Reviews & Analysis

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.

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.

Despite the considerable detrimental effects associated with penectomy, squamous cell carcinoma (SCC) of the penis is most commonly treated with surgery. However, SCC at other locations can be successfully managed using chemotherapy and radiation. Here, Jonathan Tward makes a case for organ-sparing treatments for penile cancer, based on data from treatment of SCC at other body sites.

Use of multiparametric MRI for detection of prostate cancer has been increasing and two recent studies have provided high-quality evidence advocating its integration into the diagnostic protocol. A new paradigm for detection of prostate cancer in the era of PROMIS and PRECISION should be adopted globally.

The Guttmacher–Lancet Commission’s report on Sexual and Reproductive Health and Rights for All coincides with raised awareness of this topic as a result of global movements such as #metoo. However, weak political leadership, increasing fragmentation of services, and sustained underfunding pose a threat to sexual and reproductive health globally.

In this Expert Consensus, Grünwald et al. summarize their recommendations for the diagnosis and treatment of patients with renal cell carcinoma and metastasis to the bone. They also outline current challenges and unmet patient needs that should be addressed in the future.

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.

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.

The detection of 78 bacterial species in the urinary tracts of 77 catheterized female patients further emphasizes that the urinary tract is not sterile. However, many questions arise from these findings, not the least of which is what these organisms are doing in the urinary tract.

Metastatic prostate cancer has traditionally been treated with systemic therapy alone, but the issue of oligometastatic disease raises the question of whether local therapy — radical prostatectomy or prostate radiotherapy — should be performed. A number of phase III trials should improve our understanding of metastatic disease and lead to better care of our patients.

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.

Dose-intensified radiotherapy is widely used in prostate cancer treatment but its effect on distant metastasis and overall survival is unclear. A large randomized clinical trial to evaluate the role of external-beam-based dose intensification without androgen deprivation therapy in intermediate-risk disease shows that dose escalation can reduce distant metastases.

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.

Active surveillance protocols rely on the premise that low-risk disease remains indolent. Thus, understanding environmental factors that promote the progression of indolent disease towards aggressive stages is important to manage men on these programmes. In this Perspectives, the authors describe the data regarding the roles of dietary calcium and vitamin D in prostate cancer and consider whether intake should be modified in men with the disease.

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.

The role of 5α-reductase inhibitors (5-ARI) in prostate cancer chemoprevention remains a controversy, as cancer prevention trials with 5-ARIs have shown a decreased incidence of low-grade prostate cancer but a potential increased risk in high-grade disease. Recent studies have shed light on the long-term safety of 5-ARIs in terms of influencing prostate cancer risk.

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.

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.

The FDA recently approved the second-generation antiandrogen apalutamide for the treatment of men with nonmetastatic castration-resistant prostate cancer on the basis of metastasis-free survival data from the SPARTAN trial. However, whether apalutamide is clinically superior to enzalutamide and whether early or late treatment is preferable remains to be defined.

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.