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Squamous cell carcinoma of the penis (SCCP) is a rare cancer type in Western industrialized nations; nevertheless, it shows an aggressive course of disease in advanced tumor stages with accordantly high recurrence and progression rates. While molecular biomarkers are not established in clinical routine for the management of SCCP patients yet, the accordant unmet need is enormous, as adequate biomarkers would be meaningful for prognostic determination, planning of modality and extent of primary therapy, indication for inguinal lymph node resection, adjuvant treatment, and as potential targets for specific systemic treatment. SCCP regularly develops from a precursor lesion. In this regard, human papillomavirus (HPV)-dependent and -independent pathways are differentiated. The potential for specific target therapy options is mainly based on the decoding of genetic and epigenetic signatures of distinct molecular pathways. In order to develop targeted and personalized treatment strategies based on molecular pathways, an increase in translational research in large multi-institutional collaborations must be promoted. This review article aims to summarize the current status of research concerning molecular changes related to SCCP under separate consideration of prognostic molecular markers, on the one hand, and biomarkers considered potential therapeutic targets, on the other hand. In addition, previous research activities of our own working group on this topic are briefly described.

Over the past few decades, some principles in the treatment of penile cancer have changed fundamentally. While 15 years ago a negative surgical margin of at least 2 cm was considered mandatory, organ-sparing surgery permitting minimal negative surgical margins has a high priority nowadays. The current treatment principle requires as much organ preservation as possible and as much radicality as necessary. The implementation of organ-sparing and reconstructive surgical techniques has improved the quality of life of surviving patients. However, oncological and functional outcomes are still unsatisfactory. Alongside with adequate local treatment of the primary tumour, a consistent management of inguinal lymph nodes is of fundamental prognostic significance. In particular, clinically inconspicuous inguinal lymph nodes staged T1b and upwards need a surgical approach. Sentinel node biopsy, minimally-invasive surgical techniques and modified inguinal lymphadenectomy have reduced morbidity compared to conventional inguinal lymph node dissection. Multimodal treatment with surgery and chemotherapy is required in all patients with lymph node-positive disease; neoadjuvant chemotherapy has been established for patients with locally advanced lymph node disease, and adjuvant treatment after radical inguinal lymphadenectomy for lymph node-positive disease. An increasing understanding of the underlying tumour biology, in particular the role of the human papilloma virus (HPV) and epidermal growth factor receptor (EGFR) status, has led to a new pathological classification and may further enhance treatment options. This review summarises current aspects in the therapeutic management of penile cancer.Einige Prinzipien der primären Therapie des Peniskarzinoms haben sich in den letzten Jahrzehnten grundlegend verändert: Galt aufgrund der Aggressivität des Tumors bei der Penisteilamputation vor 15 Jahren noch ein tumorfreier Sicherheitsabstand von 2 cm als obligat, so gilt heute, dass weitgehender Organerhalt Priorität hat und minimale tumorfreie Schnittränder ausreichend sind. Es besteht somit der Grundsatz: So viel Organerhalt wie möglich, so viel Radikalität wie nötig. Auch hat sich zunehmend die Erkenntnis durchgesetzt, dass Patienten mit begrenzter regionär-lymphogener Metastasierung heilbar sein können, allerdings nur bei Durchführung einer multimodalen Therapie bestehend aus einer radikalen inguinalen Lymphadenektomie und nachfolgenden adjuvanten Chemotherapie. Bei Patienten mit fixierten inguinalen Lymphknotenmetastasen konnte hingegen die neoadjuvante Chemotherapie etabliert werden. Trotz der verbesserten Therapieoptionen bleiben die funktionellen und onkologischen Ergebnisse bei der Behandlung des Peniskarzinoms vielfach enttäuschend. Die Möglichkeiten des Organerhalts mittels rekonstruktiver operativer Techniken verbessern zwar die Lebensqualität der Langzeitüberlebenden erheblich, doch weniger als 25 % der Patienten mit Lymphknotenmetastasierung überleben ihre Tumorerkrankung. Von großer Bedeutung ist die chirurgische Lymphknotendiagnostik bei klinisch unauffälligen Lymphknoten ab dem Tumorstadium T1b, da hier eine okkulte Mikrometastasierung in bis zu 25 % der Fälle vorliegen kann. Die minimal-invasive Sentinel-Lymphknoten-Biopsie ist ein durchaus sinnvoller Weg, diese Patienten zu diagnostizieren, ohne gleich die Morbidität einer primär radikalen Lymphadenektomie hervorzurufen. Ein zunehmendes Verständnis der zugrundeliegenden Tumorbiologie, insbesondere Erkenntnisse zum Humanen-Papillomavirus- und Epidermal-Growth-Factor-Receptor-Status, brachten zuletzt erfolgversprechende klinische Studien auf den Weg; zudem wird gegenwärtig die gezielte Immuntherapie mittels Immun-Checkpoint-Inhibitoren bei therapierefraktärem Peniskarzinom geprüft.In diesem Review werden die aktuellen Aspekte des therapeutischen Managements von Peniskarzinom-Patienten zusammengefasst.

Due to increasing antibiotic resistances, relevant treatment problems are currently emerging in clinical practice. In March 2015, the German Federal Ministry of Health (BMG) published a 10-point plan designed to combat this development. Furthermore, the first German guideline on antibiotic stewardship (ABS) was implemented in 2013 and instructs physicians of different specialties about several treatment considerations. Evidence is scarce on how such concepts (10-point plan/BMG, ABS) are perceived among clinicians.Within the MR2 study (Multiinstitutional Reconnaissance of practice with MultiResistant bacteria - a survey focusing on German hospitals), a questionnaire including 4 + 35 items was sent to 18 German hospitals between August and October 2015, surveying internists, gynecologists, general surgeons, and urologists. Using multivariate logistic regression models (MLRM), the impact of medical specialty and further criteria on the endpoints (1) awareness of the 10-point plan/BMG and (2) knowledge of ABS measures were assessed. Fulfillment of endpoints was predefined when average or full knowledge was reported (reference: poor to no knowledge).Overall response rate was 43% (456/1061) for fully evaluable questionnaires. Only 63.0 and 53.6% of urologists and nonurologists (internists, gynecologists, and general surgeons), respectively, attended training courses regarding multidrug-resistance or antibiotic prescribing in the 12 months prior to the study (P = 0.045). The endpoints average and full knowledge regarding 10-point plan/BMG and ABS measures were fulfilled in only 31.4 and 32.8%, respectively. In MLRM, clinicians with at least one previous training course (reference: no training course) were 2.5- and 3.8-fold more likely to meet respective endpoint criteria (all P 0.001). Medical specialty (urologists vs. nonurologists) did not significantly impact the endpoints in both MLRM.The 10-point plan/BMG and ABS programs should be implemented into clinical practice, but awareness and knowledge of both is insufficient. Thus, it stands to reason that the actual realization of such measures is inadequate and continuous training towards rational prescription of antibiotics is necessary, regardless of medical specialty.