Updates in the use of radiotherapy in the management of primary and locally-advanced penile cancer

Objective:Penile cancer is a rare malignancy in most developed countries,but may represent a significant oncologic challenge in certain African,Asian,and South American regions.Various treatment approaches have been described in penile cancer,including radio-therapy.This review aimed to provide a synopsis of radiotherapy use in penile cancer management and the associated toxicities.In addition,we aimed to discuss palliative radiation for metastases to the penis and provide a brief overview of how tumor biology may assist with treatment decision-making.Methods:Peer-reviewed manuscripts related to the treatment of penile cancer with radio-therapy were evaluated by a PubMed search(1960-2021)in order to assess its role in the definitive and adjuvant settings.Selected manuscripts were also evaluated for descriptions of radiation-related toxicity.Results:Though surgical resection of the primary is an excellent option for tumor control,select patients may be treated with organ-sparing radiotherapy by either external beam radiation or brachytherapy.Data from randomized controlled trials comparing radiotherapy and surgery are lacking,and thus management is frequently determined by institutional practice patterns and available expertise.Similarly,this lack of clinical trial data leads to divergence in opinion regarding lymph node management.This is further complicated in that many cited studies evaluating lymph node radiotherapy used non-modern radiotherapy delivery techniques.Groin toxicity from either surgery or radiotherapy remains a challenging problem and further risk assessment is needed to guide intensification with multi-modal therapy.Intrinsic differences in tumor biology,based on human papillomavirus infection,may help aid future prognostic and predictive models in patient risk stratification or treatment approach.Conclusion:Penile cancer is a rare disease with limited clinical trial data driving the majority of treatment decisions.As a result,the goal of management is to effectively treat the disease while balancing the importance of quality of life through integrated multidisciplinary discussions.More international collaborations and interrogations of penile cancer biology are needed to better understand this disease and improve patient outcomes.

Genitourinary melanoma:An overview for the clinician

Genitourinary (GU) melanoma is a rare presentation of melanoma accounting for approximately 0.5% of all melanomas.GU melanomas include primary melanomas of the vulva,vagina,uterine cervix,ovary,penis,scrotum,urethra,bladder,ureter,and kidney.These melanomas are often diagnosed in advanced stages and stigma is thought to contribute to delays in presentation.As the likely diagnosing provider,it is imperative that dermatologists,urologists,and gynecologists are aware of these uncommon sites of presentation.While there have been major advances in the treatment of melanomas as a whole in the last 10 years,their applications to GU melanomas have often been overlooked.GU melanomas have not been included in many of the major phase II clinical trials which brought contemporary advanced treatments to market and the prognoses for GU melanomas remain poor.Due to the rarity of GU melanomas,much of the literature provides gener alized recommendations across multiple different organs affected by GU melanomas or omits certain topics,making it difficult to appreciate the funda-mentals of the individual presentations.This review aimed to provide background information on the pathogenesis and epidemiology of the different sites of GU melanomas and categorize data specific to the presentation,staging,treatment,and prognosis of each type of GU melanoma to guide the clinician.It was also meant to encourage a multidisciplinary approach to the management of these patients as it spans the expertise of surgical oncologists,medical oncologists,radiation oncologist,dermatologists,urologists,and gynecologists.

Advancing the field of rare genitourinary tumors:Challenges and opportunities

Firstly,I would like to congratulate the editorial team of the Asion Journol of Urology for dedicating a speclial isue of the joumal to this important toplc.With recent advances in our fundamental understanding of the pathophysiology for many of these tumors in addition to access to high throughput comprehensive genamic profiling.

Revisiting mechanisms of resistance to immunotherapies in metastatic clear-cell renal-cell carcinoma

Renal-cell carcinoma(RCC)remains a leading cause of cancer-related mortality worldwide.Though newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes,resistance to these therapies is becoming a challenge for long-term control.Mechanisms of resistance have been explored in a variety of solid tumors,including RCC.Based upon our review of the current literature on the mechanisms of resistance to immunotherapies for the management of metastatic clear-cell renal cell carcinomas(mccRCC),the ensuing conclusions have been made:The management of mccRCC has progressed substantially with the advent of checkpoint inhibitors and targeted oral therapies,alone and/or in combination.Nevertheless,innate or developed resistance to these therapies remains an ongoing challenge,particularly to immune checkpoint inhibitors(ICIs).Several of the known mechanisms of resistance have been well defined,but recent progression in cellular therapies helps to expand the armamentarium of potential combination options that may overcome these modes of resistance and improve long-term disease control and survival for an otherwise dismal disease.In the ensuing review and update of the literature on the mechanisms of resistance to immunotherapies in mccRCC,we have revisited the known resistance mechanisms of immunotherapies in metastatic clear-cell RCC and explored ongoing and future strategies to overcome them.