Experimental and New Approaches for Bladder Preservation in Intermediate and High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC).

About 75% of bladder cancers are detected as non-muscle invasive. High-risk patients have high progression risk. Although the standard is transurethral resection of bladder tumor plus full dose intravesical BCG for one to 3 years, due to the high risk of progression, radical cystectomy may be considered in specific cases. Although radical cystectomy is still the best approach for high-grade NMIBC from an oncological perspective, its high morbidity and impact on quality of life motivate studies of new strategies that may reduce the need for cystectomy. We carried out a mini-review whose objectives were: 1 - to identify bladder-sparing alternatives that are being studied as possible treatment for patients with intermediate and high-risk NMIBC; 2 - understand the evidence that exists regarding success rate, follow-up, and side effects of different strategies. Several studies have sought alternatives for bladder preservation, including immunotherapy, intravesical chemotherapy, chemo-hyperthermia, antibody-drug conjugates, viral genetic therapy, and others with promising results. The selection of an optimal therapy for high-risk NMIBC that can reduce the need for cystectomy, with low toxicity and high efficacy, is of paramount importance and remains an issue, however, several known medications are being tested as bladder-preserving alternatives in this scenario and have shown promise in studies.

Smoking characteristics and years since quitting smoking of US adults diagnosed with lung and bladder cancer: A national health and nutrition examination survey analysis.

PURPOSE: Smoking is a recognized risk factor for bladder BC and lung cancer LC. We investigated the enduring risk of BC after smoking cessation using U.S. national survey data. Our analysis focused on comparing characteristics of LC and BC patients, emphasizing smoking status and the latency period from smoking cessation to cancer diagnosis in former smokers. MATERIALS AND METHODS: We analyzed data from the National Health and Examination Survey (2003-2016), identifying adults with LC or BC history. Smoking status (never, active, former) and the interval between quitting smoking and cancer diagnosis for former smokers were assessed. We reported descriptive statistics using frequencies and percentages for categorical variables and median with interquartile ranges (IQR) for continuous variables. RESULTS: Among LC patients, 8.9% never smoked, 18.9% active smokers, and 72.2% former smokers. Former smokers had a median interval of 8 years (IQR 2-12) between quitting and LC diagnosis, with 88.3% quitting within 0-19 years before diagnosis. For BC patients, 26.8% never smoked, 22.4% were active smokers, and 50.8% former smokers. Former smokers had a median interval of 21 years (IQR 14-33) between quitting and BC diagnosis, with 49.3% quitting within 0-19 years before diagnosis. CONCLUSIONS: BC patients exhibit a prolonged latency period between smoking cessation and cancer diagnosis compared to LC patients. Despite smoking status evaluation in microhematuria, current risk stratification models for urothelial cancer do not incorporate it. Our findings emphasize the significance of long-term post-smoking cessation surveillance and advocate for integrating smoking history into future risk stratification guidelines.

Exploring preventive care practices among unvaccinated individuals in the United States during the COVID-19 pandemic.

INTRODUCTION: Building on a Canadian study associating unvaccinated individuals to increased car accidents, we examined the relationship between COVID-19 vaccination status and US preventive care practices. METHODS: We queried the 2021 National Health Interview Survey. First, we fitted a model to identify respondent-level factors associated with receipt of at least one COVID-19 vaccination. Second, we fitted a survey-weighted logistic regression model adjusted for respondent-level characteristics to examine whether the receipt of at least one COVID-19 vaccination predicted the receipt of preventive care services. Preventive care services assessed included serum cholesterol, glucose, and blood pressure measurements, as well as guideline-concordant cancer screening including breast, cervical, colorectal, and prostate cancer screening. RESULTS: Factors predicting receipt of COVID-19 vaccination were age (adjusted Odds Ratio (aOR) 1.03; 95 % confidence interval (CI) [1.03-1.03]), Hispanic (aOR 1.25; 95 % CI [1.08-1.44]), and non-Hispanic Asian (aOR 3.52; 95 % CI [2.74-4.52]) ethnicity/race, and history of cancer (aOR 1.61; 95 % CI [1.13-2.30]). Unvaccinated respondents were less likely to have received serum cholesterol (aOR 0.69; 95 % CI [0.50-0.70), serum glucose (aOR 0.65; 95 % CI [0.56-0.75]), or blood pressure measurements (aOR 0.47; 95 % CI [0.33-0.66]); and were less likely to have received breast cancer (aOR 0.35; 95 % CI [0.25-0.48]), colorectal cancer (aOR 0.52; 95 % CI [0.46-0.60]) and prostate cancer screening (aOR 0.61; 95 % CI [0.48-0.76]). There was no significant association between unvaccinated respondents receiving cervical cancer screening (aOR 0.96; 95 % CI [0.81-1.13]; p = 0.616). CONCLUSION: Non-receipt of COVID-19 vaccination was associated with non-receipt of preventive care services including cancer screening. Further studies are needed to assess if this association is due to system-level factors or reflects a general distrust of medical preventive care amongst this population.

Urinary miRNAs Predict Metastasis in Patients With Clinically Localized Clear Cell Renal Cell Carcinoma Treated With Nephrectomy.

PURPOSE: Patients with clear cell renal cell carcinoma (ccRCC) might develop metastasis after surgery with curative intent. We aimed to characterize the expression levels of microRNAs in the urine (UmiRNAs) of patients before and after nephrectomy to determine the impact of UmiRNAs expression in the emergence of metastases. METHODS: We prospectively collected pre- and post-nephrectomy urine samples from 117 patients with clinically localized and locally advanced ccRCC. UmiRNAs were extracted, purified, and measured using RT-PCR. Relative quantifications (RQ) of 137 UmiRNAs were calculated through 2-∆∆ method. The post-surgery/pre-surgery RQs ratio represented the magnitude of the expression levels of the UmiRNAs. The association of UmiRNA expression and the development of distant metastases was tested with Cox regression model. RESULTS: Five UmiRNAs (miR-191-5p, miR-324-3p, miR-186-5p, miR-93-5p, miR-30b-5p) levels were upregulated before nephrectomy (p < .05). This conferred a 2- to 4-fold increased risk of metastasis, with miR-191-5p showing the most significant association with this endpoint (HR = 4.16, 95% CI = 1.38-12.58, p = .011). In a multivariate model stratified with stage and Fuhrman grade, we found that miR-191-5p, miR-324-3p, and miR-186-5p exhibited a strong association with metastasis development in patients with pathological T3 (pT3) tumors. Enrichment analysis with the most differentially expressed UmiRNAs showed that these UmiRNAs targeted genes that regulate cell survival and proliferation. CONCLUSION: Our study indicated UmiR-191-5p, UmiR-324-3p, and UmiR-186-5p are potential markers to predict the development of metastasis, particularly in pT3 patients. PATIENT SUMMARY: We compared changes of UmiRNAs expression detected pre- and postnephrectomy of patients with ccRCC. Our findings suggest that UmiRNA expression likely reflects tumor-specific changes that can be promising to predict the metastasis development, particularly in patients with non-metastatic locally advanced ccRCC. If confirmed, these findings may be useful for surveillance protocols for adjuvant therapy protocols.

Long-term oncological and surgical outcomes after Video Endoscopic Inguinal Lymphadenectomy (VEIL) in patients with penile cancer

ABSTRACT Objective: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). Materials and Methods: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. Results: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. Conclusion: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.

Continence criteria of 193 618 patients after open, laparoscopic, and robot-assisted radical prostatectomy.

OBJECTIVES: To apply a new evidence-gathering methodology, called reverse systematic review (RSR), to analyse the influence of different continence classification criteria on urinary continence rates among open retropubic radical prostatectomy (RRP), laparoscopic RP (LRP) and robot-assisted RP (RARP). MATERIALS AND METHODS: A search was carried out in eight databases between 2000 and 2020 through systematic reviews (SRs) studies referring to RRP, LRP or RARP (80 SRs). All references used in these SRs were captured referring to 910 papers in an overall database called the 'EVIDENCE Database'. A total of 422 studies related to post-RP urinary continence were selected for the final analysis, totalling 782 reports referring to 193 618 patients. RESULTS: Overall, 206 (26.4%) reports for RRP, 243 (31.0%) reports for LRP, and 333 (42.6%) reports for RARP were found. Mean overall continence rates, respectively for RRP, LRP and RARP, were: 42%, 34% and 42% at 1 month; 62%, 64% and 65% at 3 months; 73, 77 and 79% at 6 months; and 81%, 85% and 86% at 12 months. The most used criterion was 'No pad' (53.3%), followed by 'Safety pad' (19.3%), 'Not described' (10.6%), and 'No leak' (9.9%). 'No pad' showed the lowest discrepancy in continence rates in each period compared to the overall average for each technique, demonstrating less ability to influence the final results favouring any of the techniques. CONCLUSION: The RSR demonstrated that the 'No pad' criterion was the most used in the literature and showed the lowest bias capable of influencing the results and favouring any of the techniques and is the fairest option for future comparisons.

Healthcare Workers (HCWs) and non-HCWs reaction to Bacillus Calmette-Guérin (BCG) in the BATTLE trial.

OBJECTIVES: Healthcare workers (HCWs) may have different response to Bacillus Calmette-Guérin (BCG) vaccination due to previous occupational exposure to Mycobacterium particles. We report subgroup analysis of the BATTLE trial, comparing BCG effects in HCWs vs non-HCWs. This was a secondary analysis of a trial. METHODS: The BATTLE trial was a double-blind placebo-controlled phase III clinical trial that investigated BCG revaccinating adults who were recently infected with SARS-CoV-2 virus. BCG and placebo recipients were sub-grouped based on regular occupational contact with patients into HCWs (48 BCG and 50 placebo) and non-HCWs (124 BCG and 134 placebo). Weekly COVID-19 symptom progression and injection site reactions were compared between subgroups on weeks one, two, three, and six follow-ups. RESULTS: HCWs were more likely to complain of itching on the injection site early after injection (OR = 2.5, p = 0.049). They developed peeling and crusting on the site of injection faster than non-HCWs (during the second week, p = 0.033 and 0.040, OR = 3.3 and 2.7, respectively). HCWs were also more likely to maintain their papule or develop a late onset pustule during later weeks (weeks four and six, p = 0.024 and 0.006, OR = 2.2 and 8.6, respectively). In terms of COVID-19 symptom progression, recovery from anosmia was more likely in the non-HCWs who received BCG (week six, pHolm's corrected = 0.002, OR = 3.3). CONCLUSION: HCWs' local reaction to BCG injection was slightly more rapid and more intense, possibly due to their occupational exposure. BCG may also ameliorate COVID-19 induced inflammation and anosmia in non-HCWs but not HCWs. Therefore, HCWs might be less likely to benefit from BCG vaccination. CLINICALTRIALS: gov register number NCT04369794.

Uncovering the Changing Treatment Landscape for Low-risk Prostate Cancer in the USA from 2010 to 2020: Insights from the National Cancer Data Base.

The management of prostate cancer (PCa) has evolved from a paradigm of "treat when caught early" to "treat only when necessary". Despite inconsistency in its use, active surveillance has evolved over the past two decades into the gold standard for management of low-risk PCa. Our objective was to investigate whether the use of expectant management (active surveillance, watchful waiting, no treatment) as a first-line approach for low-risk PCa has increased over the past decade. We queried the US National Cancer Data Base for men diagnosed with localized PCa between 2010 and 2020. Two multivariable logistic regression models with different two-way interaction terms (year of diagnosis × D'Amico risk classification, and year of diagnosis × International Society of Urological Pathology [ISUP] grade group) were fitted to predict the probability of undergoing expectant management versus active treatment. The predicted probability of expectant management increased from 13.7% in 2010 to 64.4% in 2020 for men with low-risk PCa, and from 12.9% in 2010 to 61.6% in 2020 for ISUP grade group 1 PCa (both pinteraction < 0.001). The frequency of expectant management for low-risk PCa has increased dramatically during the past decade. We expect this trend to further increase owing to the growing awareness of the harms of overtreatment of indolent disease. PATIENT SUMMARY: We examined the use of expectant management for prostate cancer between 2010 and 2020 in a large hospital-based registry from the USA. We found that the proportion of men receiving expectant management for low-risk prostate cancer is increasing. We conclude that growing awareness of the harms of overtreatment has profoundly affected trends for prostate cancer treatment in the USA.

Bladder cancer immunomodulatory effects of intravesical Nitazoxanide, Rapamycin, Thalidomide and Bacillus Calmette-Guérin (BCG).

PURPOSE: To understand the effect of Nitazoxanide (NTZ), Rapamycin, Thalidomide, alone and in combination with BCG on bladder cancer (BC) histopathology and programmed death-ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) expression. METHODS: Female Fisher-344 rats underwent intravesical N-methyl-N-nitrosourea (MNU) followed by weekly intravesical treatment with saline (controls, n = 10), BCG (n = 10), NTZ (n = 8), BCG plus NTZ (n = 8), Rapamycin (n = 10) BCG plus Rapamycin (n = 10), Thalidomide (n = 10), and BCG plus Thalidomide (n = 10), and euthanized after 8 weeks and their bladders were investigated for BC and PD-L1 and CTLA4 expression. RESULTS: Rapamicyn alone and in combination with BCG had the lowest number of bladder neoplasias in the histopathology exam (1/10). Neoplastic lesions were found in 4/10 BCG recipients, 5/10 Thalidomide recipients, 4/10 Thalidomide plus BCG recipients, 5/8 NTZ and 3/8 NTZ plus BCG recipients. Adding NTZ to BCG increased the expression of PD-L1 and adding Rapamycin or Thalidomide decreased PD-L1 and CTLA4 expression compared to BCG alone. Rapamycin alone significantly increased CTLA4 and slightly increased PD-L1 expression but its combination with BCG significantly decreased both markers. Thalidomide had a similar effect; however, it was only slightly different from the control and BCG alone groups. CONCLUSION: Intravesical BCG combination treatment seems to effectively prevent BC development in an immunecompetent clinically relevant animal model, introducing Thalidomide, Nitazoxanide, and specially Rapamycin as candidates in the intravesical immunotherapy advancement. Our study contributes in understanding the mechanism of cancer immunotherapy.

Long-term oncological and surgical outcomes after Video Endoscopic Inguinal Lymphadenectomy (VEIL) in patients with penile cancer.

OBJECTIVE: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). MATERIALS AND METHODS: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. RESULTS: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. CONCLUSION: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.

The Risk of Catastrophic Healthcare Expenditures Among Prostate and Bladder Cancer Survivors in the United States.

INTRODUCTION: Little is known about the rates of catastrophic health care expenditures among survivors of prostate and bladder cancer or the factors that place patients at highest risk for undue cost. MATERIALS AND METHODS: The Medical Expenditure Panel Survey was utilized to identify prostate and bladder cancer survivors from 2011 to 2019. Rates of catastrophic health care expenditures (out-of-pocket health care spending >10% household income) were compared between cancer survivors and adults without cancer. A multivariable regression model was used to identify risk factors for catastrophic expenditures. RESULTS: Among 2620 urologic cancer survivors, representative of 3,251,500 (95% CI 3,062,305-3,449,547) patients annually after application of survey weights, there were no significant differences in catastrophic expenditures among respondents with prostate cancer compared to adults without cancer. Respondents with bladder cancer had significantly greater rates of catastrophic expenditures (12.75%, 95% CI 9.36%-17.14% vs. 8.33%, 95% CI 7.66%-9.05%, P = .027). Significant predictors of catastrophic expenditures in bladder cancer survivors included older age, comorbidities, lower income, retirement, poor health status, and private insurance. Though White respondents with bladder cancer had no significantly increased risk of catastrophic expenditures, among Black respondents the risk of catastrophic expenditures increased from 5.14% (95% CI 3.95-6.33) without bladder cancer to 19.49% (95% CI 0.84-38.14) with bladder cancer (OR 6.41, 95% CI 1.28-32.01, P = .024). CONCLUSIONS: Though limited by small sample size, these data suggest that bladder cancer survivorship is associated with catastrophic health care expenditures, particularly among Black cancer survivors. These findings should be taken as hypothesis-generating and warrant further investigation with larger sample sizes and, ideally, prospective investigation.

The Use of Chatbots in Oncological Care: A Narrative Review.

Background: Few reports have investigated chatbots in patient care. We aimed to assess the current applications, limitations, and challenges in the literature on chatbots employed in oncological care. Methods: We queried the PubMed database through April 2022 and included studies that investigated the use of chatbots in different phases of oncological care. The search used five different combinations of the specific terms "chatbot", "cancer", "oncology", and "conversational agent". Inclusion criteria were chatbot use in any aspect of oncological care-prevention, patient education, treatment, and surveillance. Results: The initial search yielded 196 records, 21 of which met inclusion criteria. The identified chatbots mostly focused on breast and ovarian cancer (n=8), with the second most common being cervical cancer (n=3). Good patient satisfaction was reported among 14 of 21 chatbots. The most reported chatbot applications were cancer screening, prevention, risk stratification, treatment, monitoring, and management. Of 12 studies examining efficacy of care via chatbot, 9 demonstrated improvements compared to standard care. Conclusion: Chatbots used for oncological care to date demonstrate high user satisfaction, and many have shown efficacy in improving patient-centered communication, accessibility to cancer-related information, and access to care. Currently, chatbots are primarily limited by the need for extensive user-testing and iterative improvement before widespread implementation.

Radical Prostatectomy Technique Dispute: Analyzing Over 1.35 Million Surgeries in 20 Years of History.

Systematic reviews (SR) produce the best evidence comparing open (RRP), laparoscopic (LRP), and robotic (RARP) radical prostatectomy (RP). However, the hyperfiltration of evidence generates very specific scenarios that reduce the power of extrapolation. To compare RP evidence regarding demographics using a new methodology called reverse systematic review (RSR). Between 2000 and 2020, 8 databases were searched for SR studies on RRP, LRP, or RARP. All references were captured and analyzed over time in 80 SR. Total of 1724 reports (nr = 752, 43.7% for RARP; nr = 559, 32.4% for RRP; nr = 413, 23.9% for LRP) described 1,353,485 patients (881,719, 65.1% RRP; 366,006, 27.0% RARP; 105,760, 7.8% LRP). Patients/center/year was higher in RARP compared to LRP and RRP, median 50.0, 40.0, and 36.66, respectively, P < .001. Surgeons per study was lesser in RARP and LRP compared to RRP, median 2.0, 2.0, and 6.0, respectively, P < .001. Study duration and follow-up in years was shorter in RARP compared to LRP and RRP, median 2.6, 3.0, and 4.0, respectively, P < .001. Cumulative RARP reports predominate in North America (55.7%, nr = 468) and Asia (47.8%, nr =129), while LRP predominate in Europe (42.3%, nr =230) and RRP in Oceania (45.1%, nr = 23). After 2010 all continents began to accumulate more patients in the robotic approach. Potential biases related to shorter follow-up, greater volume centers, and surgeons were identified favoring the RARP. Analyzing the context of the available evidence is essential to compare techniques. Influenced by economic and scientific interests, robotic surgery was developed in centers with a higher volume of surgeries, characterizing potential biases when comparing techniques in the clinical shared decision.