[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.

[Systemic therapy for mHSPC: doublet or triplet therapy - who, when and how?] / Medikamentöse Tumortherapie des mHSPC: Double- oder Tripletherapie: wer, wann und wie?

At present, androgen deprivation therapy (ADT) as monotherapy for metastatic hormone-sensitive prostate cancer (mHSPC) should be an exception. The new standard of care is a doublet combination consisting of ADT + a new hormonal agent (NHA) or ADT + chemotherapy. Contemporary investigations even recommend a triplet therapy consisting of ADT + NHA + chemotherapy for selected mHSPC patients. The current evolution of mHSPC therapy demands a pretherapeutic classification of mHSPC: "low" vs. "high risk", "low" vs. "high volume" and synchronous vs. metachronous mHSPC. Additionally, attention should be paid to the drug specific side effects and especially whether the patient is fit for chemotherapy. This article gives a concise overview of the key clinical trials, current guideline recommendations and drug approvals for Germany.

Enfortumab vedotin as a salvage option as 5th line therapy for metastatic urothelial bladder cancer.

A 67-year-old female patient with a muscle-invasive, non-metastatic urothelial bladder cancer (UC) (pT2 G3 cN0 cM0) developed metachronous metastases within 6 months after radical cystectomy with ileal conduit urinary diversion. After a good primary response to platinum-based chemotherapy, treatment was switched to the immune checkpoint inhibitor (ICI) pembrolizumab due to progressive disease. Subsequently the patient underwent selective internal radiotherapy (SIRT) of the liver and received vinflunine as well as a re-challenge with pembrolizumab. Two years after the initial diagnosis, rapid disease progression ultimately led to a switch to 5th line therapy with enfortumab vedotin (EV), which had only been approved in the United States at that time. The antibody-drug conjugate was well tolerated by the patient after dose reduction to 1.0 mg/ kg body weight. Simultaneous irradiation of newly occurring precardiac, hepatic and cerebral metastases were necessary. After 10 months of therapy with EV, tumour regression was observed accompanied with good symptom control. The presented case illustrates the efficacy and tolerability of EV in a heavily pre-treated patient with metastatic UC (mUC).

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.

Advanced delivery of leuprorelin acetate for the treatment of prostatic cancer.

INTRODUCTION: Androgen-deprivation therapy (ADT) is the main therapy for patients with advanced and metastatic prostate cancer (PCa) and, in combination with radiotherapy, for patients with localized high-risk PCa. Due to its favorable tolerability among different treatments available for ADT, leuprorelin acetate is well established as the leading luteinizing hormone-releasing hormone (LHRH) analog. The development of second-generation leuprorelin acetate (LA) depot formulation (Eligard®, Recordati S.p.A) allowed a consistent and controlled release of leuprorelin between injections and a more efficient reduction of testosterone levels with respect to conventional LHRH agonists. AREAS COVERED: This work provides a summary of the biological and clinical rationale for using LA to manage PCa and presents the current evidence about the therapeutic activity of the LA gel depot formulation, used as an advanced leuprorelin acetate delivery method. EXPERT OPINION: Results of the registration studies and post-marketing clinical trials demonstrate that the LA gel depot provides long-term efficacy in the clinical practice and a good degree of tolerability. Overall, collected data suggest that the LA gel depot can represent the ADT reference therapy in advanced PCa.