The effect of intravesical chemohyperthermia with mitomycin in non-muscle-invasive bladder tumour patients who cannot tolerate BCG treatment or recur after treatment and refuse cystectomy.

PURPOSE: Many patients receiving intravesical BCG treatment for non-muscle-invasive bladder cancer experience high recurrence rates despite initial adequate response. In this study, the effectiveness of intravesical chemohyperthermia (CHT) with mitomycin C (MMC) was evaluated in patients who developed relapse after intravesical BCG treatment or could not tolerate the treatment and could not undergo radical cystectomy for any reason. MATERIALS AND METHODS: 59 patients who underwent complete bladder tumour resection, who had a T1 high-grade tumour and no variant histology was observed in the pathology, and who had previously received intravesical BCG treatment were included in the study. Adjuvant treatment with intravesical CHT-MMC was applied. As a treatment protocol, induction was applied once a week for 6 weeks, followed by maintenance treatment 6 times at 4-week intervals. Each treatment session, it involved bladder wall hyperthermia with a temperature of up to 42 â„ƒ ± 2 and intravesical administration of 20 mg/50 ml MMC solution twice at 30-min intervals. RESULTS: Recurrence-free survival after warm mitomycin was 58.7 and 48%, respectively, at 24 months and 44 months, and progression-free survival was 72.6 and 66.2%, respectively. In the subgroup analysis performed according to the number of tumours at diagnosis (single, 2-5, more than 5), recurrence-free survival rates were 81.8%, 48.2% and 11%, respectively, during the median follow-up period of 44 months. CONCLUSIONS: Intravesical CHT-MMC can be considered as an alternative treatment in selected well-informed patients with non-muscle-invasive papillary urothelial carcinoma who are unresponsive to BCG or intolerant to BCG. Prospectively designed studies with larger number of patients are needed.

The role of immunotherapy in urological cancers.

Immunotherapy is defined as a therapeutic approach that targets or manipulates the immune system. A deeper understanding of the cellular and molecular composition of the tumour environment, as well as the mechanisms controlling the immune system, has made possible the development and clinical investigation of many innovative cancer therapies. Historically, immunotherapy has played an essential role in treating urologic malignancies, while in the modern era, the development of immune checkpoint inhibitors (ICIs) has been critical to urology. Urothelial carcinoma is a common type of cancer in the genitourinary system, and treatment strategies in this area are constantly evolving. Intravesical and systemic immunotherapeutic agents have begun to be used increasingly frequently in treating urothelial carcinoma. These agents increase the anti-tumour response by affecting the body's defence mechanisms. Immunotherapeutic agents used in urothelial carcinoma include various options such as BCG, interferon, anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 (atezolizumab, avelumab, durvalumab). Renal cell carcinoma (RCC) has been known for many years as a tumour with unique sensitivity to immunotherapies. The recent emergence of ICIs that block PD-1/PD-L1 (pembrolizumab, nivolumab, atezolizumab) or CTLA4 (ipilimumab) signalling pathways has reestablished systemic immunotherapy as central to the treatment of advanced RCC. In light of randomized clinical trials conducted with increasing interest in the application of immunotherapies in the adjuvant setting, combination therapies (nivolumab/ipilimumab, nivolumab/cabozantinib, pembrolizumab/ axitinib, pembrolizumab/lenvantinib) have become the standard first-line treatment of metastatic RCC. Prostate cancer is in the immunologically "cold" tumour category; on the contrary, in recent years, immunotherapeutic agents have come to the fore as an essential area in the treatment of this disease. Especially in the treatment of castration-resistant prostate cancer, immunotherapeutic agents constitute an alternative treatment method besides androgen deprivation therapy and chemotherapy. Ipilimumab, nivolumab, pembrolizumab, atezolizumab, and Sipuleucel T (Vaccine-based) are promising alternative treatment options. Considering ongoing randomized clinical trials, immunotherapeutic agents promise to transform the uro-oncology field significantly. In this review, we aimed to summarize the role of immunotherapy in urothelial, renal and prostate cancer in the light of randomized clinical trials.

The prognostic value of expressions of STAT3, PD-L1, and PD-L2 in Ta/T1 urothelial carcinoma before and after BCG treatment.

INTRODUCTION: Nonmuscle invasive bladder cancers (NMIBC) are common tumors diagnosed in older individuals and men (median age: 69 years). Immunotherapy is a treatment option in cases resistant to Bacillus-Calmette-Guerin (BCG) therapy. We aimed to evaluate the prognostic role of programmed-cell-death ligand (PD-L)-1 (PD-L1), PD-L2, and signal transducer and activator of transcription 3 (STAT3) expressions, which are closely related to immune mechanisms, in the response to BCG treatment of NMIBC. METHODS: The data of patients at the Ta and T1 stages of the cancer without muscularis propria invasion, who were treated with intravesical BCG therapy between 2017 and 2022 were retrospectively analyzed. Immunohistochemical staining for PD-L1, PD-L2, and STAT3 was performed on transurethral resection materials. RESULTS: The mean age of 59 patients was 66.5 ±7.7 and 83.9% were male. The percentage of patients with complete response to BCG treatment was 66.1% and that of BCG refractory patients was 33.9%. Demographic and clinical data did not differ significantly according to BCG treatment response (P> 0.05). The proportion of patients with tumor-infiltrating lymphocytes (TILs) ≥20% were 9.7% among those with Ta-stage tumors and 46.4% among those with T1-stage tumors (P = 0.0014). The percentages of tumor cell scoring (TCS), immune cell scoring (ICS), combined scoring (CS), and expression levels of PD-L1, PD-L2, and H-score of STAT3 did not differ significantly according to tumor stage and treatment response (P > 0.05). However, the median ICS and CS for PD-L1 and median H-score for STAT3 were significantly higher among patients in T1 stage compared to those in Ta stage (P = 0.0487, 0.0462, 0.0112, respectively). Among BCG refractory patients, median STAT3 of patients in T1 stage was significantly higher than those at stage Ta (P = 0.0356) and the rate of TILs was ≥20% in only 3 patients in T1 stage (P = 0.031). Among all patients, significant positive correlation was found between TCS for PD-L1 and H-score for STAT3 (P = 0.0302); and between ICS for PD-L1 and TCS for PD-L2 (P = 0.0053) and TILs ratio (P < 0.0001). Among BCG-refractory cases, pretreatment and post-treatment TCS for PD-L2 and H-scores for STAT3 were significantly correlated (P = 0.0361 and 0.0021, respectively). CONCLUSIONS: The success of BCG treatment in NMIBC was not related to PD-L1, PD-L2, and STAT3 expression status, but PD-L1 expression was correlated with both PD-L2 and STAT3 as well as TILs rate, but this correlation was lost after BCG treatment.

Immediately repaired penile fractures: age is the only predictor of postoperative long-term functional outcomes.

Background: Penile fractures can lead to many functional complications, especially erectile dysfunction (ED). Few studies have evaluated the factors that predict late complications of an immediately repaired penile fracture. Aim: To identify the potential predictors of long-term poor functional outcomes following immediate surgical intervention for penile fractures. Methods: Sixty-eight consecutive patients with suspected penile fracture between 2003 and 2022 were retrospectively reviewed. Functional outcomes, postoperative complications, and follow-up duration were obtained from the records of follow-up visits. Age at presentation, location and length of the tunical tear, the presence of urethral rupture, and time to surgery were all analyzed as potential risk factors for postoperative functional outcomes. Outcomes: Postoperative erectile function and intercourse satisfaction were measured by the IIEF-5 (the 5-item version of the International Index of Erectile Function). Penile curvature, a palpable nodule, and paresthesia/numbness were detected by physical examination. Uroflowmetry was used to assess urinary flow in patients who underwent urethral repair. Results: Fifty-eight patients were analyzed. The mean ± SD age was 38.1 ± 10.4 years; the median follow-up was 79.0 months (range, 13-180); the median time to surgery was 9.8 hours (4-30); and the median tunical tear length was 15.5 mm (4-40). Urethral rupture was observed in 8 patients (13.8%). In univariable analyses, urethral rupture was associated with postoperative complications (P = .034). In addition, age at presentation and tunical tear size were significantly associated with postoperative complications and ED (P < .05). However, in multivariable analyses, only age at presentation significantly predicted postoperative complications and ED (P = .004 and P = .037). Clinical Implications: Age at presentation is the most important factor determining the prognosis of immediate surgical repair of the penile fracture, which aids in predicting potential complications and discussing them with patients prior to surgical intervention and during the follow-up period. Strengths and Limitations: The study's retrospective design is an important limitation. Furthermore, there were no data on an IIEF-5 outcome measuring preoperative erectile function. Conclusion: These results revealed an association between (1) urethral rupture, longer tunical tears, and older age and (2) the development of late complications. The remarkable finding of this study was that age at presentation was the only significant predictor of functional complications based on multivariable analyses. This relationship also remained robust in tests evaluating the covariance of the effects of aging on ED.

Evaluation of comprehensive complication index versus Clavien-Dindo classification in prediction of overall survival after radical cystectomy.

PURPOSE: We aimed to evaluate the benefits of Comprehensive Complication Index (CCI) compared with the Clavien-Dindo Classification (CDC) in the reporting of radical cystectomy (RC) complications. MATERIALS AND METHODS: We retrospectively analyzed post-operative complications of 251 consecutive RC patients between 2009 and 2021. Patient demographics and causes of mortality were noted. Oncologic outcomes included the recurrence, time to recurrence, cause of all deaths, and time to death. Each complication was graded with CDC and, corresponding and cumulative CCI calculated for each patient. RESULTS: A total of 211 patients are included. Median patient age and follow-up time were 65 (IQR 60-70) years and 20 (IQR 9 - 53) months, respectively. The five-year recurrence and death rates were 39.3% (83/211) and 59.7% (126/211), respectively. Post-operative 521 complications were recorded. Patients with experienced any complication were 69.6% (147/211) and 45.0% (95/211) had > 1 complications. Thirty (14.2%) patients ended up with a cumulative CCI score that corresponded to a higher CDC grade. Severe complications calculated with CDC increased from 18.5% to 19.9% (p < 0.001) with cumulative CCI. Female gender, positive lymph node, and positive surgical margin, presence of severe CDC complication, and CCI score were significant independent predictive factors for overall survival (OS). The contribution of CCI to the multivariable model was 1.8% higher than CDC. CONCLUSIONS: Cumulative morbidity reporting improved with the use of CCI compared to CDC. Both CDC and CCI are significant predictive factors for OS independent of oncologic predictive factors. Reporting the cumulative burden of complications with CCI is more predictive on oncologic survival than reporting complications with CDC.

Urethral rupture concomitant with penile fracture does not adversely affect functional outcomes.

INTRODUCTION: The aim of this study was to identify possible risk factors for urethral rupture and to evaluate the effect of urethral rupture repair on long-term functional outcomes and complications. MATERIALS AND METHODS: The medical records of consecutive penile fracture patients were retrospectively reviewed. Penile fracture patients with and without urethral rupture were compared according to demographics, clinical and intraoperative findings. Comparisons of postoperative functional results of the groups were performed using the 5-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (IPSS). Finally, among them, long-term penile complications including penile curvature, painful erection, palpable nodule, and paresthesia were assessed. RESULTS: Fifty-three patients participated. Patients with urethral rupture (n = 8) were older (44.50 ± 10.69, 36.58 ± 10.33 years, p = 0.052). There was no significant difference in fracture etiology (p = 0.64). Urethral bleeding was present only in patients with urethral rupture (p < 0.001). Although no bilateral corpus cavernosum rupture was encountered in penile fracture patients without urethral rupture, this rate was significantly higher in those with urethral rupture at a rate of 62.5% (p < 0.001). The time from surgical repair to sexual activity was similar in both groups (p = 0.66). There was no significant difference in IPSS and IIEF-5 scores, the presence of erectile dysfunction and complication rates (p > 0.05). CONCLUSIONS: Older age is a possible risk factor for a concomitant urethral rupture with penile fracture and it seems to be associated with urethral bleeding and bilateral corpus cavernosum involvement. Additionally, urethral rupture repair neither adversely affected functional outcomes nor increased penile complication rates.

Oncological and functional outcomes of patients who underwent open partial nephrectomy for kidney tumor.

OBJECTIVE: To report long-term functional and oncological outcomes of OPN Methods: We enrolled 182 patients who underwent consecutive OPN with a diagnosis of kidney tumor in our clinic between April 2002 and February 2020 and were selected from our prospective OPN database. Preoperative demographic and clinical characteristics, intraoperative and pathological results, and patients' postoperative functional and oncological follow-up data were retrospectively analyzed. Overall survival (OS) and disease- free survival (DFS) were evaluated using Kaplan-Meier survival analysis. The time-dependent variation between preoperative and postoperative functional results was statistically analyzed and presented in a graph. RESULTS AND LIMITATIONS: The mean age was 54.4 ± 10.8 yr, and the median age-adjusted Charlson comorbidity index (ACCI) was 1 (interquartile range [IQR] 0-1). The mean tumor size was 3.1 ± 1.2 cm, and the median RENAL score was 6 (IQR 5-8). The most common malign histopathological subtype was clear cell carcinoma with 76.6%, and five cases (3.4%) had positive surgical margins (PSMs). The most common surgical techniques were the retroperitoneal approach (98.9%) and cold ischemia (88.5%). Estimated glomerular filtration rate (eGFR) preservation was 92% (80.8-99.3, IQR), which translates to 32% chronic kidney disease (CKD) upstaging. Acute kidney injury (AKI) was detected in 27 (14.8%) patients according to RIFLE criteria. The intraoperative complication rate was 5.5%, and the postoperative overall complication rate (Clavien-Dindo 1-5) was 30.2%. Major complications (Clavien-Dindo 3-5) were observed in 13 (7.1%) patients. The median oncological follow-up was 42 mo (21.3- 84.6, IQR), and the 5- and 10-yr OS were 90.1% and 78.6%, 5 and 10-yr DFS were 99.4% and 92.1%, respectively. No local recurrence was observed in 5 (3.4%) patients with PSMs; only one had distant metastasis in the 8th postoperative month. The retrospective design, the small number of patients who underwent PN based on mandatory indication, and one type of surgical approach may limit the generalizability of our findings. CONCLUSIONS: This study confirms excellent long-term oncologic and functional outcomes after OPN in a cohort of patients selected from a single institution. In light of the information provided by the literature and our study, our recommendation is to push the limits of PN under every technically feasible condition in the treatment of kidney tumors to protect the kidney reserve and achieve near-perfect oncological results.