  & Cynthia H. McCollough
  • Review Article |

    The re-emerging mosquito-transmitted flavivirus Zika seems to be sexually transmitted and can persist in the male genital tract, presenting as genitourinary symptoms such as haematospermia, prostatitis, painful ejaculation, penile discharge, and oligospermia. In this Review, the authors explain the mechanisms that underlie persistent Zika infections in men and describe why these are crucial to developing guidelines, effective vaccines, and therapies.

    • Fábio A. Kurscheidt
    • , Cristiane S. S. Mesquita
    • , Gabrielle M. Z. F. Damke
    • , Edilson Damke
    • , Analine R. B. de A. Carvalho
    • , Tamy T. Suehiro
    • , Jorge J. V. Teixeira
    • , Vânia R. S. da Silva
    • , Raquel P. Souza
    •  & Marcia E. L. Consolaro
  • Review Article |

    Sexual arousal in women comprises two components: genital arousal and subjective arousal. For some women, genital arousal enhances subjective arousal; for others, the two types of arousal are desynchronous. In this Review, Meston and Stanton describe the mechanisms and the relationship between genital and subjective arousal and consider how they assist in diagnosis and treatment of sexual arousal dysfunction and development of treatments for female sexual arousal dysfunction.

    • Cindy M. Meston
    •  & Amelia M. Stanton
  • Review Article |

    In this Review, the authors describe technologies for image-guided surgery for managing lymphatic metastases in prostate cancer. Refining these technologies should increase precision in the surgical recognition of positive lymph nodes and reduce the morbidity of pelvic lymph node dissection.

    • Fijs W. B. van Leeuwen
    • , Alexander Winter
    • , Henk G. van Der Poel
    • , Matthias Eiber
    • , Nazareno Suardi
    • , Markus Graefen
    • , Friedhelm Wawroschek
    •  & Tobias Maurer
  • Review Article |

    This Review describes the key insights into urologic chronic pelvic pain syndrome (UCPPS) from the first phase of Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network studies and highlights their implications for understanding the pathophysiological basis and clinical management of UCPPS.

    • J. Quentin Clemens
    • , Chris Mullins
    • , A. Lenore Ackerman
    • , Tamara Bavendam
    • , Adrie van Bokhoven
    • , Benjamin M. Ellingson
    • , Steven E. Harte
    • , Jason J. Kutch
    • , H. Henry Lai
    • , Katherine T. Martucci
    • , Robert Moldwin
    • , Bruce D. Naliboff
    • , Michel A. Pontari
    • , Siobhan Sutcliffe
    •  & J. Richard Landis
  • Review Article |

    This Review discusses the challenges in accurately identifying rare prostate circulating tumour cells or bone marrow-derived disseminated tumour cells and the resulting need for prostate-specific, sensitive biomarkers for the detection of these cells in liquid biopsy samples.

    • Emma E. van der Toom
    • , Haley D. Axelrod
    • , Jean J. de la Rosette
    • , Theo M. de Reijke
    • , Kenneth J. Pienta
    •  & Kenneth C. Valkenburg
  • Review Article |

    In this Review, the authors describe the current mechanistic understanding of infection stone formation and growth, including the influence of the organic matrix, microorganisms, and biofilms, highlighting the medical implications of these insights and the importance of multidisciplinary management approaches.

    • Erika J. Espinosa-Ortiz
    • , Brian H. Eisner
    • , Dirk Lange
    •  & Robin Gerlach
  • Review Article |

    Urinary extravasation occurs in ~30% of patients with high-grade renal trauma, but the lack of evidence-based guidelines complicates its clinical management. Here, the authors discuss the diagnosis and management of urinary extravasation, highlighting important knowledge gaps and future research directions.

    • Sorena Keihani
    • , Ross E. Anderson
    • , James M. Hotaling
    •  & Jeremy B. Myers
  • Review Article |

    Nonoperative management is the only treatment option for Peyronie’s disease in the acute phase of the disease, when surgery is contraindicated. In this Review, Tsambarlis and Levine discuss the oral and topical therapies that have been shown to be efficacious and provide recommendations for their use.

    • Peter Tsambarlis
    •  & Laurence A. Levine
  • Review Article |

    The penis is a diverse and rapidly evolving structure, much more complex than its fundamental function — sperm transfer — would seem to require. In this Review, experts in the field discuss the drivers of penis evolution, and consider how the penis might be an ideal characteristic on which to focus in studies to link phenotype with genotype.

    • David J. Hosken
    • , C. Ruth Archer
    • , Clarissa M. House
    •  & Nina Wedell
  • Review Article |

    Transgender persons can be affected by sexual dysfunctions before, during, after, because of, and despite therapy. In this Review, experts in the field discuss trans sexuality across the gender dysphoric spectrum, and suggest ways in which trans persons can be supported in their sexuality and sexual function.

    • Mats Holmberg
    • , Stefan Arver
    •  & Cecilia Dhejne
  • Review Article |

    In this Review, the authors describe the current preclinical research into stem cell therapy for the treatment and prevention of penile fibrotic disorders, including Peyronie’s disease, urethral stricture and corpora cavernosa fibrosis, and highlight their specific mechanisms of antifibrotic activity.

    • Uros Milenkovic
    • , Maarten Albersen
    •  & Fabio Castiglione
  • Review Article |

    In this Review, the authors describe the pathogenesis of uncomplicated urinary tract infections (UTIs). They discuss the need for nonantibiotic treatments and explore the nonantibiotic management options for the prevention and management of recurrent UTI.

    • Néha Sihra
    • , Anna Goodman
    • , Rhana Zakri
    • , Arun Sahai
    •  & Sachin Malde
  • Review Article |

    Patients with stage T1 bladder cancer require meticulous management owing to their high-risk of recurrence, progression and death. Here, Jordan and Meeks describe the natural history, diagnosis, and treatment of T1 bladder cancer, highlighting key challenges and areas of future investigation.

    • Brian Jordan
    •  & Joshua J. Meeks
  • Review Article |

    The low biomass of the urinary microbiota presents methodological challenges for studying their role in urological diseases. Here, the authors describe methods for urinary microbiota profiling, and discuss important technical considerations for sampling, DNA sequencing, data processing and downstream analysis.

    • Lisa Karstens
    • , Mark Asquith
    • , Vincent Caruso
    • , James T. Rosenbaum
    • , Damien A. Fair
    • , Jonathan Braun
    • , W. Thomas Gregory
    • , Rahel Nardos
    •  & Shannon K. McWeeney
  • Review Article |

    Intravesical device-assisted therapies, such as radiofrequency-induced thermochemotherapeutic effect, conductive hyperthermic chemotherapy, and electromotive drug administration, have shown promising efficacy for non-muscle-invasive bladder cancer. Here, Tan and Kelly describe the evidence for these technologies and summarize efficacy, safety, and tolerability outcomes.

    • Wei Shen Tan
    •  & John D. Kelly
  • Review Article |

    Radical cystectomy plus concurrent pelvic lymph node dissection (PLND) provides oncological benefit and useful prognostic information. However, a lack of consensus exists regarding the optimal PLND template. Here, the authors describe and discuss the use of different PLND templates.

    • Marlon Perera
    • , Shannon McGrath
    • , Shomik Sengupta
    • , Jack Crozier
    • , Damien Bolton
    •  & Nathan Lawrentschuk
  • Review Article |

    Renal cell carcinomas (RCCs) harbour mutations in genes encoding chromatin modifiers, which have integral roles in genome maintenance and epigenetic regulation. Here, the authors review the mutational landscape and roles of chromatin modifiers as co-drivers in RCC, highlighting therapeutic opportunities.

    • Aguirre A. de Cubas
    •  & W. Kimryn Rathmell
  • Review Article |

    BCG immunotherapy is the gold-standard treatment for non-muscle-invasive bladder cancer at high risk of recurrence or progression, but many questions remain unanswered regarding its mechanism of action. The authors describe current knowledge of these mechanisms and discuss ways of augmenting BCG immunotherapy.

    • Caroline Pettenati
    •  & Molly A. Ingersoll
  • Review Article |

    Intracytoplasmic sperm injection (ICSI) is the most widely used method of fertilization in assisted reproductive technology. Here, the authors provide a historical overview of ICSI development, discuss indications for ICSI in both male factor and non-male factor infertility conditions, and describe potential consequences of ICSI for the health of resulting offspring.

    • Sandro C. Esteves
    • , Matheus Roque
    • , Giuliano Bedoschi
    • , Thor Haahr
    •  & Peter Humaidan
  • Review Article |

    The holmium:yttrium–aluminium–garnet (YAG) laser has been a standard of care for treating renal stones for the past 20 years. However, it is not without its limitations. In this Review, Fried and Irby discuss new laser technologies that offer an alternative to the holmium:YAG laser and consider fibre-optic approaches for delivery of the laser energy inside the urinary tract.

    • Nathaniel M. Fried
    •  & Pierce B. Irby
  • Review Article |

    Joosten et al. review the main epigenetic alterations involved in renal carcinogenesis and their effects on key signalling pathways. The authors also discuss the utility of epigenetic aberrations as renal cancer biomarkers and their potential as treatment targets.

    • Sophie C. Joosten
    • , Kim M. Smits
    • , Maureen J. Aarts
    • , Veerle Melotte
    • , Alexander Koch
    • , Vivianne C. Tjan-Heijnen
    •  & Manon van Engeland
  • Review Article |

    In this Review, Berish and colleagues outline the development of currently used models of prostate cancer bone metastasis and discuss mechanistic and therapeutic advances made using these models. The authors also suggest future directions to improve the applicability of these models to the metastatic cascade and human disease.

    • Richard B. Berish
    • , Aymon N. Ali
    • , Patrick G. Telmer
    • , John A. Ronald
    •  & Hon S. Leong
  • Review Article |

    Patients with high-risk localized prostate cancer have a poor prognosis, and appropriate treatments are therefore imperative. Herein, the authors present the current clinical evidence of the benefit of neoadjuvant and adjuvant systemic therapies for the treatment of these patients.

    • Géraldine Pignot
    • , Denis Maillet
    • , Emmanuel Gross
    • , Philippe Barthelemy
    • , Jean-Baptiste Beauval
    • , Friederike Constans-Schlurmann
    • , Yohann Loriot
    • , Guillaume Ploussard
    • , Paul Sargos
    • , Marc-Olivier Timsit
    • , Sébastien Vincendeau
    • , Gilles Pasticier
    •  & Delphine Borchiellini
  • Review Article |

    Yang and colleagues discuss the clinical need and rationale for a phosphoproteomics approach to personalizing prostate cancer treatment. They describe current technologies, clinical findings, and challenges and strategies to realizing routine clinical application of phosphoproteomics.

    • Wei Yang
    • , Michael R. Freeman
    •  & Natasha Kyprianou
  • Review Article |

    In this article, the authors discuss cribriform morphology — now recognized as the most aggressive Gleason pattern 4 subtype — and suggest that prostate cancer grading paradigms should be further refined to distinguish cribriform from noncribriform Gleason pattern 4.

    • Matthew Truong
    • , Thomas Frye
    • , Edward Messing
    •  & Hiroshi Miyamoto
  • Review Article |

    The biology of masculinization is important for understanding embryonic developmental processes involved in the development of the male reproductive tract, genitalia and tumorigenesis of prostate cancer. In this Review, the authors describe our current understanding of the regulation of masculinization.

    • Shoko Matsushita
    • , Kentaro Suzuki
    • , Aki Murashima
    • , Daiki Kajioka
    • , Alvin Resultay Acebedo
    • , Shinichi Miyagawa
    • , Ryuma Haraguchi
    • , Yukiko Ogino
    •  & Gen Yamada
  • Review Article |

    The Notch pathway has been shown to act in both an oncogenic and a tumour-suppressive manner depending on its cellular context, and blocking or restoring the Notch pathway could offer a novel therapeutic target in patients with bladder cancer. In this Review, the authors describe what is known about Notch in cancer and discuss the role and potential of this signalling pathway in bladder cancer.

    • Akihiro Goriki
    • , Roland Seiler
    • , Alexander W. Wyatt
    • , Alberto Contreras-Sanz
    • , Akshay Bhat
    • , Akio Matsubara
    • , Tetsutaro Hayashi
    •  & Peter C. Black
  • Review Article |

    Social media offer varied opportunities for education and networking for patients with prostate cancer and health-care professionals, as well as potential uses in research, advocacy, and awareness campaigns. In this Review, leaders in the field discuss social media in prostate cancer and consider the obstacles and potential for their use in the future.

    • Stacy Loeb
    • , Matthew S. Katz
    • , Aisha Langford
    • , Nataliya Byrne
    •  & Shannon Ciprut
  • Review Article |

    Male infertility is a multifactorial pathological condition, and its genetic landscape is highly complex. Here, Krausz and Riera-Escamilla describe our current understanding of the genetics of male infertility and the clinical implications of this knowledge.

    • Csilla Krausz
    •  & Antoni Riera-Escamilla
  • Review Article |

    In this Review, Lotti and Maggi discuss the correlations between sexual dysfunction and male infertility, focusing on the associations between reproductive, sexual, psychological, and general health.

    • Francesco Lotti
    •  & Mario Maggi
  • Review Article |

    Genomic aberrations of the PTEN tumour suppressor are among the most common in prostate cancer. In this Review, the authors describe the roles of PTEN, consider how PTEN status could act as a potential prognostic and predictive biomarker, and discuss the potential of PTEN and its downstream pathways as a therapeutic target.

    • Tamara Jamaspishvili
    • , David M. Berman
    • , Ashley E. Ross
    • , Howard I. Scher
    • , Angelo M. De Marzo
    • , Jeremy A. Squire
    •  & Tamara L. Lotan
  • Review Article |

    Neuroendocrine prostate cancers (NEPCs) are androgen independent and aggressive and have characteristics of epithelial–mesenchymal plasticity and stem-like cell properties. This Review describes the link between lineage plasticity and an emergent NEPC phenotype and how this knowledge can aid in the development of novel therapeutics.

    • Alastair H. Davies
    • , Himisha Beltran
    •  & Amina Zoubeidi
  • Review Article |

    Lee and Gujar review the potential of virotherapy to increase the effectiveness of immunotherapies in prostate cancer. They discuss how oncolytic viruses can improve anticancer immunological responses and strategies for combining virotherapy with other immunotherapies to obtain improved patient outcomes.

    • Patrick Lee
    •  & Shashi Gujar