Erdafitinib in BCG-treated high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette-Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment. PATIENTS AND METHODS: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety. RESULTS: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. CONCLUSIONS: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy.

[Value of immunotherapy in the perioperative treatment of localized muscle invasive bladder cancer]. / Stellenwert der Immuntherapie in der perioperativen Behandlung des lokalisierten muskelinvasiven Harnblasenkarzinoms.

Immune checkpoint inhibitors are standard of care in the treatment of metastatic and locally advanced urothelial cancer. Their use in perioperative treatment is currently under investigation as monotherapy as well as in combination with chemotherapy or radiation regimens. This article provides an overview of recent trials, current data as well as an outlook on future developments in the perioperative management of urothelial cancer.

[Quality assurance for the treatment of muscle-invasive and metastasized bladder carcinoma in Germany : An initiative of the Working Groups Urological Oncology (AUO) and Internal Oncology (AIO) in the German Cancer Society (DKG)]. / Qualitätssicherung zur Therapie des muskelinvasiven und metastasierten Harnblasenkarzinoms in Deutschland : Eine Initiative der Arbeitsgemeinschaften Urologische Onkologie (AUO) und Internistische Onkologie (AIO) in der Deutschen Krebsgesellschaft (DKG).

BACKGROUND: The S3-guideline on bladder cancer recommends radical cystectomy and cisplatin-based perioperative chemotherapy (POC) for muscle-invasive bladder cancer (MIBC). Recommendation for metastatic urothelial cancer (mUC) is cisplatin-based or immuno-oncological (IO) treatment in platinum-ineligible patients (pts) or as 2nd-line therapy. OBJECTIVES: Aim of the study was to obtain representative data on clinical routine treatment of MIBC and mUC in Germany. MATERIALS AND METHODS: A nationwide survey was performed to obtain data on stage-related patient volume in hospitals and office-based physicians. Based on these results, a representative sample of treatment data was collected retrospectively from pts with MIBC and mUC. RESULTS: Data from 956 pts (MIBC 576; mUC: 380) were collected. Of the MIBC pts, 49.8% received a systemic therapy (80.4% of them received cisplatin/gemcitabine) and 50.2% were treated with a cystectomy without POC. Significant factors for cystectomy without POC were higher age > 75 years (odds ratio [OR] 4.91, 95% confidence interval [CI] 3.01-8.11, p < 0.001) and platinum-ineligible pts (OR 2.15, 95% CI 1.30-3.59; p = 0.003). Treatment decision without interdisciplinary tumor board was also correlated with no POC (OR 2.43, 95% CI 1.65-3.61, p < 0.001). In mUC platinum-pretreated pts generally receive IO therapy (OR 12.07, 95% CI 6.94-21.82, p < 0.001). Other significant factors are positive PD-L1 status (OR 3.72, 95% CI 1.30-5.71, p < 0.001), higher age > 75 years (OR 2.83, 95% CI 1.43-5.73, p = 0.003) and platinum-ineligible pts (OR 2.57, 95% CI 1.30-5.71, p = 0.007). CONCLUSIONS: The "gold standard" cisplatin/gemcitabine is established in Germany if pts are treated with POC. Nonetheless half of the MIBC pts did not receive a POC, especially if the treatment decision is not discussed in a tumor board. In mUC IO therapy is established as 2nd-line therapy after a platinum-based treatment. Although the guideline recommendations are largely implemented, there is potential for optimization, especially in the establishment of interdisciplinary tumor boards.

Advances in targeted alpha therapy for prostate cancer.

Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment.

[Internet use after prostate cancer : Search for information and trust in disease-related information in long-term survivors]. / Internetnutzung nach Prostatakrebs : Informationssuche und Vertrauen in erkrankungsrelevante Informationen bei Langzeitüberlebenden.

BACKGROUND AND OBJECTIVE: The internet provides numerous sources of information about prostate cancer (PCa). The present study investigated internet use among long-term PCa survivors, trust in online PCa-related information, and associated factors. MATERIALS AND METHODS: Based on the German national research project Familial Prostate Cancer long-term PCa survivors were asked about their internet use in 2017. Associations with sociodemographic (age at survey, children, intimate relationship, education) and disease-related parameters (time since diagnosis, PCa family history, progress) were analyzed using multivariable logistic regression. RESULTS: In all, 4636 long-term PCa survivors were included in the analysis (mean age 76.9 years; standard deviation 6.6 years). Mean follow-up was 14.0 years. Of long-term PCa survivors, 62.1% were using the internet. Among non-users 23.5% expressed strong concerns, among users only 2.8%. Furthermore, 47.2% of internet users sought information about PCa, 18.0% of them indicated difficulties while searching for information. More than half of the users found the online information inappropriate. Lower age, shorter time since diagnosis, progress, and a more frequent internet use were associated with search for information. Only one-third fully trusted online information. Trust in online information was associated with high age, higher educational level, and frequent search for online information. Many survivors stressed that they were primarily trusting their treating urologist. CONCLUSIONS: Two-thirds of long-term PCa survivors are using the internet. A significant proportion expressed difficulties finding proper and reliable information. Urologists should be familiar with online resources on PCa in order to offer advice to patients and to recommend adequate information on the internet.

[Chemotherapy-induced nausea and vomiting : Current recommendations for prophylaxis]. / Chemotherapieinduzierte Nausea und Emesis : Aktuelle Empfehlungen zur Prophylaxe.

The chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent side effects in cytostatic therapy and a profound challenge during the therapy of cancer patients. Therefore, standardized guideline-orientated prophylaxis is essential and a fundamental contribution for the success of treatment. This review summarizes the current recommendations for CINV of the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO), the American Society for Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN) and the S3-guideline Supportive Therapie of the Leitlinienprogramm Onkologie and shall facilitate its use in the daily routine.

[Efficacy of a ketogenic diet in urological cancers patients : A systematic review]. / Wirksamkeit der ketogenen Diät bei urologischen Tumorerkrankungen : Ein systematischer Review.

BACKGROUND: Beside the classical anticancer treatment tumor patients try to find proactive alternative therapies to fight their disease. Lifestyle changes such as introducing a ketogenic diet is one of the most popular among them. The German Association of Urological Oncology (AUO, Arbeitsgemeinschaft Urologische Onkologie) presents a systematic review investigating the evidence of ketogenic diet in cancer patients. MATERIALS AND METHODS: A systematic literature research was conducted in the databases Medline, Livivo, and the Cochrane Library. Only clinical studies of tumor patients receiving chemotherapy while on a ketogenic diet were included. The assessment of the results was performed according to the predefined primary endpoints overall survival and progression-free survival and secondary endpoints quality of life and reduction of adverse effects induced by cytostatics. RESULTS: Nine studies met the inclusion criteria: eight prospective and one retrospective study case series respectively cohort-studies, with a total of 107 patients. Currently there is no evidence of a therapeutic effect of a ketogenic diet in patients with malignant tumors regarding the clinical outcome or quality of life. CONCLUSION: Based on the current data, a ketogenic diet can not be recommended to cancer patients because prospective, randomized trials are missing.

[Metastatic castration-resistant prostate cancer : Use of cabazitaxel taking into consideration current data]. / Metastasiertes kastrationsresistentes Prostatakarzinom : Neues zu Cabazitaxel unter Berücksichtigung der aktuellen Datenlage.

BACKGROUND: At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented. OBJECTIVES: The focus is on the clinical impact of these data. MATERIALS AND METHODS: A group of German experts in the field of urogenital-oncologic expertise discussed the clinical impact with respect to the current data. RESULTS: The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC. CONCLUSIONS: Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20 mg/m2 cabazitaxel.

[PSMA-radioguided surgery in localised recurrent prostate cancer]. / "PSMA-radioguided surgery" beim lokalisierten Prostatakarzinomrezidiv.

Recently, prostate-specific membrane antigen radioguided surgery (PSMA-RGS) was introduced for targeted resection of localised prostate cancer recurrence. Preliminary results show that PSMA-RGS is very sensitive and specific in tracking suspicious lesions intraoperatively. Prerequisite for PSMA-RGS is a positive 68Ga-PSMA positron emission tomography (PET) scan with a preferably singular soft tissue or lymph node recurrence. The first 63 patients treated with PSMA-RGS were analyzed. The extracorporal analysis of a total of 277 tissue specimens yielded the following test quality criteria regarding the presence of malignant tissue: sensitivity 86.2%, specificity 96.4%, positive predictive value 94%, negative predictive value 91.5%. Oncological follow-up data was available from 59 patients. There was a drop in PSA (prostate specific antigen) below 0.2 ng/ml in 38 patients (67%). Of these 38 patients, 17 (45%) are free of biochemical recurrence after a median follow-up of 12.3 months (6.7-31.9 months). Clavien-Dindo grade III complications occurred in 6 of 63 patients (9.5%). In summary, PSMA-RGS proved to be of high value in patients with localised prostate cancer recurrence for exact localisation and resection of oftentimes small metastatic tissue using intraoperative and ex vivo gamma-probe measurements. Furthermore, PSMA-RGS has the potential to positively influence oncological outcomes. However, patient identification on the basis of 68Ga-PSMA PET imaging and clinical parameters is crucial to obtain satisfactory results.

[Sexual medicine in daily practice : Germany-wide questionnaire of urologists]. / Sexualmedizin im ärztlichen Alltag : Bundesweite Umfrage unter Ärzten in der Urologie.

BACKGROUND: Sexual-related problems are very prevalent. Physicians of different disciplines are frequently contacted by men with those problems. OBJECTIVES: The aim of this study was to investigate the situation of sexual medicine in daily practice and to evaluate German urologists' need for further training in this field with a focus on gender-specific differences. MATERIALS AND METHODS: A five-page questionnaire included questions about sexual medicine in daily practice. A focus was set on physicians dealing with sexual medicine in daily practice and their need for further training in this field. In April/Mai 2015, questionnaires were sent per mail to 5955 urologists, urology residents and andrologists throughout Germany. The questionnaire was developed based on previously published studies and a pretest was performed to evaluate comprehensibility. A χ2 test was performed to determine significant gender-specific differences; for this propose response options were dichotomised. P values ≤0.05 were considered significant. RESULTS: The response rate was 16.0%, representing 955 questionnaires. A total of 50 questionnaires from non-urologists were excluded, so 905 questionnaires were analysed. The mean age was 47.7 ± 10.4 years, 78.9% were male, 97.0% had studied in Germany, 86.7% were specialists and 37.7% had further qualification in andrology. CONCLUSION: Our results emphasize the need for further training in sexual medicine, especially for female physicians. This study underlines the demand for advanced qualification in sexual medicine.

Education in sexual medicine - a nationwide study among German urologists/andrologists and urology residents.

Although sexual-related problems are very prevalent, inadequate training for physicians has been reported. The aim was to investigate the educational situation in sexual medicine, including sexual dysfunctions, gender dysphoria and paraphilia, among German physicians in urology and andrology. Additional, barriers when addressing sexual health issues and confidence in taking care of patients with sexual-related problems were evaluated. A questionnaire was sent to 5955 urologists, urology residents and andrologists throughout Germany. The results of this study emphasise the need for continuing education and training in sexual medicine including sexual dysfunctions (83.9%), gender dysphoria (58.2%) and paraphilia (56.6%). Physicians, especially when working in urology, need basic skills in order to feel confident (89.0% in taking care of patients with sexual dysfunctions, 25.8% with gender dysphoria and 22.9% with paraphilia) and be able to reduce several barriers when addressing sexual health issues. The main reported barriers were lack of time (61.0%), inadequate financial compensation (42.5%), lack of necessity (29.9%) and the assumption of patients feeling uncomfortable (20.9%). It is within the competence of urologists and andrologists to correctly assess the situation and to refer patients to multidisciplinary support, such as psychologists, psychosomatics or couple therapists.

[PSMA-radioguided surgery in localized recurrent prostate cancer : Current and future aspects]. / "PSMA-radioguided surgery" beim lokal begrenzten Prostatakarzinomrezidiv : Aktueller Stand und zukünftige Entwicklungen.

Recently, PSMA-radioguided surgery (PSMA-RGS) was introduced for targeted resection of localized prostate cancer recurrence. Prerequisite for preoperative patient selection and localization of tumor recurrence is a positive 68Ga-HBED-CC PSMA positron emission tomography (PET) scan with preferably only singular soft tissue or lymph node recurrence. After injection of In-PSMA I&T or Tc-PSMA-I&S single photon emission computer tomography (SPECT)/computer tomography (CT) examination is performed in every patient to verify radiotracer uptake in tumor lesions. In a preliminary study, 111In-PSMA I&T SPECT/CT could detect about half of the 68Ga-HBED-CC PSMA PET-positive lesions, while nearly all PET-positive lesions could be detected using PSMA-RGS and also five additional lesions compared to 68Ga-HBED-CC-PSMA PET. Follow-up data from 55 patients show a PSA reduction >50% and >90% in 44 (80%) and 29 (53%) patients, respectively. In 34 (62%) patients, a PSA drop to <0.2 ng/ml was observed. In all, 15 (27%) patients received further PC-specific treatment; the remaining 40 (73%) patients did not undergo further treatment. In 33% of patients, surgery-related complications were noted; however, most were regarded as minor. Thus, PSMA-RGS seems to be of high value in patients with localized prostate cancer recurrence with exact localization and resection of metastatic tissue. However, patient selection based on 68Ga-PSMA PET imaging and clinical parameters is crucial to obtain satisfactory oncological results.

[Intravesical radioimmunotherapy of carcinoma in situ of the urinary bladder after BCG failure]. / Intravesikale Radioimmuntherapie des Carcinoma in situ der Harnblase nach BCG-Versagen.

BACKGROUND: In failure to respond to bacillus Calmette-Guérin (BCG) in patients with carcinoma in situ (CIS) of the urinary bladder, radical cystectomy remains the mainstay after BCG failure. OBJECTIVES: The aim of this pilot study was to evaluate tolerability and safety of the α­emitter radioimmunoconjugate instillation in patients after BCG failure. MATERIALS AND METHODS: Nine patients were included. After emptying the bladder via a transurethral catheter, Bi-213-anti-EGFR-mAb was instilled. Treatment was terminated by emptying of the radioimmunoconjugate from the bladder 120 min after instillation. Efficacy was evaluated via endoscopy and histology 6 weeks after instillation. RESULTS: All patients showed excellent toleration of the treatment without any side effects. Treatment resulted in complete eradication of tumor cells in 3 patients and persistent tumor detection in the other 6 patients. CONCLUSIONS: Intravesical instillation of Bi-213-anti-EGFR-mAb is a promising therapeutic option for treatment of in situ bladder cancer after BCG failure for patients who wish to preserve the bladder.

The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma.

Introduction: Immunological pathways are relevant for the effectiveness of conventional cytotoxic chemotherapy. Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma. Objective: To monitor PD-L1 expression on tumor cells and intratumoral infiltration with CD8 positive lymphocytes during perioperative chemotherapy for urothelial cancer and to evaluate their use as potential predictive markers for chemotherapy. Patients and Methods: Sixty-four patients with muscle-invasive urothelial cancer were included in the analysis. Twenty-two patients received preoperative chemotherapy and 42 were treated in an adjuvant setting for locally advanced disease or lymph node metastases. PD-L1 status and the density of infiltration with CD8-positive cells were assessed by immunohistochemistry and analysed for their association with survival (adjuvant group) and response to chemotherapy (preoperative group). For PD-L1 positivity we used a cutoff of 10% positive tumor cells. Results: In the adjuvant group, 11 of 42 patients (26.2%) had PD-L1 positive tumor cells. Twenty-six of 42 (61.9%) patients were highly infiltrated with CD8 + lymphocytes. There was no significant evidence of an association with overall survival for PD-L1 status nor for CD8 infiltration density (p = 0.63 and 0.71). In the preoperative group, eight of the 22 (36.4%) patients were PD-L1 positive and 13 (59%) were highly infiltrated with CD8 + lymphocytes before chemotherapy. There was no evidence of associations with response or survival. Eight patients showed a pathological response to preoperative treatment. These had a significantly longer overall survival than non-responders (p = 0.01). In the preoperative group the pre-treatment expression of the immunologic markers could be compared to the post-treatment status. Only one patient showed a changed PD-L1 status and three patients a changed CD8 status. Conclusions: The tumoral expression of PD-L1 in urothelial carcinoma does not seem to be largely influenced by chemotherapy. Our data do not provide evidence that tumoral expression of PD-L1 and CD8 are useful as prognostic or predictive markers. Small sample size is the major limitation of our study.

[Short version of the German S3 guideline for bladder cancer]. / Kurzform der S3-Leitlinie Harnblasenkarzinom.

Urinary bladder cancer is the second most common cancer of the urogenital system. The Guideline Program in Oncology (Leitlinienprogramm Onkologie) of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF), the German Cancer Society (Deutsche Krebsgesellschaft) and the German Cancer Aid (Deutsche Krebshilfe) as well as 31 different medical societies have developed the first interdisciplinary, evidence-based German guideline for bladder cancer. This short version presents the resulting series of diagnostic and therapeutic recommendations which were based on a systematic literature search and approved by a team of bladder cancer experts. The full version is available under http://leitlinienprogramm-onkologie.de/ .

[Effects of modified inclusion criteria and negative reporting about PSA screening on the number of potentially recruitable patients for the PREFERE study]. / Auswirkungen geänderter Einschlusskriterien und negativer Berichterstattung zum PSA-Screening auf die Zahl potentiell für die PREFERE-Studie rekrutierbarer Patienten.

BACKGROUND: The PREFERE study is currently below expectations. The objective of this study was to investigate the effect of the modification of the inclusion criteria in 2015 on the number of recruitable patients with localized prostate cancer. Furthermore we analyzed whether fewer cases of low-risk prostate cancer were detected in 2014 than in 2010. PATIENTS AND METHODS: Prostate biopsies of 2136 patients (9 hospitals) of the years 2010 and 2014 were retrospectively reviewed, regarding the eligibility for participation in the PREFERE study. RESULTS: According to PREFERE criteria version 3.2, 16.8 % (in 2010) and 16.7 % (in 2014) of the patients fulfilled the inclusion criteria for the study, whereas 41.9 % (in 2010) and 30.1 % (in 2014) of the patients met the criteria in version 5.0. CONCLUSIONS: Our results indicate that the modified inclusion criteria result in an increase in the number of recruitable patients for the PREFERE study. Furthermore, there were 11.8 % fewer cases of potentially recruitable patients in 2014 than in 2010 by use of version 5.0. This is a possible indication for an altered use of prostate biopsy.

[Rectal mucosa metastasis in recurrent prostate cancer : (68)Ga-PSMA-PET/CT allows targeted salvage radiotherapy]. / Rektummukosametastase beim Prostatakarzinomrezidiv : (68)Ga-PSMA-PET/CT ermöglicht eine gezielte Salvagestrahlentherapie.

This article presents for the first time a case of rectal mucosa metastasis of recurrent prostate cancer that was diagnosed with (68)Ga-PSMA PET/CT. After histological confirmation, the patient was treated with salvage radiotherapy. This case report underlines the specificity and efficacy of PSMA-based PET imaging. In case of biochemical relapse, it can be used even at low PSA levels to detect prostate cancer metastases that might also be in atypical locations. Thus, (68)Ga-PSMA PET/CT may allow new options for salvage therapy.