[Therapy sequences and duration in mCRPC: a retrospective review of the Lübeck mCRPC cohort]. / Therapiesequenzen und ­dauer beim mCRPC: Eine retrospektive Aufarbeitung der Lübecker mCRPC-Kohorte.

BACKGROUND: Prostate cancer is one of the most common cancers in men in Europe. Several classes of agents can be considered for the treatment of metastatic prostate carcinoma, and their use is supported by extensive guidelines. In the treatment of metastatic castration-resistant prostate cancer (mCRPC), it is currently unclear which sequence of systemic therapies is most effective. Currently approved system therapies in the castration-resistant setting generally include hormone-manipulating agents, taxane-based chemotherapies, radioactive agents, or inhibitiors of DNA repair mechanisms. This study aims to summarize real world data of mCRPC therapy. METHODS: Retrospectively, 90 mCRPC patients undergoing treatment at the University Hospital Schleswig-Holstein, Lübeck Campus between February 2006 and March 2020 were identified. The patient data were analyzed for their treatment sequence and disease progression. Due to the inclusion period, the mCRPC therapy sequences studied were limited to: Abiraterone, Cabazitaxel, Docetaxel, Enzalutamide, Lutetium-177-PSMA and Radium-223. The analysis includes the therapy sequences and their duration, clinical information of the respective cohort, overall and cancer-specific survival (OS/CSS) as well as time to second-line therapy in relation to the respective first-line therapy. RESULTS: Approximately two-thirds of patients underwent a true therapy sequence (at least two of the drugs listed above), with this proportion halving by the third line.The majority of patients received the sequence (first/second line) abiraterone/docetaxel (n=13), followed by docetaxel/abiraterone (n=12) and abiraterone/enzalutamid (n=10) and docetaxel/docetaxel (n=8).Within the different docetaxel sequences, first-line (mean 4.7 months ± SD 3.1; median 4.0) and rechallenge (mean 5.3 months ± SD 5.9; median 3.0) therapy durations were the longest. The subjective side effect rate of docetaxel was lower in the second line, so that a better tolerability can be assumed here.The abiraterone/docetaxel sequence was used mainly in patients with metachronous metastases. Among the different sequences of abiraterone, first-line (mean 10.8 months ± SD 10.2; median 9.0) and second-line (mean 10.6 months ± SD 9.0; median 7.0) therapy durations were the longest.The sequence abiraterone/enzalutamide was prescribed mainly to older patients with synchronous metastases. Among the different enzalutamide sequences first-line (mean 9.6 months ± SD 7.1; median 7.0) and rechallenge (mean 11.0 ± SD 0.0; median 11.0) therapy durations were the longest.In contrast, the sequence docetaxel/docetaxel was used mainly in younger patients with a high initial PSA.The evaluation shows a trend that both abiraterone and enzalutamide can account for a survival advantage in the first line. CONCLUSION: Ultimately, an optimal treatment sequence cannot be confidently derived from these data.However, it was found that only a small proportion of patients underwent fourth- or even fifth-line treatment at all. Thus, the focus on first- and second-line in this study seems reasonable. It could be shown in a trend that docetaxel as first-line therapy seems to be disadvantegous regarding OS as well as CSS when compared to abiraterone or enzalutamide. However, due to the small number of patients in this study, a clear significance cannot be derived. Moreover, the subjectively better tolerability of docetaxel in the second-line setting could provide an impetus for treatment planning in multimorbid elderly patients in the future. The sequence abiraterone/docetaxel may offer a beneficial option for initial mCRPC therapy.

The Role of 12/14F Ureteral Access Sheath in Flexible Ureteroscopy for Moderate Nephrolithiasis.

INTRODUCTION: The aim was a retrospective analysis of 12/14F ureteral access sheath (UAS) usage on perioperative outcomes in patients with moderate nephrolithiasis (MN). MN was defined as a maximum of two unilateral kidney stones with a maximum stone diameter of 6-10 mm. MATERIAL AND METHODS: We conducted a monocentric retrospective univariate and multivariate analysis of flexible ureteroscopies (fURS) performed for MN between 01/2014 and 12/2018. RESULTS: A total of 402 fURS were performed in patients with urolithiasis; 112 MN cases underwent further analysis. UAS was successfully applied in 33 MN cases [33/112 (29.46%)]. UAS was inserted regardless of the maximum kidney stone diameter and the presence of multiple kidney stones (p > 0.05). Univariate analysis revealed a prolonged median operation time (UAS: 94 min, non-UAS: 74 min, p = 0.04) and median fluoroscopy time (UAS: 75 s, non-UAS: 57.5 s, p = 0.04) in the UAS cohort. These differences were not confirmed on multivariate logistic regression.UAS was not associated with better stone-free rates in either the univariate or multivariate analysis (UAS: 26/33, non-UAS: 61/79, p = 1.0) nor with the occurrence of Clavien-Dindo ≥2 complications (UAS: 3/33, non-UAS: 9/79, p = 0.98) or median length of hospital stay (UAS: 2 days, non-UAS: 2 days, p = 0.169). CONCLUSION: We identified no statistical benefits from the usage of 12/14F UAS for MN. As no relevant UAS-associated complications were documented, both strategies (with and without UAS) are feasible.

Theoretical and experimental evaluation of the distance dependence of fiber-based fluorescence and reflection measurements for laser lithotripsy.

Objectives. In laser lithotripsy, a green aiming beam overlying the infrared (IR) treatment radiation gives rise to reflection and fluorescence signals that can be measured via the treatment fiber. While stone autofluorescence is used for target detection, the condition of the fiber can be assessed based on its Fresnel reflection. For good applicability, fluorescence detection of stones should work even when the stone and fiber are not in direct contact. Fiber breakage detection, on the other hand, can be falsified if surfaces located in front of the fiber reflect light from the aiming laser back into it. For both applications, therefore, a fundamental investigation of the dependence of the signal amplitude on the distance between fiber and surface is important.Methods. Calculations of the signal drop of fluorescence or diffuse and specular reflection with increasing fiber distance were performed using ray tracing based on a simple geometric model for different fiber core diameters. Reflection signals from a mirror, diffuse reflector, human calculi, and porcine renal tissue placed in water were measured at varying distances (0-5 mm). For human calculi, fluorescence signals were recorded simultaneously.Results. The calculations showed a linear signal decrease down to ∼60% of the maximum signal (fiber in contact). The distancezat which the signal drops to for example 50% depends linearly on the diameter of the fiber core. For fibers used in lithotripsy and positioned in water,z50%ranges from 0.55 mm (200µm core diameter) to 2.73 mm, (1 mm core diameter). The calculations were in good agreement with the experimental results.Conclusions. The autofluorescence signals of stones can be measured in non-contact mode. Evaluating the Fresnel signal of the end face of the fiber to detect breakage is possible unless the fiber is situated less than some millimeters to reflecting surfaces.

[Osteoprotection in the management of metastatic prostate cancer: real-world data from Germany and decision guidance]. / Osteoprotektion als Baustein der Therapie des metastasierten Prostatakarzinoms: Behandlungsrealität in Deutschland und Entscheidungspfade zur Therapieoptimierung.

OBJECTIVE: Osteoprotective medications are a key element not only in the management of bone metastases of castration-resistant prostate cancer (mCRPC) but also of hormone-sensitive prostate cancer (mHSPC). Additionally, osteoprotective drugs can prevent androgen deprivation-induced bone loss. The aim of this study was to illustrate the practice pattern of osteoprotection for prostate cancer patients in Germany. MATERIAL AND METHODS: We designed an online survey consisting of 16 questions. The survey was sent to the nation-wide working groups "Oncology" and "Uro-Oncology" as well as to colleagues from the departments of urology of University Hospital Schleswig-Holstein (Campus Lübeck), Academic Hospital Brunswick and Technical University of Munich. Furthermore, we developed flow charts for decision guidance for osteoprotection within the different stages of prostate cancer. RESULTS: Our analysis demonstrates a routine use of osteoprotection in the management of bone metastases of mCRPC. In contrast, osteoprotective medications are less often used for the treatment of bone metastases of mHSPC and for the prevention of androgen deprivation-induced bone loss. Our flow charts depict the different dosages and intervals for the administration of osteoprotective drugs in the different stages of prostate cancer. CONCLUSIONS: Osteoprotection is not only confined to mCRPC with bone metastases. It plays a crucial role in the management of all stages of metastatic prostate cancer.