Conditional survival does not improve over time in metastatic castration-resistant prostate cancer patients undergoing docetaxel.

PURPOSE: To investigate the conditional overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel chemotherapy. METHODS: We used deidentified patient-level data from the Prostate Cancer DREAM Challenge database and the control arm of the ENTHUSE 14 trial. We identified 2158 chemonaïve mCRPC patients undergoing docetaxel chemotherapy in the five randomized clinical trials. The 6-month conditional OS was calculated at times 0, 6, 12, 18, and 24 months from randomization. Survival curves of each group were compared using the log-rank test. Patients were then stratified into low- and high-risk groups based on the median predicted value of our recently published nomogram predicting OS in mCRPC patients. RESULTS: Nearly half (45%) of the study population was aged between 65 and 74 years. Median interquartile range prostate-specific antigen for the overall cohort was 83.2 (29.6-243) ng/mL, and 59% of patients had bone metastasis with or without lymph node involvement. The 6-month conditional survival rates at 0, 6, 12, 18, and 24 months for the entire cohort were 93% (95% confidence interval [CI]: 92-94), 82% (95% CI: 81-84), 76% (95% CI: 73-78), 75% (95% CI: 71-78), and 71% (95% CI: 65-76). These rates were, respectively, 96% (95% CI: 95-97), 92% (95% CI: 90-93), 84% (95% CI: 81-87), 81% (95% CI: 77-85), and 79% (95% CI: 72-84) in the low-risk group and 89% (95% CI: 87-91), 73% (95% CI: 70-76), 65% (95% CI: 60-69), 64% (95% CI: 58-70), and 58% (95% CI: 47-67) in the high-risk group. CONCLUSION: The conditional OS for patients undergoing docetaxel chemotherapy tends to plateau over time, with the main drop in conditional OS happening during the first year from initiating docetaxel treatment. That is the longer a patient survives, the more likely they are to survive further. This prognostic information could be a useful tool for a more accurate tailoring of both follow-up and therapies. PATIENT SUMMARY: In this report, we looked at the future survival in months of patients with metastatic castration resistant prostate cancer on chemotherapy who have already survived a certain period. We found that the longer time that a patient survives, the more likely they will continue to survive. We conclude that this information will help physicians tailor follow-ups and treatments for patients for a more accurate personalized medicine.

Impact of preexisting opioid dependence on morbidity, length of stay, and inpatient cost of urological oncological surgery.

OBJECTIVES: To determine the incidence of preexisting opioid dependence in patients undergoing elective urological oncological surgery. In addition, to quantify the impact of preexisting opioid dependence on outcomes and cost of common urologic oncological procedures at a national level in the USA. METHODS: We used the National Inpatient Sample (NIS) to study 1,609,948 admissions for elective partial/radical nephrectomy, radical prostatectomy, and cystectomy procedures. Trends of preexisting opioid dependence were studied over 2003-2014. We use multivariable-adjusted analysis to compare opioid-dependent patients to those without opioid dependence (reference group) in terms of outcomes, namely major complications, length of stay (LOS), and total cost. RESULTS: The incidence of opioid dependence steadily increased from 0.6 per 1000 patients in 2003 to 2 per 1000 in 2014. Opioid-dependent patients had a significantly higher rate of major complications (18 vs 10%; p < 0.001) and longer LOS (4 days (IQR 2-7) vs 2 days (IQR 1-4); p < 0.001), when compared to the non-opioid-dependent counterparts. Opioid dependence also increased the overall cost by 48% (adjusted median cost $18,290 [IQR 12,549-27,715] vs. $12,383 [IQR 9225-17,494] in non-opioid-dependent, p < 0.001). Multivariable analysis confirmed the independent association of preexisting opioid dependence with major complications, length of stay in 4th quartile, and total cost in 4th quartile. CONCLUSIONS: The incidence of preexisting opioid dependence before elective urological oncology is increasing and is associated with adverse outcomes after surgery. There is a need to further understand the challenges associated with opioid dependence before surgery and identify and optimize these patients to improve outcomes.

A novel prognostic model predicting overall survival in patients with metastatic castration-resistant prostate cancer receiving standard chemotherapy: A multi-trial cohort analysis.

PURPOSE: Generalizable, updated, and easy-to-use prognostic models for patients with metastatic castration-resistant prostate cancer (mCRPC) are lacking. We developed a nomogram predicting the overall survival (OS) of mCRPC patients receiving standard chemotherapy using data from five randomized clinical trials (RCTs). METHODS: Patients enrolled in the control arm of five RCTs (ASCENT 2, VENICE, CELGENE/MAINSAIL, ENTHUSE 14, and ENTHUSE 33) were randomly split between training (n = 1636, 70%) and validation cohorts (n = 700, 30%). In the training cohort, Cox regression tested the prognostic significance of all available variables as a predictor of OS. Independent predictors of OS on multivariable analysis were used to construct a novel multivariable model (nomogram). The accuracy of this model was tested in the validation cohort using time-dependent area under the curve (tAUC) and calibration curves. RESULTS: Most of the patients were aged 65-74 years (44.5%) and the median (interquartile range) follow-up time was 13.9 (8.9-20.2) months. At multivariable analysis, the following were independent predictors of OS in mCRPC patients: sites of metastasis (visceral vs. bone metastasis, hazard ratio [HR]: 1.24), prostate-specific antigen (HR: 1.00), aspartate transaminase (HR: 1.01), alkaline phosphatase (HR: 1.00), body mass index (HR: 0.97), and hemoglobin (≥13 g/dl vs. <11 g/dl, HR: 0.41; all p < 0.05). A nomogram based on these variables was developed and showed favorable discrimination (tAUC at 12 and 24 months: 73% and 72%, respectively) and calibration characteristics on external validation. CONCLUSION: A new prognostic model to predict OS of patients with mCRPC undergoing first line chemotherapy was developed. This can help urologists/oncologists in counseling patients and might be useful to better stratify patients for future clinical trials.

Metabolic syndrome and bladder cancer.

Metabolic syndrome (MetS) is a widely diffused dysmetabolism, well known to be associated with an increased cardiovascular risk. However, a growing burden of evidence links MetS with several malignancies, potentially influencing the onset, progression, and therapeutic response. In this work, we critically explored the relationship between MetS and bladder cancer through a narrative review, researching the most recent literature on the topic using PubMed, MEDLINE, and EMBASE. We found that the current evidence on the subject is heterogeneous and inconsistent, making it difficult to draw definitive conclusions. Furthermore, since MetS would be a modifiable oncological risk factor, more high-quality data is needed for tailored treatment of bladder cancer.

Patients with renal transplant and moderate-to-severe LUTS benefit from urodynamic evaluation and early transurethral resection of the prostate.

PURPOSE: To assess long-term renal function and micturition pattern of males submitted to transurethral resection of the prostate (TURP) for moderate-to-severe lower urinary tract symptoms (LUTS) after renal transplantation (RT). To investigate the role of clinical and urodynamic (UD) parameters for bladder outlet obstruction (BOO) diagnosis in these patients. METHODS: Retrospective data analysis of ≥ 50 years old patients who underwent RT between 01/2005 and 12/2016. Patients with moderate-to-severe LUTS after RT who underwent a urologic evaluation and a UD study were included. TURP was performed in case of BOO diagnosis. Kidney function and micturition patterns were evaluated before, 3, 12, 24, 36, and 48 months after TURP. Predictors of BOO were assessed at univariable and multivariable logistic regression models. Statistical analysis was performed with STATA16. RESULTS: 233 male patients ≥ 50 years underwent RT. 71/233 (30%) patients developed voiding LUTS. 52/71 (73%) patients with moderate-to-severe LUTS underwent UD. TURP was performed in 36/52 (69%) patients, with BOO diagnosis. Median (interquartile range) follow-up was 108 (75-136) months. Maximum flow at flowmetry (Qmax), International Prostate Symptom Score and post-voided residual volume improved significantly after surgery. Serum creatinine decreased and glomerular filtration rate improved significantly at follow-up, especially when TURP was performed ≤ 6 months from RT. At the multivariable model, bladder capacity ≥ 300 mL (OR = 1.74, CI 95% 1.03-3.15, p = 0.043) and detrusor pressure at Qmax (OR = 2.05, CI 95% 1.48-3.02, p = 0.035) were the independent predictors of BOO. CONCLUSION: RT patients with moderate-to-severe LUTS at risk for BOO and graft failure are better identified by UD than clinical parameters. Bladder capacity and voiding pressure are key for the early diagnosis of BOO.

The combination of waterjet ablation (Aquabeam®) and holmium laser power for treatment of symptomatic benign prostatic hyperplasia: early functional results.

INTRODUCTION: The aim of this study was to assess the short-term functional outcomes and the efficacy of hemostasis performed with holmium laser performed following prostatic hydroablation with the Aquabeam® system. MATERIAL AND METHODS: Between June 2019 and July 2020, 53 consecutive patients underwent Aquabeam® with our modified hemostasis approach with holmium laser. The following standard preoperative assessments were retrospectively recorded: prostate volume; International Prostate Symptom Score (IPSS) and Quality of Life (IPSS-QoL); uroflowmetry including Qmax and post void residual volume (PVR). RESULTS: Fifty-three patients consecutively underwent aquablation and holmium laser hemostasis. Median age at surgery, median prostate-specific antigen (PSA) and median prostate volume were 62 years (IQR: 57-66), 2.95 ng/ml (IQR: 1.6-4.8) and 55 ml (IQR: 43-65), respectively.Median operative time was 60 minutes (IQR: 40-80). Median catheterization time and length of hospital stay were 2 days (IQR: 1-3) for both parameters. The median hemoglobin decrease between the preoperative values and those assessed on the second day was equal to 1.25 g/dl (IQR: 0.7-1.85).Continence rate was 100% at catheter removal. Thirty-six patients (72%) reported anterograde ejaculation preservation. IPSS (6, 3-21) and Qmax (19, 9-26) changed dramatically between baseline and 3 months follow-up. CONCLUSIONS: The combination of Aquabeam® and holmium laser energy for hemostasis is a safe, reproducible technique to relieve moderate lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) while preserving ejaculation in younger and sexually active individuals. The short-term results showed a lower rate of complications; the encouraging functional results confirm that this can be a valid surgical approach for treatment of BPH.

Renal Tumor Size and Presence of Synchronous Lung Metastasis at Time of Diagnosis: Implications for Chest Imaging.

OBJECTIVE: To quantify synchronous lung metastasis risk based on renal tumor size and determine a renal tumor size threshold to determine when chest imaging is warranted. METHODS: We assessed 253,838 patients diagnosed with a renal tumor who underwent staging chest imaging between 2010 and 2016 within the National Cancer Database. Patients were stratified by renal tumor size in 10 mm increments, and synchronous lung metastasis risk was calculated for each category. Logistic regression analyses were used to test the relationship between renal tumor size and presence of synchronous lung metastasis after adjusting to all available covariables. RESULTS: Overall, 14,524 out of 253,838 (5.7%) patients had evidence of synchronous lung metastasis. Median (IQR) tumor size for patients with vs without sLM was 90 mm (65-115) vs 40 mm (25-60), respectively. The incidence of synchronous lung metastasis was low for renal tumors <40 mm, without significant change, based on tumor size. Conversely, synchronous lung metastasis increased proportionally to renal tumor size for lesions ≥40 mm. In our cohort, 47% of patients (120,386/253,838) had a renal tumor <40 mm, and 0.9% (1,135/120,386) of these had patients had synchronous lung metastasis. Only 8% (1,135/14,524) of patients with synchronous lung metastasis had a renal tumor <40 mm. CONCLUSION: The risk of synchronous lung metastasis increased proportionally to renal tumor size; however, the risk was low for tumors <40 mm. These findings suggest that there may be minimal utility of performing screening chest imaging for patients with renal tumors <40 mm.

Impact of Lymphovascular Invasion on Overall Survival in Patients With Prostate Cancer Following Radical Prostatectomy: Stage-per-Stage Analysis.

BACKGROUND: The detrimental impact of lymphovascular invasion (LVI) in prostate cancer (PCa) on biochemical recurrence has been described; the impact of LVI on overall survival (OS) remains unclear. This investigation sought to evaluate the impact of LVI on OS in patients with PCa. METHODS: We examined men with nonmetastatic PCa treated with radical prostatectomy between 2010 and 2015. Only men with documented LVI status were included (n = 232,704). Patients were stratified according to final pathologic T stage (pT2, pT3a, and pT3b). RESULTS: Of the 232,704 patients who met inclusion criteria, 17,758 (8%) were found to have LVI on final pathology. Overall, 174,838 (75%), 40,281 (17%), and 17,585 (8%) patients had pT2, pT3a, and pT3b disease, respectively. Median follow-up was 42.7 months (27.1-58.7). At 5 years, the OS in LVI versus non-LVI patients was 94% versus 95% in pT2 (P = .0004), 92% versus 95% in pT3a (P < .0001), and 86% versus 92% in pT3b (P < .0001). On multivariable analysis, LVI status was not an independent predictor of OS in pT2 disease (hazard ratio, 1.12; 95% confidence interval [CI], 0.93-1.36; P = .2). In pT3a and pT3b disease, presence of LVI had 1.2-fold (95% CI, 1.03-1.44; P = .02) and 1.4-fold (95% CI, 1.20-1.59; P < .001) higher overall mortality than their counterparts without LVI. CONCLUSIONS: Our report demonstrates the detrimental impact of LVI on OS in locally advanced PCa (pT3a and higher). This information may prove valuable when risk stratifying based on final pathology.

Nomograms in Urologic Oncology: Lights and Shadows.

Decision-making in urologic oncology involves integrating multiple clinical data to provide an answer to the needs of a single patient. Although the practice of medicine has always been an "art" involving experience, clinical data, scientific evidence and judgment, the creation of specialties and subspecialties has multiplied the challenges faced every day by physicians. In the last decades, with the field of urologic oncology becoming more and more complex, there has been a rise in tools capable of compounding several pieces of information and supporting clinical judgment and experience when approaching a difficult decision. The vast majority of these tools provide a risk of a certain event based on various information integrated in a mathematical model. Specifically, most decision-making tools in the field of urologic focus on the preoperative or postoperative phase and provide a prognostic or predictive risk assessment based on the available clinical and pathological data. More recently, imaging and genomic features started to be incorporated in these models in order to improve their accuracy. Genomic classifiers, look-up tables, regression trees, risk-stratification tools and nomograms are all examples of this effort. Nomograms are by far the most frequently used in clinical practice, but are also among the most controversial of these tools. This critical, narrative review will focus on the use, diffusion and limitations of nomograms in the field of urologic oncology.

Impact of high-intensity local treatment on overall survival in stage IV upper tract urothelial carcinoma.

OBJECTIVES: To investigate the impact of high-intensity local treatment (LT) on overall survival (OS) in patients with stage IV upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Within the National Cancer Database, we identified 7,357 patients diagnosed with stage IV UTUC from 2004 to 2015. Patients who underwent high-intensity LT, defined as radical surgery of the primary tumor, were compared with those who did not. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Weighted survival analyses were used to test the association between high-intensity LT and OS. Multivariable Cox model was used to assess for independent predictors of OS. Sensitivity analysis was used to account for possible biases. RESULTS: Among stage IV patients, 10.6% (n = 779) had locally advanced disease (T4), 32.6% (n = 2,399) had node-positive disease (N+) and 56.8% (N = 4,179) had distant metastases (M+). Fewer than half of the patients underwent high-intensity LT (n = 2,908, 39.5%) while the remainder did not. On IPTW-adjusted survival analysis, high-intensity LT was associated with a prolonged OS (11.17 months [IQR, 5.19 to 24.28] months vs. 6.18 months [IQR, 2.27 to 14.49], P ≤ 0.001). A similar benefit was seen on adjusted survival analyses for each stage IV subgroup, defined according to TNM characteristics. The survival benefit was confirmed at sensitivity analysis. CONCLUSION: High-intensity LT in balanced cohorts of patients with stage IV UTUC is associated with prolonged OS including those with locally advanced (T4), node-positive (N+) or distant metastases (M+).

Evaluation of lymphovascular invasion as a prognostic predictor of overall survival after radical prostatectomy.

OBJECTIVE: To assess the prognostic ability of lymphovascular invasion (LVI) as a predictor of overall survival (OS). MATERIALS AND METHODS: We included 126,682 prostate cancer (CaP) cM0 patients who underwent radical prostatectomy with lymph node dissection between 2010 and 2015, within the National Cancer Database. Patients who received androgen deprivation therapy were included. Patients were divided into four sub-cohorts based on LVI and lymph node invasion (LNI) status: pL0N0, pL1N0, pL0N1, and pL1N1. Kaplan-Meier curves estimated OS and Cox-regression analysis tested the relationship between LVI and OS. RESULTS: Median (IQR) age and PSA at diagnosis were 62 (57-66) years and 5.7 (4.5-8.9) ng/ml, respectively. Most patients had pT2 stage (68.5%), and pathological Gleason 3+4 (46.7%). 10.0% and 4.0% patients had LVI and LNI, respectively. Median follow-up was 42 months (27-58). At 5-years, OS was 96.5% in pL0N0 patients vs 93.1% pL1N0 patients vs 93.3% in pL0N1 patients vs 86.6% pL1N1 patients. LVI was an independent predictor of OS (hazard ratio [HR]:1.28). LVI showed interaction with LNI, as LVI was associated with a higher overall-mortality in patients with LNI (HR:1.66), than in patients without LNI (HR:1.22). (all P<0.0001) CONCLUSIONS: Our report highlights the detrimental impact of LVI on OS. Patients with LVI alone fared similarly to patients with LNI alone. Patients with both LVI and LNI had worse OS than those with only LVI or LNI, implying a synergetic detrimental interaction. Our findings demonstrate an important utility that LVI can provide in deciding patients' prognoses.

Successful Treatment of Vesicovaginal Fistulas via an Abdominal Transvesical Approach: A Single-center 50-yr Experience.

BACKGROUND: A vesicovaginal fistula (VVF) is an abnormal communication between bladder and vagina, as a result of traumatic events to the female pelvis. A VVF is a rare event and challenging to cure. Successful treatment can be achieved through an abdominal approach, especially in complex or recurrent cases. This approach has been used in our institution as the procedure of choice for the past 50yr. OBJECTIVE: To analyze the results of the management of VVFs in our institution and to highlight the key points for success. DESIGN, SETTING, AND PARTICIPANTS: A total of 138 patients with VVFs have been treated in our institution between 1969 and 2019. Up to now, this is the largest series reported so far on abdominal treatment of VVFs in the developed world. INTERVENTION: an abdominal transvesical approach has been performed as the procedure of choice. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: to evaluate the factors influencing the success rate of the abdominal approach at the first closure attempt. Statistical analysis was performed using STATA software. RESULTS AND LIMITATIONS: In total, 124 (90%) patients were submitted to transabdominal repair (89 extraperitoneal; 71.8%), 113 (91.1%) presented with a VVF not associated with another fistula, and 36 (29.0%) had undergone previous unsuccessful treatments elsewhere. Successful closure was obtained in 111/118 (94.1%) patients at the first attempt, excluding external noncontinent urinary diversions. Follow-up was possible in 95 (76.6%) patients; 91 (95.8%) patients were dry. Statistical analysis showed a significant association between fistula size and length, and VVF site in the bladder and extraperitoneal approach. Success rate decreased with the number of previous attempts and did not vary with VVF etiology. CONCLUSIONS: The abdominal approach for the treatment of VVF has a high success rate. Standardization of the technique, identification of surgical key points, and centralization of care in centers with experience are critical. PATIENT SUMMARY: A vesicovaginal fistula (VVF) is a rare clinical condition, with a high impact on patients' quality of life. We report a large series of VVFs treated in our institution in the past 50yr. Key factors for success include proper surgical technique and centralization of care in centers with high experience.

Development of a Surgical Safety Training Program and Checklist for Conversion during Robotic Partial Nephrectomies.

OBJECTIVE: To evaluate the impact of standardized training and institutional checklists on improving teamwork during complications requiring open conversion from robotic-assisted partial nephrectomy (RAPN). MATERIALS AND METHODS: Participants to a surgical team safety training program were randomly divided into 2 groups. A total of 20 emergencies were simulated: group 1 performed simulations followed by a 4-hour theoretical training; group 2 underwent 4-hour training first and then performed simulations. All simulations were recorded and scored by 2 independent physicians. Time to conversion (TC) and procedural errors were analyzed and compared between the 2 groups. A correlation analysis between the number of previous conversion simulations, total errors number, and TC was performed for each group. RESULTS: Group 1 showed a higher TC than group 2 (116.5 vs 86.5 seconds, P = .0.53). As the number of simulation increased, the numbers of errors declined in both groups. The 2 groups tend to converge toward 0 errors after 9 simulations; however, the linear correlation was more pronounced in group 1 (R2 = 0.75). TC shows a progressive decline for both groups as the number of simulations increases (group 1, R2 = 0.7 and group 2, R2 = 0.61), but it remains higher for group 1. Lack of task sequence and accidental falls or loss of sterility were higher in group 1. CONCLUSION: OC is a rare but potentially dramatic event in the setting of RAPN, and every robotic team should be prepared to manage intraoperative emergencies. Training protocols can effectively improve teamwork and facilitate timely conversions to open surgery in the event of intraoperative emergencies during RAPN. Further studies are needed to confirm if such protocols may translate into an actual safety improvement in clinical settings.