Therapeutic Advances in Urology最新文献

DNA repair genomic aberrations in the Homologous Recombination pathway are identifiable in up to 25% of patients with advanced prostate cancer, making them more likely to benefit from treatment with poly (ADP-ribose) polymerase inhibitors (PARPi) alone or in combination with other therapies, particularly when BRCA driver genomic aberrations are documented. Although several clinical trials have demonstrated the efficacy of this approach, the validation of reliable biomarkers predictive of response still needs further improvement to refine patient selection. In this setting, the characterization of resistance mechanisms and the validation of novel biomarkers are critical to maximize clinical benefit and to develop novel treatment combinations to improve outcomes. In this review, we summarize the development of PARPi in prostate cancer as single agent as well as the efficacy of their combination with other drugs, and the future directions for their implementation in the management of advanced prostate cancer.

Background: In vitro studies have shown that the holmium Modulated Optics Enhancement Systems (MOSES) technology can lead to an increase in the efficacy of lithotripsy and a reduction of retropulsion, but clinical evidence comparing it to non-MOSES technology is still scarce. We did a comparison of ureteoroscopy and laser stone fragmentation (URSL) between Holmium:YAG laser with MOSES versus non-MOSES technologies.

Methods: Patient data and outcomes were prospectively collected and analyzed regarding patient demographics, stone parameters, and clinical outcomes. Patients undergoing URSL with standard holmium laser without MOSES technology (Group 1) were compared to holmium laser with MOSES (Group 2) using the same clinical laser settings (0.4-1 J, 20-40 Hz) with dusting and pop-dusting technique. The independent t-test, Mann-Whitney U test, and Chi-squared test were used, with a p-value of < 0.05 as significant. Given the different sizes of the cohorts, we performed a propensity score 1:1 matched analysis.

Results: A total of 206 patients (1:1 matched) with a male:female ratio of 94:112 and a median age of 56 (range: 39-68) years were analyzed. Groups 1 and 2 were matched for ureteric stones (27.7% and 22.3%, p = 0.42), pre-stenting (37% and 35%, p = 0.66), the mean number of stones (1.76 ± 1.3) and (1.82 ± 1.4, p = 0.73), and ureteral access sheath use (37% and 35%, p = 0.77) respectively.While there was no significant statistical difference in clinical outcomes, the stone size was slightly larger in Group 2, 14.8 ± 10.8 mm vs 11.7 ± 8.0 mm, for a lower operative time 42.7 ± 30.6 min versus 48.5 ± 25 min, lower perioperative complication rates 3.9% versus 4.9% and a higher stone-free rate 90.3% versus 87.4%.

Conclusion: While the use of MOSES technology was slightly beneficial for the treatment of stones in terms of clinical outcomes, this was not statistically significant. As this debate continues, there is a need for high-quality randomized studies to show if there is a true difference in these outcomes.

Introduction: Modulated optics enhancement system (MOSES) holmium lasers use "pulse modulation" to increase the efficacy of laser lithotripsy. As the clinical evidence on the efficacy of 60 W holmium laser with MOSES technology is scarce, we analyzed the outcomes of patients treated with this laser at our institution.

Methods: A total of 96 consecutive patients with urinary stones (72 renal stones and 24 ureteral stones) were treated with the 60 W MOSES laser from 2019 until 2022 and were included in our analysis. Patient data and outcomes were prospectively collected, and analysis was performed regarding patient demographics, stone parameters, as well as stone-free rate, operating time, length of stay, and perioperative and postoperative complications.

Results: With a median age of 55 (IQR: 35-69.25) years, the male:female ratio was 53:43. The median stone size was 12 mm (IQR: 7-19), with a mean number of urinary stones of 1.82 (SD ± 1.4). While 36 (35%) patients were pre-stented, a ureteral access sheath was inserted in 36 (37.5%) patients. The median operative time was 44 min (IQR: 22.5-59.5), and 63 (65.5%) patients received postoperative stenting. Perioperative complications (all Clavien ⩽ II complications) were observed in 5 (5.2%) patients (four urinary tract infections and one acute urinary retention), and after the first procedure, 90 (93.8%) patients were stone-free. The median length of hospital stay was 1 day (IQR: 1-1).

Conclusion: This study demonstrated that the 60 W MOSES laser was safe and efficient for the treatment of urinary stones with high stone-free rates and a small risk of minor complications. More studies with larger cohorts are necessary in the future to confirm our results.

Bladder paraganglioma is a rare neuroendocrine neoplasm, either functional or non-functional, arising from the urinary bladder. Functional variants present with catecholamine-related symptoms, while non-functional variants pose diagnostic challenges, mimicking urothelial carcinoma. Misdiagnosis risks underscore the importance of accurate identification for appropriate patient management. In this case, a 52-year-old man, diagnosed incidentally with hypertension and reported occasional post-micturition tachycardia, underwent abdominal ultrasound for known hepatic cyst follow-up, revealing an oval hypoechoic bladder mass. Initial consideration of bladder urothelial carcinoma prompted further investigation with contrast-enhanced CT scan and cystoscopy that confirmed extrinsic mass nature, and subsequent robotic-assisted partial cystectomy was performed. Histologically, the removed mass exhibited characteristic features of bladder paraganglioma. Postoperative recovery was uneventful, with resolution of post-micturition tachycardia at 1 month. Follow-up includes endocrinological evaluation and a 6-month CT scan. In conclusion, bladder paraganglioma should be considered in para-vesical mass differentials. This case highlights the importance of meticulous history collection, even in asymptomatic patients, the need for a multidisciplinary approach for accurate diagnosis and management of this rare condition, and the robotic approach as a viable option.

Antibody-drug conjugates and bicycle toxin conjugates represent a tremendous advance in drug delivery technology and have shown great promise in the treatment of urothelial cancer. Previously approved systemic therapies, including chemotherapy and immunotherapy, are often impractical due to comorbidities, and outcomes for patients with advanced disease remain poor, even when receiving systemic therapy. In this setting, antibody-drug and bicycle toxin conjugates have emerged as novel treatments, dramatically altering the therapeutic landscape. These drugs harness unique designs consisting of antibody or bicycle peptide, linker, and cytotoxic payload with more targeted delivery than conventional chemotherapy, thus eliminating malignant cells while reducing systemic toxicities. Potential targets investigated in urothelial cancer include Nectin-4, TROP2, HER2, and EphA2. Initial clinical trials demonstrated efficacy in treatment of refractory advanced urothelial cancer, as well as improvement in quality of life. These initial studies led to FDA approval of two antibody-drug conjugates, enfortumab vedotin and sacituzumab govitecan. Moreover, antibody-drug and bicycle toxin conjugates are being studied in ongoing clinical trials in frontline treatment of advanced disease as well as for localized cancer. These studies highlight the potential for additional future therapies with novel targets, novel antibodies, cytotoxic and immunomodulatory payloads, and unique structural designs enhancing efficacy and safety. There is increasing evidence that combinations with other cancer therapies, especially immunotherapy, improve treatment outcomes. The combination of enfortumab vedotin and pembrolizumab was recently approved for first-line treatment of advanced urothelial carcinoma. Despite the great promise of these novel drugs, robust predictive biomarkers are needed to determine the patients who would maximally benefit. This review surveys the rationale and current state of the evidence for these new drugs and describes future directions actively being explored.

Introduction: Sexual dysfunction is highly prevalent among men of reproductive age. Clinical practice guidelines have been established to assist providers in identification and education of patients who are at increased risk for infertility and sexual dysfunction with certain congenital and acquired urogenital disorders. The authors sought to review the reproductive and sexual health implications of treating common childhood urological conditions with commonly performed surgical procedures.

Methods: To ensure the inclusion of influential and highly regarded research, we prioritized citations from the most-frequently cited articles on our respective review topics. Our inclusion criteria considered studies with substantial sample sizes and rigorously designed methodologies. Several topics were reviewed, including penile chordee, hypospadias, posterior urethral valves, varicoceles, undescended testicles, and testicular torsion.

Results: For chordee, surgical plication or corporal grafting may be employed. Erectile function remains unaltered post-surgery, while penile length may decrease after repair, which may be avoided using dermal grafts. Hypospadias repair hinges on severity and availability of the urethral plate. Those who underwent hypospadias repair report decreased penile length, but sexual satisfaction, libido, and semen quality are comparable to controls. Posterior urethral valves are usually treated with valve ablation. While valve ablation and bladder neck incision have not been found to affect ejaculatory function, high degree of concurrent renal dysfunction related to nephrogenic and bladder dysfunction may impact semen parameters and erectile function. Regarding varicocele, earlier management has been associated with better long-term fertility outcomes, and surgical intervention is advisable if there is observable testicular atrophy. Earlier repair of undescended testicle with orchiopexy has been found to improve fertility rates as well as decrease malignancy rates. Unilateral orchiectomy for testicular torsion without the ability for salvage has been shown to have decreased semen parameters but unaffected fertility rates.

Conclusion: Infertility and sexual dysfunction are multivariable entities, with etiologies both congenital and acquired. At the same time, many common pediatric urology surgeries are performed to correct anatomic pathology that may lead to reproductive dysfunction in adulthood. This review highlights the need for diagnosis and management of pediatric urologic conditions as these conditions may impact long-term sexual function post-operatively.