In the Western world, penile cancer is diagnosed in only 1/100 000–1000 000 men, which makes it a rare cancer. The rarity of the disease, especially in countries where routine circumcision has been adopted, makes it a diagnostic and therapeutic conundrum for many urologists, and related oncological specialties alike.
Current management of the disease is nearly exclusively based on small retrospective series, and in all aspects of management of penile cancer, high-quality evidence is lacking. The rare encounter of penile cancer in daily clinical practice combined with limited evidence-based recommendations unfortunately frequently results in suboptimal management. Especially in surgical staging of the groin areas, it has been shown that this procedure is largely underused in the community and understaging and delayed treatment of lymphatic groin metastasis unfortunately directly impact disease-related morbidity and mortality. In countries where centralized healthcare is offered, understaging rates have dropped dramatically resulting in improved survival, and adoption of organ-sparing surgical approaches is higher in centralized healthcare systems. Centralization however, is not evident everywhere and only few countries and governments have widely adopted such an approach. In Europe, the European Commission has taken the initiative to develop reference networks for rare diseases, with penile cancer being a topical focus in eUROGEN, the reference network for rare diseases supported by the European Association of Urology. These networks aim to provide the best care to patients with rare diseases even when reference centers are not in the immediate vicinity.
For localized disease, we have observed over the past 2 decades a paradigm shift toward the universal adoption of organ-sparing surgery as it has become apparent, although based on retrospective analyses and peer reviewed publications, that excessive wide resection margins in penile cancer are often not needed but rather tumor eradication with often only a few millimeters of surgical margins offering excellent oncological outcomes while preserving maximal normal penile tissue whereby minimizing the sexual and psychosocial impact of what has traditionally been a devastating malignancy. Although patients treated with organ-sparing approaches have higher risks of local recurrence, these do not seem to impact cancer-specific survival rates but do preserve the capacity to have sexual intercourse, to void standing upright and when combined with sophisticated reconstructive techniques, the aspect of the penis can be near-normal even after amputation of the glans or distal portion of the penile shaft. Alternatives such as topical therapies, laser surgery, brachytherapy and external beam radiotherapy have all been explored with encouraging results when carefully selected as potential organ-preserving approaches to the local tumor.
In terms of staging, shear wave elastography, fluorodeoxyglucose-PET with MRI and ultrasmall paramagnetic iron oxide enhanced MRI may be paving the way to early uptake of metastatic disease, and the recent development and increased use of video endoscopic inguinal lymphadenectomy and robotic-assisted video endoscopic inguinal lymphadenectomy, have helped to reduce the morbidities of surgical staging while not compromising oncologic outcomes.
For advanced disease, we have very limited evidence-based options and responses to chemotherapy and radiotherapy have for the most part been disapointing, and have been characterized by a high propensity for locoregional recurrence and systemic toxicity. The use of adjuvant chemoradiotherapy following inguinal and pelvic lymph node dissection is under heavy debate although there seems to be a subgroup of patients benefitting from this approach but responders being difficult to identify upfront. A large-scale international randomized controlled trial that should answer this question faces unquestionable challenges due to the rarity of penile cancer. Due to poor responses to classical cytotoxic therapy, there is an urgent need for the development of novel therapies, which could include, but are not limited to, targeted agents and immune checkpoint inhibitors. Increased insights in the genomic alterations underlying penile cancer and the development of cell-lines and animal models may speed up the development of such novel therapies.
In conclusion, there are still many challenges in optimizing the outcomes of this extremely rare cancer. In this dedicated issue of ‘Current Opinion in Urology’, we have invited world experts and thought leaders to discuss these important clinical topics in an effort to provide a comprehensive overview of the current and future standards and exciting opportunities in the diagnosis and management of penile neoplasms. We hope that this issue is helpful in improving your understanding and management of this rare disease, with the ultimate benefit being for patients across the world faced with such debilitating and often life threatening malignancies.
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