[New S3 guideline prostate cancer 2021 (version 6.2)-What has changed in advanced prostate cancer?] / Neue S3-Leitlinie Prostatakarzinom 2021 (Version 6.2) ­ Was hat sich beim fortgeschrittenen Prostatakarzinom geändert?

There have been numerous new findings from clinical trials in recent years regarding the treatment of metastatic hormone-sensitive or castration-resistant prostate cancer. The newly approved treatment options make therapy planning and therapy sequencing more challenging. In addition, local therapy of metastatic prostate cancer is becoming increasingly important. In the new German guidelines on prostate cancer (version 6.2, October 2021), new developments in the recommendations for the treatment of mHSPC and mCRPC were implemented, and their most important resulting recommendations for the clinical practice are presented in this review.

[177Lu-PSMA therapy : Current evidence for use in the treatment of patients with metastatic prostate cancer]. / 177Lu-PSMA-Therapie : Aktuelle Evidenzlage beim Einsatz in der Behandlung von Patienten mit metastasiertem Prostatakarzinom.

BACKGROUND: Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and 223Ra), most of these patients still succumb to prostate cancer. Recently, 177lutetium prostate-specific membrane antigen radioligand therapy (177Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy. OBJECTIVES: Establishment of the current position of 177Lu-PSMA-RLT in mCRPC in 2017. MATERIALS AND METHODS: Presentation of the therapy landscape in mCRPC and the current challenges within treatment and survey of the available data on 177Lu-PSMA-RLT after PubMed-based research. RESULTS: In several larger retrospective studies, 177Lu-PSMA-RLT seems to be an encouraging new option with the potential to extend overall survival while displaying a favorable toxicity profile. CONCLUSIONS: Prospective trials are urgently needed to confirm these encouraging results found in retrospective analyses with 177Lu-PSMA-RLT in the treatment of mCRPC.

[Metastatic prostate cancer : Update: position paper for the use of chemotherapy]. / Metastasiertes Prostatakarzinom : Update: Positionspapier zum Einsatz der Chemotherapie.

BACKGROUND: Taxen-based chemotherapy has been established as an effective treatment option in castration-resistant metastatic prostate cancer (mCRPC). Randomized phase III studies, however, have shown that even in the hormone-naïve metastatic state, the early use of chemotherapy in addition to the classical androgen deprivation therapy (ADT) approach leads to a significant increase in median overall survival. OBJECTIVE: This position paper aims to provide current data and orientation in the evidence-based treatment of mPC patients in daily clinical practice. MATERIALS AND METHODS: A German group of clinical experts analyzed the current data and developed criteria for the treatment of mPC patients in daily clinical practice. RESULTS: In the current treatment of hormone-naïve mPC, a beneficial effect of chemotherapy in addition to ADT has become evident. Provided patients are in an appropriate condition, those with a high metastatic load should receive chemotherapy in addition to ADT. Especially in high-risk mCRPC patients (PSA >114 ng/ml, visceral metastasis, ADT response <12 months, tumor-associated complaints), first-line chemotherapy is indicated. After docetaxel failure, continuous treatment with cabazitaxel shows superior overall survival compared to sustained antihormonal therapy. CONCLUSION: Chemotherapy is firmly established in treating patients with mCRPC. Long-term, it will be important to identify molecular predictors. The authors suggest the early use of chemotherapy in hormone-naïve mPC, but note that the approval in this indication is currently nonexistent. After disease progression, patients should be treated analogous to mCRPC.

[Use of the S3 guidelines for early detection of prostate cancer in urological practices]. / Anwendung der S3-Leitlinie zur Prostatakrebsfrüherkennung in urologischen Praxen.

OBJECTIVES: The German S3 guideline on prostate cancer gives recommendations on early detection of prostate cancer. In this study we analyzed the adherence of urologists in private practice from the administrative district of Münster, Germany to this guideline. METHODS: Data were collected through a semistructured survey of 22 urologists based on the COREQ checklist (Consolidated criteria for reporting qualitative research) in four focus groups consisting of five or six urologists in private practice. We developed 23 questions relating to 12 recommendations of the paragraphs of the S3 guidelines dealing with early detection of prostate cancer and prostate biopsy. The recommendations of the guideline are subdivided in nine "strong", one "optional recommendation" and two "statements". The adherence to the guideline was investigated by using frequency and qualitative content analysis (Mayring) based on a mixed methods design. RESULTS: The urologists follow six of the nine "strong recommendations" of the guideline and deviate from three. Reasons for deviations from "strong recommendations" are the following: information about advantages and disadvantages of early detection for prostate cancer, recommendation of a prostate biopsy in case of PSA level ≥4 ng/ml, and indication for repeat biopsy. CONCLUSION: Most of the "strong recommendations" are followed by the interviewed urologists of the administrative district of Münster. Contextually relevant deviations from "strong recommendations" are justified, e. g., the only limited transferability of the PSA threshold of 4 ng/ml derived from population-based studies of asymptomatic men to men presenting in a urologist's office.

Intratumoral expression of programmed death ligand 1 (PD-L1) in patients with clear cell renal cell carcinoma (ccRCC).

The immunological checkpoints of programmed death 1 and its ligand (PD-L1) are currently in focus as novel therapeutic targets in renal cell carcinoma (RCC). The aim of this study was to evaluate the prognostic association of PD-L1 expression in clear cell (cc) RCC with clinical parameters, tumor aggressiveness and overall survival (OS). Patients who underwent renal surgery due to RCC between 1994 and 2003 were retrospectively evaluated. Tumor specimens were analyzed for PD-L1 expression by immunohistochemistry. One hundred and seventy-seven ccRCC patients were eligible for analysis, in which 140 (79.1 %) were negative and 37 (20.9 %) were positive for PD-L1 expression. PD-L1 positivity was associated with female gender (p = 0.001), lymph node metastasis (p = 0.004), distant metastasis (p = 0.002), higher AJCC stage (p = 0.004), as well as advanced disease (pT3/4 and/or N+ and/or M1) (p < 0.001). Kaplan-Meier analysis revealed a significantly diminished 5- and 10-year overall survival of 46.7 and 28.3 % for PD-L1(+) compared to PD-L1(-) tumors with 66 and 53.4 % (p = 0.005), respectively. Univariate analysis showed a significant negative association of OS with PD-L1 positivity [p = 0.005; HR: 2 (95 % CI 1.2-3.3)], even though PD-L1 positivity only tends to predict independently the OS using multivariate analyses [p = 0.066; HR: 1.6 (95 % CI 0.98-2.7)]. PD-L1 expression in ccRCC is associated with parameters of aggressiveness, as well as with poor OS, even though PD-L1 status was not identified as a significant independent prognostic parameter. However, further studies in larger cohorts are warranted.

[Adjuvant vs. salvage radiotherapy after radical prostatectomy]. / Adjuvante vs. Salvage-Strahlentherapie nach radikaler Prostatektomie.

BACKGROUND: After radical prostatectomy (RP) the pre-RP PSA value, Gleason Score, pT-stage, state of seminal vesicles and state of surgical margins are key indicators for the risk of biochemical or clinical recurrence. Depending on the tumour stage, 50-70% of the high-risk patients suffer biochemical progression. The treatment options in these circumstances are adjuvant radiotherapy (ART, for an undetectable PSA) or salvage radiotherapy (SRT, for persisting PSA or PSA re-rising above detection limits). Data from ongoing randomised trials that compare ART and SRT directly have not yet been published. METHOD: A search in PubMed for ART and SRT after RP for prostate cancer was undertaken to compare the results of the 2 treatment approaches. RESULTS: 3 randomised phase-III studies have shown a nearly 20% advantage in terms of biochemical progression after ART (60-64 Gy) compared with a wait-and-see strategy. The largest effect was seen in patients with pT3 prostate cancer with positive surgical margins. According to the German S3-guidelines, SRT with at least 66 Gy can be offered to patients with a post-RP persisting PSA or a PSA re-rising above detection limits. 30-70% of these patients re-achieve an undetectable PSA. Thus, there is a second option for curative treatment. Due to the lower total dose, ART seems to be connected with fewer late complications than SRT. SRT, on the other hand, reduces the risk of potential interactions with post-RP complications and of overtreatment. There is a controversial discussion about the inclusion of the pelvic lymph nodes in the treatment volume, the additional application of anti-androgens and the total dose of both ART and SRT. CONCLUSIONS: The comparison of SRT after PSA progression with ART at a PSA below the detection limits cannot yet be judged conclusively. The indication for ART depends on the associated risk factors. However, regarding freedom from biochemical progression, it is backed up by high level evidence. If SRT is applied for biochemical progression, then it should be initiated early, i. e., at the lowest PSA possible.

[National second opinion network for testicular cancer patients - transferring guidelines into practice!]. / Nationales Zweitmeinungsnetzwerk Hodentumoren - ein System zum Evidenztransfer!

The second opinion network for testicular cancer is an internet-based platform addressed to physicians treating testicular cancer patients. They are offered a second opinion before determining further therapy after orchiectomy and completion of staging procedures. The platform has been used in more than 3,000 cases of testicular cancer to date. The rate of discrepancies between first and second opinions is higher than 30%. This suggests a deficit in the implementation of published therapy guidelines. According to our present interim analysis, the second opinion platform helps in avoiding overtreatment of testicular cancer. The high acceptance of the project and the encouraging results of this interim analysis open the door for expansion of the second opinion model to other diseases, e. g., penile carcinoma.

[Organ-sparing therapy for testicular cancer]. / Organerhaltende Hodentumortherapie.

BACKGROUND: The therapy of malignant testicular neoplasms has always been characterized by a high degree of radicality. Thanks to a number of medical achievements the cure rate of testicular cancer has notably increased through the last decades. In the meanwhile the main focus is on reducing therapy load, scrutinizing radical orchiectomy as the only adequate therapy for the primary tumour. OBJECTIVES: This article discusses the question, if and under which conditions an organ-sparing approach can be used appropriately in clinical practice. MATERIALS AND METHODS: A selective literature search was performed in PubMed. RESULTS: A set of data suggest that endocrine and exocrine function of the testis can be preserved using an organ-sparing approach and many patients could benefit regarding their quality of life, e.g., preserving the ability to father a child at least temporarily and avoiding the need for hormone substitution. Different from kidney tumors, precancerous lesions (testicular intraepithelia neoplasia, TIN) can almost inevitably be found in the surrounding tissue of testicular tumors. This has to be considered when making a decision in favor of an organ-sparing approach, because radiation therapy on the affected testis has to be performed after tumor resection. Despite the absence of prospective data, organ-sparing surgical tumor resection can be recommended in carefully selected patients. CONCLUSION: After careful selection of patients, particularly young men can profit from an organ-sparing therapy regimen. Therefore, organ preservation should always be considered in the surgical treatment of testicular masses.

[Visual diagnosis while performing transurethral resection of bladder tumors: power or myth?]. / Blickdiagnose bei der transurethralen Resektion von Harnblasentumoren : Macht oder Mythos?

INTRODUCTION: The gold standard for diagnosis and immediate therapy of bladder cancer is a transurethral resection (TURB) followed by histopathologic evaluation. The aim of this study was to assess the reliability of visual diagnosis by the operating urologist concerning dignity (malignant/benign) and staging compared to histopathologic evaluation. This is especially crucial since early mitomycin C instillation is based on the urologist's first impression. STUDY DESIGN AND METHODS: This prospective study included 311 cases of TURB from five German institutions. Surgeons were asked to estimate dignity of the neoplasm, tumor stage, and grade according to a standardized questionnaire. RESULTS: The subjective estimation/visual diagnosis of the operating urologist achieved a sensitivity with respect to identifying malignant tumors as such of 97%, while specificity was only 41%. Accordingly, the positive (PPV) and negative predictive values (NPV) were 76% and 88%, respectively. In general, muscle invasive cancer was predicted more often than confirmed by pathology (PPV 52%). However, whenever muscle invasive cancer was excluded by the urologist, this was confirmed by the pathologist in most the cases (NPV 95%). The educational degree did not influence the reliability and predictive value of visual diagnosis. CONCLUSION: This study shows that urologists cannot reliably distinguish benign from malignant lesions of bladder mucosa-regardless of their educational degree. A reliable diagnosis of a pathologist is definitely needed to plan final therapeutic steps.

[Influence of ureter stenting before ureterorenoscopic treatment of ureteral calculi]. / Einfluss der Ureterschienung vor ureterorenoskopischer Behandlung von Harnleitersteinen.

BACKGROUND: Due to a worldwide rise of incidence, urolithiasis presents an increasing strain on the health system. Ureterorenoscopy (URS) is a standard treatment to extract stones in case of ureteral calculi. To increase the success rate of URS and to minimize complications, preoperative ureteral stenting (prestenting) has previously been described as suitable. However, published data are still conflicting. This article describes our single-center experience on the influence of prestenting on the outcome of ureterorenoscopic stone therapy. METHODS: A total of 442 patients who had undergone ureterorenoscopic stone extraction at the Wolfsburg Clinic between 2010 and 2011 were retrospectively evaluated regarding peri- and postoperative results. The Fisher's exact, the χ(2), and the Mann-Whitney U test were used to compare the group of patients with and without prestenting. RESULTS: Even though patients with prestenting suffered from stones with larger diameter that were more frequently located in the proximal ureter, the rates for postoperative stenting, perioperative complications, and retreatment were much lower then in the group of patients without prestenting (p<0.001). Furthermore, patients who had received prestenting had a significantly shorter hospital stay (median, 3 vs. 2 days, p<0.001) and higher rates of stone clearance (83.0 vs. 69.7%, p=0.001). CONCLUSION: According to our retrospective monocentric analysis, prestenting may significantly reduce the risk of complications as well as intra-/post-URS restenting and can increase the rate of complete stone clearance.

[Update Urooncology: News with clinical relevance from major scientific meetings 2013]. / ASCO, ESMO, AUA, EAU, DGU - Update Uroonkologie - Was war klinisch relevant auf den Kongressen 2013?

What is new in urooncology in the year 2013? This review gives a brief but comprehensive overview of new developments in diagnosis and treatment of localized as well as advanced prostate, bladder and kidney cancer which have been presented on the occasion of the annual meetings of the European and American urologic and oncological associations in 2013. Attention is particularly directed to those data and results from trials which might be of direct or indirect clinical relevance.

[Utility of the serum CRP value for assessing the prognosis and therapeutic response of urological malignancies]. / Stellenwert des Serum-CRP-Wertes zur Einschätzung von Prognose und therapeutischem Ansprechen urologischer Malignome.

C-reactive protein (CRP) is an unspecific marker of systemic inflammation. It is known to be elevated in autoimmune disease, traumata and malignancies. Increased CRP levels have specifically been shown to be associated with disease progression and prognosis in various studies on renal cell carcinoma and transitional cell carcinoma. Although CRP, unlike PSA, is neither organ-specific nor tumour-specific, studies were able to show that increased CRP values are an independent prognostic marker for tumour-specific survival of patients with prostate cancer. In metastatic and castration-resistant prostate cancer elevated CRP levels have been approved as a useful marker to estimate the extent of disease and mortality. CRP measurements in serum are standardised worldwide and widely used in daily clinical routine. However, until CRP can be firmly established as a prognostic marker in daily routine, we need validation of its prognostic and predictive value with large and preferably prospective multicentre studies.

Management of muscle-invasive bladder cancer.

The incidence of muscle-invasive bladder cancer (MIBC) is increasing. Many different and multimodal novel treatment options were brought on the way since the beginning of a new era in the early 1980s, when the neobladder as a common option for urinary diversion had been induced. In addition to open radical cystectomy and urinary diversion, recently, minimal invasive surgery has been implemented in experienced centers and led to promising results in short term follow-up, awaiting confirmation in larger cohorts. Pelvic lymphnode dissection can cure patients with low metastatic load. Expansion of pelvic lymphonodal dissection and its influence on survival was discussed intensively with trends to a moderate enlargement of the standard field. Outcome in nodal positive disease is remaining poor, while 90% of patients with multiple lymphnode metastases will suffer from systemic progress 5 years after diagnosis. In the last decade, treatment regimens based on neoajuvant or adjuvant chemotherapy were published with different results on efficiency. To decide whether to treat with surgery alone, or to offer perioperative systemic cytostatic therapy, is one of the unanswered questions. Furthermore, bladder preserving techniques are still optional for patients with small unifocal lesions or the medically unfit cohort. This review summarizes current data and aims to help guiding through several available recommendations on therapy and management of MIBC.

[National second-opinion network for testicular cancer patients. Results of a user survey]. / Nationales Zweitmeinungsnetzwerk testikuläre Keimzelltumoren. Ergebnisse einer Nutzerbefragung.

BACKGROUND: The national second opinion project of the German Testicular Cancer Study Group (GTCSG) has served to improve the quality of care provided to testicular cancer patients since 2006. AIM: A recent online survey was carried out to characterize the users of the second opinion offer and clarify their motivation for participating in the project. Furthermore, the aim was to identify weaknesses of the project which could be improved. A total of 440 users of the second opinion project were contacted of whom 192 participated in the survey. RESULTS: In summary, the data collected showed a high degree of satisfaction among the participants who appreciated the second opinions received. Some issues with a need for improvement, predominantly in the structural organisational area, were disclosed. These served as a basis for a recently completed revision of the project immanent internet-based communication platform with a new data mask facilitating the introduction of patients with relapsed tumors. Interestingly, a high proportion of survey participants expressed the desire for establishment of a similar second opinion project for patients with penile cancer (77.1% of the participants).

[Influence of obesity on urological malignancies]. / Der Einfluss von Adipositas auf urologische Tumorerkrankungen.

BACKGROUND: Overweight presents a growing problem in our society; therefore, there is an increasing interest to understand the influence of obesity on urological forms of cancer. AIM: In prostate cancer the development of a more aggressive phenotype seems to correlate with obesity. In renal cell cancer (RCC) obesity is both, a risk factor for occurrence -and is also associated with an improved tumour-specific survival in patients with organ-confined disease following kidney surgery as well as overall survival of patients with advanced disease receiving VEGF(R)-targeted treatment. In contrast, even though an association between body mass index (BMI) and bladder cancer has been described the role of obesity in bladder cancer remains largely unclear as published data are contradictory. RESULTS: An update on currently available data focusing on the relationship between obesity and genitourinary malignancies is given in this review; however, basic research which is necessary to define the biological and metabolic effects associated with obesity and which might affect the development and progression of urological cancers, is indicated.

[Clinical stage I seminoma. Is surveillance a new therapy standard?]. / Seminom klinisches Stadium I. Neuer Therapiestandard Surveillance?

BACKGROUND: The therapy of stage I seminoma is under constant change. While surveillance, adjuvant radiotherapy and adjuvant chemotherapy were seen as equal therapeutic alternatives up to a few years ago, recently published studies make it necessary to adopt a more differentiated approach. DISCUSSION: In this review, recent data on the long-term effects of adjuvant radiotherapy and chemotherapy, the question of risk stratification as well as the advantages and limitations of a surveillance strategy are discussed.

[The use of Surgisis® optimizes and simplifies partial nephrectomy for large renal tumors]. / Anwendung von Surgisis® zur Optimierung und Vereinfachung der Nierenteilresektion bei größeren renalen Neoplasmen.

BACKGROUND: With lower rates of postoperative renal failure, diabetes and cardiovascular disease, partial nephrectomy achieves longer overall survival and equally long tumor-specific survival. It is thus the current gold standard treatment for renal tumors and now also for those ≥ 4 cm in size. The main complications of nephron-sparing surgery, particularly for large and centrally located tumors, are postoperative parenchymal bleeding and urinary fistulas after opening the urinary collecting system (UCS). MATERIAL AND METHODS: Between August 2003 and April 2012, 76 partial nephrectomies for tumors ≥ 4 cm in size were performed using porcine small intestinal submucosa (SIS, Surgisis®) to close the capsular, renal and in some cases, UCS defects. RESULTS: The median tumor size was 5.0 cm (range 4.0-13.0 cm) and the intervention was performed with warm ischemia in 25 cases (32.8 %), with cold perfusion in 16 cases (21.2 %) and without ischemia in 35 cases (46.0 %). A total of 4 patients (5.5 %) developed postoperative urinary fistulas and 4 (5.5 %) required revision surgery because of significant postoperative bleeding. There were no local infections or allergic reactions to the foreign material. CONCLUSIONS: Surgisis® enables a quick and technically uncomplicated closure of the renal defect after partial nephrectomy for tumors. It has the potential to further minimize postoperative bleeding and urinary fistulas and to facilitate the intervention to the extent that nephron-sparing surgery will gain broader acceptance even in patients with tumors ≥4 cm in size.

[Update urooncology: news with clinical relevance from major scientific meetings 2012]. / Update Uroonkologie: Was war klinisch relevant auf den Kongressen 2012?

What is new in urooncology in the year 2012? This review gives a brief but comprehensive overview of new developments in diagnosis and treatment of localized as well as advanced prostate, bladder and kidney cancer which have been presented on the occasion of the annual meetings of the European and American urologic and oncological associations in 2012. Attention is particularly directed to those data and results of trials which might be of direct or indirect clinical relevance.

[Palliative care and medicamentous therapy during the final episode of life]. / Palliativmedizin und medikamentöse Therapie in der Sterbephase.

The idea of modern palliative care goes back to the times of Dame Cicely Mary Strode Saunders in 1967, a British nurse and physician. Modern palliative care is a multimodal therapeutic and supportive concept for the patient, when curative care has failed or seems to be not reasonable. In this article we review the basics of current palliative care and focus in particular on specific medicamentous therapy during the final episode of life.

[Male sexuality in the elderly]. / Männliche Sexualität im Alter.

Male sexuality in the elderly is an important issue with a growing relevance. In contrast to the assumption of an asexual state when becoming older, recent representative surveys show that the majority of men maintain sexual desires and fantasies into old age. Sexual activity primarily depends on the availability of a partner and on maintaining intimacy and sexuality in the face of changes in the sexual response cycle and increasing comorbidity. This review aims to clarify the normal aging process, the sexual behavior of aging males and the prevalence of sexual dysfunction.