Smoking is not associated with wound complications in augmented urethroplasty: a NSQIP analysis.

OBJECTIVE: To investigate if predictors of wound complications differed between patients undergoing excision and primary anastomosis urethroplasty (EPA) and augmented urethroplasty. METHODS: The National Surgical Quality Improvement Program database from 2006 to 2018 was queried for male patients undergoing urethroplasty. Thirty-day wound complications were identified and categorized (superficial/deep/organ-space surgical site infections and dehiscence). Multivariable logistic regression was performed to determine risk factors associated with wound complications. Smoking history was defined as current smoker within the past year. RESULTS: Urethroplasty was performed in 2251 males, with 25.46% (n = 573) using a flap or graft. There was no significant difference in wound complications for patients undergoing augmented urethroplasty (n = 17, 2.97%) or EPA (n = 45, 2.68%) (p = 0.9). The augmented group had a higher BMI, longer operative time, and longer length of stay. On multivariable logistic regression, risk factors associated with wound complications for patients undergoing EPA were diabetes (OR 2.56, p = 0.03) and smoking (OR 2.32, p = 0.02). However, these factors were not associated with wound complications in patients undergoing augmented urethroplasty. CONCLUSIONS: Smoking and diabetes were associated with increased wound complications for men undergoing EPA, but not in patients undergoing augmented urethroplasty. Patients with comorbidities associated with worse wound healing may be more likely to have a wound complication when undergoing EPA.

Optimal management of radiation pneumonitis: Findings of an international Delphi consensus study.

PURPOSE: Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study. METHODS: In Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3. RESULTS: Response rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease. CONCLUSIONS: This Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP.

Tumour growth rate predicts overall survival in patients with recurrent WHO grade 4 glioma.

PURPOSE: Accurate prognostication may aid in the selection of patients who will benefit from surgery at recurrent WHO grade 4 glioma. This study aimed to evaluate the role of serial tumour volumetric measurements for prognostication at first tumour recurrence. METHODS: We retrospectively analyzed patients with histologically-diagnosed WHO grade 4 glioma at initial and at first tumour recurrence at a tertiary hospital between May 2000 and September 2018. We performed auto-segmentation using ITK-SNAP software, followed by manual adjustment to measure serial contrast-enhanced T1W (CE-T1W) and T2W lesional volume changes on all MRI images performed between initial resection and repeat surgery. RESULTS: Thirty patients met inclusion criteria; the median overall survival using Kaplan-Meier analysis from second surgery was 10.5 months. Seventeen (56.7%) patients received treatment post second surgery. Univariate cox regression analysis showed that greater rate of increase in lesional volume on CE-T1W (HR = 2.57; 95% CI [1.18, 5.57]; p = 0.02) in the last 2 MRI scans leading up to the second surgery was associated with a higher mortality likelihood. Patients with higher Karnofsky Performance Score (KPS) (HR = 0.97; 95% CI [0.95, 0.99]; p = 0.01) and who received further treatment following second surgery (HR = 0.43; 95% CI [0.19, 0.98]; p = 0.04) were shown to have a better survival. CONCLUSION: Higher rate of CE-T1W lesional growth on the last 2 MRI images prior to surgery at recurrence was associated with increase mortality risk. A larger prospective study is required to determine and validate the threshold to distinguish rapidly progressive tumour with poor prognosis.

Oncogene-Driven Non-Small Cell Lung Cancers in Patients with a History of Smoking Lack Smoking-Induced Mutations.

Non-small cell lung cancers (NSCLC) in nonsmokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in nonsmokers, alterations in these "nonsmoking-related oncogenes" (NSRO) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared with typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and nonsmokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC data sets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to the regulation of the cell cycle. These findings suggest that, whereas the genomic landscape is similar between NSRO-driven NSCLC in smokers and nonsmokers, smoking still affects the tumor phenotype independently of genomic alterations. SIGNIFICANCE: Non-small cell lung cancers driven by nonsmoking-related oncogenes do not harbor genomic scars caused by smoking regardless of smoking history, indicating that the impact of smoking on these tumors is mainly nongenomic.

Reproductive factors and risk of physical frailty among Chinese women living in Singapore.

SETTING: Although age at menopause has been linked to higher risk of physical frailty in later life, little is known about other reproductive factors. OBJECTIVES: Our study aimed to investigate the associations between 1) age at menarche, 2) age at natural menopause, 3) duration of reproductive period, 4) number of children, 5) use of oral contraceptives (OCP), and 6) use of hormone replacement therapy (HRT) with the risk of physical frailty in late life. DESIGN: We used data from 5934 women of the Singapore Chinese Health Study who experienced natural menopause, and participated in the third follow-up interviews when physical frailty was assessed. Logistic regression was used to evaluate association of reproductive factors evaluated during baseline and prior follow-up interviews with physical frailty at follow-up 3. PARTICIPANTS: Community-dwelling Chinese women living in Singapore. Participants had a mean age of 52.6 years at baseline (1993-1998), and a mean age of 72.8 years during the third follow-up (2014-2017). MEASUREMENTS: Sociodemographic characteristics, level of education, smoking history, physical activity, and history of physician-diagnosed comorbidities were collected. Participants' weight and height were self-reported. We used a modified Cardiovascular Health Study phenotype to assess physical frailty. RESULTS: Age at menarche was inversely associated with the likelihood of physical frailty (Ptrend = 0.001); each one-year decrease in age at menarche was associated with a 9% increase (95% CI: 4%-14%) in odds of physical frailty. Age at menopause was also inversely associated with the likelihood of physical frailty (Ptrend = 0.009); every one-year decrease in age at menopause was associated with 2% (0%-4%) increased odds. In the assessment of frailty, younger ages at menarche and menopause were associated with greater likelihood of being in the slowest quintile for timed up-and-go and weakest quintile for handgrip strength. Conversely, duration of reproductive period, parity, and use of oral contraceptives or hormone replacement therapy were not significantly associated with the likelihood of physical frailty. CONCLUSIONS: In our population-based cohort of Chinese women, younger ages at menarche and menopause were associated with higher likelihood of physical frailty in later life.

The Association Between Duration of Antibiotics and Infectious Complications Following Radical Cystectomy: Analysis of the 2019-2021 NSQIP Database.

OBJECTIVES: To identify the impact of the duration of peri-operative antibiotics on infectious complications following radical cystectomy. METHODS: The National Surgical Quality Improvement Project (NSQIP) targeted database was queried for patients undergoing radical cystectomy from 2019 to 2021. Baseline patient characteristics were collected. Antibiotic duration was classified as <24 hours (short), 24-72 hours (intermediate) or >72 hours (long). Infectious complication data were collected including surgical site infection (SSI), urinary tract infection (UTI), organ space infection, pneumonia, sepsis, and clostridium difficile infection up to 30 days after surgery. Univariate and multivariable analyses were performed to compare duration of antibiotic therapy to infectious outcomes. RESULTS: Of the 4363 patients who underwent radical cystectomy, 3250 (74%), 827 (19%) and 286 (6.6%) received short, intermediate, and long duration of peri-operative antibiotics, respectively. Infectious complication occurred in 954 (22%) patients, including 227 (5.2%) SSI, 280 (6.4%) UTI, 268(6.1%) organ space infection, 87 (2%) pneumonia, and 378 (8.7%) sepsis. Clostridium difficile infection occurred in 89 (2%) patients. On multivariable analysis, there was no significant difference in overall infectious complication rates with long-duration antibiotics. However, intermediate duration of antibiotics in open surgery was associated with a decreased risk of SSI (OR 0.58; 95%CI 0.37-0.91) compared to those treated with short-term antibiotics. CONCLUSION: Despite guideline recommendations, 26% of patients in this database received >24 hours of peri-operative antibiotics without decreased risk of overall infectious complication. An intermediate course of antibiotics decreased risk of SSI in open surgery compared to the guideline recommend <24-hour course. Greater education regarding antibiotic stewardship and further studies investigating infectious complications are warranted.

Treatment Response Biomarkers: Working Toward Personalized Radiotherapy for Lung Cancer.

Owing to major advances in the field of radiation oncology, patients with lung cancer can now receive technically individualized radiotherapy treatments. Nevertheless, in the era of precision oncology, radiotherapy-based treatment selection needs to be improved as many patients do not benefit or are not offered optimum therapies. Cost-effective robust biomarkers can address this knowledge gap and lead to individuals being offered more bespoke treatments leading to improved outcome. This narrative review discusses some of the current achievements and challenges in the realization of personalized radiotherapy delivery in patients with lung cancer.

Precision Endpoints for Contemporary Precision Oncology Trials.

SUMMARY: Traditional endpoints such as progression-free survival and overall survival do not fully capture the pharmacologic and pharmacodynamic effects of a therapeutic intervention. Incorporating mechanism-driven biomarkers and validated surrogate proximal endpoints can provide orthogonal readouts of anti-tumor activity and delineate the relative contribution of treatment components on an individual level, highlighting the limitation of solely relying on aggregated readouts from clinical trials to facilitate go/no-go decisions for precision therapies.

Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer.

BACKGROUND: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay. METHODS: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples. RESULTS: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001). CONCLUSIONS: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting.

Comparing the rate of immunotherapy treatment change due to toxicity by sex.

BACKGROUND: Immuno-oncology therapy (IO) is associated with a variety of treatment-related toxicities. However, the impact of toxicity on the treatment discontinuation rate between males and females is unknown. We hypothesized that immune-related adverse events would lead to more frequent treatment changes in females since autoimmune diseases occur more frequently in females. AIMS: Our aim was to determine if there was a difference in the rate of immunotherapy treatment change due to toxicity between males and females. METHODS AND RESULTS: The Oncology Research Information Exchange Network Avatar Database collected clinical data from 10 United States cancer centers. Of 1035 patients receiving IO, 447 were analyzed, excluding those who did not have documentation noting if a patient changed treatment (n = 573). Fifteen patients with unknown or gender-specific cancer were excluded. All cancer types and stages were included. The primary endpoint was documented treatment change due to toxicity. Four hundred and forty-seven patients (281 males and 166 females) received IO treatment. The most common cancers treated were kidney, skin, and lung for 99, 84, and 54 patients, respectively. Females had a shorter IO course than males (median 3.7 vs. 5.1 months, respectively, p = .02). Fifty-four patients changed treatment due to toxicity. There was no significant difference between females and males on chi-square test (11.4% vs. 12.5%, respectively, p = 0.75) and multivariable logistic regression (OR 0.924, 95% CI 0.453-1.885, p = .827). Significantly more patients with chronic obstructive pulmonary disease (COPD) changed therapy due to toxicity (OR 2.491, 95% CI 1.025-6.054, p = .044). CONCLUSION: Females received a shorter course of IO than males. However, there was no significant difference in the treatment discontinuation rate due to toxicity between males and females receiving IO. Toxicity-related treatment change was associated with COPD.

Pelvic lymphadenectomy: Evaluating nodal stage migration and will rogers effect in bladder cancer.

INTRODUCTION: Pelvic lymphadenectomy (PLND) alongside radical cystectomy (RC), provides crucial diagnostic and therapeutic value in patients with bladder cancer. With the advent of neoadjuvant chemotherapy and prospective data supporting standard PLND, controversy remains regarding the optimal PLND extent and patient selection. Nearly 40% of patients may not receive adequate PLND, even though 25% of patients have positive lymph nodes (LN) at time of RC. We hypothesized that PLND still remains an important facet of bladder cancer treatment. To clarify the prognostic importance of nodal yield, we performed a retrospective investigation of a heterogenous population (pTanyNx/0M0) of patients undergoing RC. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) program, we identified pTanyNx/0M0 bladder cancer patients undergoing RC from 2004 to 2015. Kaplan Meier curves and Cox proportional hazards models assessed cancer-specific survival. Patients were analyzed with PLND performed as the primary covariate. Survival analysis then stratified patients undergoing PLND by LN yield, both as a continuous and categorial variable (≤10, 11-20, 21-30, and >30), and T stage. RESULTS: The final cohort included pTanyNx/0M0 patients with urothelial bladder cancer (n = 12,096); median follow up was 39 (IQR: 17-77) months. PLND was performed in 81.45% of patients with a median LN yield of 14 (IQR: 7-23). Most commonly, patients had T2 disease (44.68%). After controlling for age and T stage, patients receiving PLND had improved CSS (HR = 0.56, [95% CI: 0.51-0.62]) compared to those that did not receive PLND. When grouping patients by LN yield, survival improved in a "dose dependent" manner (>30 LN: HR = 0.76, [95% CI: 0.66-0.87]). We noted similar results when stratifying patients into non-muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC). CONCLUSIONS: In a large contemporary series of pTanyNx/0M0 bladder cancer patients, we found a significant oncologic benefit to PLND. Higher LN yield correlated to improved CSS in non-muscle-invasive and muscle-invasive disease. Our data support the possibility of occult micrometastasis even in non-muscle-invasive disease. Additionally, in light of recent advances in adjuvant immunotherapy, our results emphasize the importance of adequate nodal yield for accurate staging and optimal treatment.

Extended versus standard pelvic lymph node dissection yields no difference in 3-year biochemical recurrence rates.

Background: extended pelvic lymph node dissection (ePLND) increases the detection rate of lymph node positive prostate cancer compared to a standard pelvic lymph node dissection (sPLND). However, improvement of patient outcomes remains questionable. Here we report and compare 3-year postoperative PSA recurrence rates between patients that underwent sPLND versus ePLND at the time of prostatectomy. Methods: 162 patients received a sPLND (which involvedremoval of periprostatic, external iliac, and obturator lymph nodes bilaterally), and 142 patients received an ePLND (which involved removal of periprostatic, external iliac, obturator, hypogastric, and common iliac nodes bilaterally). Decision to undergo ePLND versus sPLND at our institution was changed in 2016 based on the National Comprehensive Cancer Network guideline. The median follow-up time was 7 and 3 years for sPLND and ePLND patients, respectively. All node-positive patients were offered adjuvant radiotherapy. Kaplan-Meier analysis was carried out to assess the impact of a PLND on early postoperative PSA progression-free survival. Subgroup analyses were done for node-negative and node-positive patients, as well as Gleason score. Results: Gleason score and T stage were not significantly different between patients who received an ePLND and sPLND. The pN1 rate for ePLND and sPLND were 20% (28/142) and 6% (10/162), respectively. There was no difference in the use of adjuvant treatments in the pN0 patients. Significantly, more ePLND pN1 patients received adjuvant androgen deprivation therapy (25/28 vs. 5/10 P = 0.012) and radiation (27/28 vs. 4/10 P = 0.002). Yet, no difference in biochemical recurrence between ePLND and sPLND was observed (P = 0.44). This remained true in subgroup analyses of node-positive (P = 0.26), node-negative (P = 0.78), Gleason Score 6-7 (P = 0.51), and Gleason Score 8-10 (P = 0.77). Conclusions: PLND provided no additional therapeutic benefit, even though ePLND patients were significantly more likely to have node-positive disease and undergo adjuvant treatment, compared to a sPLND.

Annual trends of cystectomy complications: A contemporary analysis of the NSQIP database.

INTRODUCTION: Despite significant morbidity, radical cystectomy (RC) is standard of care for muscle invasive bladder cancer, certain high-risk nonmuscle invasive tumors and after failure of intravesical or trimodal therapy. Modern efforts have hastened the recovery after this surgery without impact on overall complication rates. Our primary aim was to examine changes in complication rates of RC over time. METHODS: The National Surgical Quality Improvement Program database included 11,351 RC from 2006 to 2018 for nondisseminated bladder cancer. Baseline characteristics and complication rates were studied across time periods: 2006 to 2011, 2012 to 2014, and 2015 to 2018. Thirty-day complications, readmissions, and mortality were identified. RESULTS: Overall complication rates decreased over time (56.5%, 57.4%, 50.6%, P < 0.01). Infectious complications were stable, including UTIs (10.1%, 8.8%, 8.3% respectively, P = 0.11) and sepsis (10.4%, 8.8%, 8.7% respectively, P = 0.20). On multivariable analysis, ASA≥3 (OR 1.399, 95% CI 1.279-1.530) was associated with increased complications, while procedures in 2015 to 2018 (OR 0.825, 95% CI 0.722-0.942), laparoscopic/robotic approach (OR 0.555, 95%CI 0.494-0.622), and ileal conduit (OR 0.796, 95% CI 0.719-0.882) were associated with decreased complication rates. Other outcomes of interest included mean length of stay (LOS), which decreased over time (10.5, 9.8, 8.6 days, respectively, P < 0.01) and readmission (20.0%, 21.3%, 21.0%, respectively, P = 0.84) and mortality rates were stable (2.7%, 1.7%, 2.0%, respectively, P = 0.13). CONCLUSION: Decreased early complications and LOS after RC over time may reflect beneficial effects of recent advances in bladder cancer treatment such as enhanced recovery after surgery protocols and minimally invasive techniques. Further opportunities to improve long term outcomes, readmissions and infection rates are needed.

Wound Complication Rates after Inguinal Lymph Node Dissection: Contemporary Analysis of the NSQIP Database.

BACKGROUND: Inguinal lymph node dissection (ILND) is used for diagnosis and treatment in penile cancer (PC), vulvar cancer (VC), and melanomas draining to the inguinal lymph nodes. However, ILND is often characterized by its morbidity and high wound complication rate. Consequently, we aimed to characterize wound complication rates after ILND. STUDY DESIGN: The NSQIP database was queried for ILND performed from 2005 to 2018 for melanoma, PC, or VC. Thirty-day wound complications included wound disruption and superficial, deep, and organ-space surgical site infection. Multivariable logistic regression was performed with covariates, including cancer type, age, American Society of Anesthesiologists score ≥3, BMI ≥30, smoking history, diabetes, operative time, and concomitant pelvic lymph node dissection. RESULTS: A total of 1,099 patients had an ILND with 92, 115, and 892 ILNDs performed for PC, VC, and melanoma, respectively. Wound complications occurred in 161 (14.6%) patients, including 12 (13.0%), 17(14.8%), and 132 (14.8%) patients with PC, VC, and melanoma, respectively. Median length of stay was 1 day (interquartile range 0 to 3 days), and median operative time was 152 minutes (interquartile 83 to 192 minutes). Readmission rate was 12.7%. Wound complications were associated with longer operative time per 10 minutes (odds ratio 1.038, 95% CI 1.019 to 1.056, p < 0.001), BMI ≥30 (odds ratio 1.976, 95% CI 1.386 to 2.818, p < 0.001), and concomitant pelvic lymph node dissection (odds ratio 1.561, 95% CI 1.056 to 2.306, p = 0.025). CONCLUSIONS: Predictors of wound complications after ILND include BMI ≥30, longer operative time, and concomitant pelvic lymph node dissection. There have been efforts to decrease ILND complication rates, including minimally invasive techniques and modified templates, which are not captured by NSQIP, and such approaches may be considered especially for those with increased complication risks.

Chemotherapy Refractory Spindle-Cell Rhabdomyosarcoma of the Bladder Treated With Consolidative Ovarian-Sparing Radical Surgery.

We present a case of chemotherapy refractory spindle cell rhabdomyosarcoma of the lower urinary tract in a 15-month-old female that ultimately required consolidative surgery with cystectomy, urethrectomy, ovarian-sparing hysterectomy, bilateral salpingectomy, anterior vaginal wall resection, and bilateral pelvic lymph node dissection. Genitourinary reconstruction was performed by ileal conduit creation and vaginoplasty. After completion of her maintenance postoperative chemotherapy regimen, the patient has remained disease-free for approximately 27 months.

Molecular testing in non-small cell lung cancer: A consensus recommendation.

Introduction: Lung cancer remains an important cause of cancer-related mortality in Singapore, with a greater proportion of non-smokers diagnosed with non-small cell lung cancer (NSCLC) in the past 2 decades. The higher prevalence of targetable genomic alterations in lung cancer diagnosed in Singapore compared with countries in the West, as well as the expanding therapeutic landscape for NSCLC in the era of precision medicine, are both factors that underscore the importance of efficient and effective molecular profiling. Method: This article provides consensus recommendations for biomarker testing for early-stage to advanced NSCLC. These recommendations are made from a multidisciplinary group of lung cancer experts in Singapore with the aim of improving patient care and long-term outcomes. Results: The recommendations address the considerations in both the advanced and early-stage settings, and take into account challenges in the implementation of biomarker testing as well as the limitations of available data. Biomarker testing for both tumour tissue and liquid biopsy are discussed. Conclusion: This consensus statement discusses the approaches and challenges of integrating molecular testing into clinical practice for patients with early- to late-stage NSCLC, and provides practical recommendations for biomarker testing for NSCLC patients in Singapore.

Does Time to Adjuvant Chemotherapy after Radical Cystectomy Affect Survival in Muscle Invasive Bladder Cancer? A Systematic Review.

(1) Purpose: To assess the survival benefit for different times to adjuvant chemotherapy after a radical cystectomy. (2) Materials and Methods: We systematically searched PubMed®, Cochrane Central®, Scopus®, and Web of Science® library databases for original articles that looked at timing to adjuvant chemotherapy after radical cystectomy. Primary endpoints were five-year survival, progression free survival, and overall survival. Available multivariable hazard ratios and corresponding 95% CIs were included in the qualitative analysis. The risk of bias was completed for nonrandomized studies. (3) Results: Using PRISMA guidelines, our electronic search resulted in a total of 1862 records. After a detailed review, we selected four studies that addressed the impact of the timing of adjuvant chemotherapy for patients who underwent radical cystectomy. (4) Conclusion: A survival benefit was seen with an earlier administration of adjuvant chemotherapy, albeit a benefit persists for delayed chemotherapy post-radical cystectomy. A safe and ethical approach at this time would be to administer adjuvant chemotherapy as early in the postoperative period as possible, given the known survival benefit of such therapy (9-11% absolute survival benefit at five years).

The use of blue-light cystoscopy in the detection and surveillance of nonmuscle invasive bladder cancer.

Nonmuscle invasive bladder cancer is associated with a high risk of recurrence as well as progression to muscle-invasive disease. Therefore, adequate visualization and identification of malignant lesions as well as complete resection are critical. Traditional white-light cystoscopy is limited in its ability to detect bladder cancer, specifically carcinoma in situ. Blue-light cystoscopy makes use of the intravesical instillation of a heme precursor to differentiate areas of malignancy from normal tissue. A narrative review of the literature on the use of blue-light cystoscopy in bladder cancer was conducted. Blue-light cystoscopy has been shown in several randomized clinical trials to increase detection of Ta, T1, and carcinoma in situ, as well as reduce risk of recurrence at 12 months as compared with traditional white-light cystoscopy. Research into the effects of blue-light cystoscopy on risk of disease progression has produced mixed results, in part due to changing definitions of progression. However, more recent research suggests a correlation with decreased risk of progression. Whereas the use of blue-light was initially limited to rigid cystoscopy in the operating room, results from a recent randomized clinical trial showing enhanced detection of recurrent disease using blue-light in-office surveillance flexible cystoscopy have led to expanded Food and Drug Administration approval. Overall, blue-light cystoscopy offers promise as an enhancement to white-light cystoscopy for the detection of nonmuscle invasive bladder cancer and may yield additional benefits in reducing disease recurrence and progression. Further prospective research is needed to evaluate the true benefit of blue-light cystoscopy in terms of disease progression as well as the cost-effectiveness of this technique.

Modern Management of Localized Renal Cell Carcinoma- Is Ablation Part of the Equation?

While the gold-standard for management of localized renal cell carcinoma (RCC) is partial nephrectomy, recent ablative strategies are emerging as alternatives with comparable rates of complications and oncologic outcomes. Thermal ablation, in the form of radiofrequency ablation and cryoablation, is being increasingly accepted by professional societies, and is particularly recommended in patients with a significant comorbidity burden, renal impairment, old age, or in those unwilling to undergo surgery. Maturation of long-term oncologic outcomes has further allowed increased confidence in these management strategies. New and exciting ablation technologies such as microwave ablation, stereotactic body radiotherapy, and irreversible electroporation are emerging. In this article, we review the existing management options for localized RCC, with specific focus on the oncologic outcomes associated with the various ablation modalities.

Role of metastasectomy in the management of renal cell carcinoma.

Treatment of metastatic renal cell carcinoma (mRCC) has evolved with the development of a variety of systemic agents; however, these therapies alone rarely lead to a complete response. Complete consolidative surgery with surgical metastasectomy has been associated with improved survival outcomes in well-selected patients in previous reports. No randomized control trial exists to determine the effectiveness of metastasectomy. Therefore, reviewing observational studies is important to best determine which patients are most appropriate for metastasectomy for mRCC and if such treatment continues to be effective with the development of new systemic therapies such as immunotherapy. In this narrative review, we discuss the indications for metastasectomies, outcomes, factors associated with improved survival, and special considerations such as location of metastasis, number of metastases, synchronous metastases, and use of systemic therapy. Additionally, alternative treatment options and trials involving metastasectomy will be reviewed.