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There is a high medical need to develop new strategies for the treatment of patients with acute myeloid leukemia (AML) refractory to conventional therapy. In vitro, the combinations of the blast-modulatory response modifiers GM-CSF + Prostaglandin E1, (summarized as Kit M) have been shown to convert myeloid leukemic blasts into antigen-presenting dendritic cells of leukemic origin (DC leu ) that were able to (re-)activate the innate and adaptive immune system, direct it specifically against leukemic blasts, and induce memory cells. This study aimed to investigate the immune modulatory capacity and antileukemic efficacy of Kit M in vivo. Brown Norway rats suffering from AML were treated with Kit M (twofold application). Blasts and immune cells were monitored in peripheral blood (PB) and spleen. Upon the observation of promising immune modulatory effects in the treated animals, two patients with AML refractory to multiple lines of therapy were offered treatment with Kit M on an individualized basis. Safety, as well as immunological and clinical effects, were monitored. Samples obtained from a third patient in similar clinical conditions not receiving Kit M were used as controls for immune monitoring tests. Animal experiments : Drugs were well tolerated by the treated animals. After 9 days of treatment, DC leu and memory-like T cells increased in the peripheral blood, whereas regulatory T cells, especially blasts, decreased in treated as compared to untreated control animals. Clinical courses : No severe side effects were observed. In patient 1482, PB blasts remained under the detection threshold during 27 days of treatment, thrombocytes were normalized, and (leukemia specific) immune effector cells of the adaptive and innate immune system increased up to 800-fold compared to the start of treatment. Patient 1601 responded with a 12% reduction in blasts in PB immediately after Kit M treatment. Several subtypes of (leukemia-specific) immune effector cells in PB increased up to four-fold during the 19 days of treatment. In contrast, immune-reactive cells decreased under mild chemotherapy in the PB of control patient 1511 with comparably refractory AML. Within the limitation of low numbers in both animal experiments and clinical applications, our data suggest that Kit M treatment of AML-diseased rats and patients is feasible and may induce leukemia-specific immune reactions and clinical improvement. A larger series and a prospective clinical trial will be required to confirm our observations. Beyond optimized doses and schedules of the applied compounds, the combination with other antileukemic strategies or the application of Kit M in less proliferative stages of the myeloid diseases need to be discussed. If effects are confirmed, the concept may add to the armamentarium of treatments for highly aggressive blood cancer.

Multiparametric magnetic resonance imaging (mpMRI) has emerged as a new cornerstone in the diagnostic pathway of prostate cancer. However, mpMRI is not devoid of factors influencing its detection rate of clinically significant prostate cancer (csPCa). Amongst others, prostate volume has been demonstrated to influence the detection rates of csPCa. Particularly, increasing volume has been linked to a reduced cancer detection rate. However, information about the linkage between PI-RADS, prostate volume and detection rate is relatively sparse. Therefore, the current study aims to assess the association between prostate volume, PI-RADS score and detection rate of csP-Ca, representing daily practice and contemporary mpMRI expertise. Thus, 1039 consecutive patients with 1151 PI-RADS targets, who underwent mpMRI-guided prostate biopsy at our tertiary referral center, were included. Prior mpMRI had been assessed by a plethora of 111 radiology offices, including academic centers and private practices. mpMRI was not secondarily reviewed in house before biopsy. mpMRI-targeted biopsy was performed by a small group of a total of ten urologists, who had performed at least 100 previous biopsies. Using ROC analysis, we defined cut-off values of prostate volume for each PI-RADS score, where the detection rate drops significantly. For PI-RADS 4 lesions, we found a volume > 61.5 ccm significantly reduced the cancer detection rate (OR 0.24; 95% CI 0.16-0.38; p < 0.001). For PI-RADS 5 lesions, we found a volume > 51.5 ccm to significantly reduce the cancer detection rate (OR 0.39; 95% CI 0.25-0.62; p < 0.001). For PI-RADS 3 lesions, none of the evaluated clinical parameters had a significant impact on the detection rate of csPCa. In conclusion, we show that enlarged prostate volume represents a major limitation in the daily practice of mpMRI-targeted biopsy. This study is the first to define exact cut-off values of prostate volume to significantly impair the validity of PI-RADS assessed in a real-world setting. Therefore, the results of mpMRI-targeted biopsy should be interpreted carefully, especially in patients with prostate volumes above our defined thresholds.

Objective: Over the last decade, active surveillance (AS) of low-risk prostate cancer has been increasing. The mpMRI fusion-guided biopsy of the prostate (FBx) is considered to be the gold standard in preoperative risk stratification. However, the role of FBx remains unclear in terms of risk stratification of low-risk prostate cancer outside high-volume centers. The aim of this study was to evaluate adverse pathology after radical prostatectomy (RP) in a real-world setting, focusing on patients diagnosed with Gleason score (GS) 6 prostate cancer (PCa) and eligible for AS by FBx., Subjects and Methods: Between March 2015 and March 2022, 1297 patients underwent FBx at the Department of Urology, Ludwig-Maximilians-University of Munich, Germany. MpMRI for FBx was performed by 111 different radiology centers. FBx was performed by 14 urologists from our department with different levels of experience. In total, 997/1297 (77%) patients were diagnosed with prostate cancer; 492/997 (49%) of these patients decided to undergo RP in our clinic and were retrospectively included. Univariate and multivariable logistic regression analyses were performed to evaluate clinical and histopathological parameters associated with adverse pathology comparing FBx and RP specimens. To compare FBx and systematic randomized biopsies performed in our clinic before introducing FBx (SBx, n = 2309), we performed a propensity score matching on a 1:1 ratio, adjusting for age, number of positive biopsy cores, and initial PSA (iPSA)., Results: A total of 492 patients undergoing FBx or SBx was matched. In total, 55% of patients diagnosed with GS 6 by FBx were upgraded to clinically significant PCa (defined as GS ≥ 7a) after RP, compared to 52% of patients diagnosed by SBx ( p = 0.76). A time delay between FBx and RP was identified as the only correlate associated with upgrading. A total of 5.9% of all FBx patients and 6.1% of all SBx patients would have been eligible for AS ( p > 0.99) but decided to undergo RP. The positive predictive value of AS eligibility (diagnosis of low-risk PCa after biopsy and after RP) was 17% for FBx and 6.7% for SBx ( p = 0.39)., Conclusions: In this study, we show, in a real-world setting, that introducing FBx did not lead to significant change in ratio of adverse pathology for low-risk PCa patients after RP compared to SBx.

Introduction: International Prostate Symptom Score (IPSS) is a validated outcome measure for the evaluation of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). When treating patients with transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP), patient selection is key to achieve the best clinical outcome. Therefore, we analyzed how the severity of LUTS as determined by IPSS influenced postoperative functional outcomes., Material and Methods: We conducted a retrospective, matched-pair analysis of 2,011 men who underwent HoLEP or TURP for LUTS/BPO between 2013-2017. We included 195 patients in the final analysis (HoLEP n = 97; TURP n = 98), who were matched for prostate size (50 cc), age, and body mass index. Patients were then stratified by IPSS. Groups were compared for perioperative parameters, safety and short-term functional outcomes., Results: While preoperative symptom severity was a significant predictor of postoperative clinical improvement, patients who received HoLEP showed superior postoperative functional results with higher peak flow rates and 2-fold greater improvement in IPSS. In patients presenting with severe symptoms, we observed 3- to 4-fold less Clavien-Dindo grade ≥II and overall complications after receiving HoLEP compared to TURP., Conclusions: Patients with severe LUTS were more likely to experience clinically significant improvement after surgery than patients with moderate LUTS, and HoLEP showed superior functional outcomes than TURP. However, patients with moderate LUTS should not be denied surgery, but may warrant a more comprehensive clinical work-up., Competing Interests: The authors declare no conflicts of interest., (Copyright by Polish Urological Association.)

Introduction: Medical treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) targets prostate size, to prevent disease progression, and prostate smooth muscle tone for rapid relieve of LUTS. Holmium laser enucleation of the prostate (HoLEP) is a size-independent method for surgical treatment of LUTS/BPO in medication-refractory patients and offers durable long-term results with reduced perioperative morbidity. As up to 50% of patients receive medical treatment for LUTS/BPO prior to surgery, we analyzed the impact of alpha-blockers and 5-alpha reductase inhibitors (5-ARI) on outcomes and perioperative morbidity in patients undergoing HoLEP for LUTS., Material and Methods: We retrospectively gathered data of 1,057 patients, who underwent HoLEP for LUTS/BPO from 2013-2018, and divided patients into group 1 (no medication), group 2 (α-blockers), and group 3 (5-ARI and α-blockers). Perioperative parameters, short-term functional outcomes and safety were assessed and statistical analysis was performed using SPSS V26.0 software., Results: Even though preoperative LUTS profile was significantly different between groups, all patients improved significantly after HoLEP, irrespective of preoperative LUTS medication. Median improvement of IPSS was 9, 8 and 7 points, of Q max was 10, 12 and 9.5 ml/s, with significant improvement of quality of life (QoL) and reduction of post-void residual volume (PVR) for groups 1-3, respectively, 30 days after surgery. With only 4.0% (42/1,057) of patients experiencing a Clavien-Dindo grade ≥II complication, there was no difference in prevalence of perioperative complications between groups (p = 0.943)., Conclusions: Although preoperative LUTS medication does not impair efficacy of HoLEP with acceptable perioperative morbidity, the time gap between medical therapy and surgical treatment may favor an earlier response., Competing Interests: The authors declare no conflicts of interest., (Copyright by Polish Urological Association.)