Perioperative Serum MicroRNA 371a-3p and 372-3p Levels in Patients with Clinically Localized Testicular Masses.

Background: MicroRNAs (miRNAs) show promise as blood-based tumor markers for germ cell tumors (GCTs), with miRNA-371-3p being the most studied. The marginal benefit of including other candidate miRNAs to aid with the management of testicular GCTs remains unclear. Objective: To assess the performance of our combined miRNA assay (371a-3p and 372-3p) in patients with clinically localized testicular masses. Design setting and participants: This was a retrospective review of patients prospectively enrolled in an ongoing protocol collecting serum miR-371a-3p and miR-372-3p levels (together, Memorial Sloan Kettering Cancer Center [MSK] miRNA assay [MMA]) in patients with a suspected or diagnosed testicular GCT. Outcome measurements and statistical analysis: The coprimary outcomes of interest were sensitivity and specificity of miR-371a-3p and 372-3p, individually and together, to detect nonteratomatous GCTs in the orchiectomy specimen. Secondary outcomes included additional assay diagnostic parameters, the relationship of patient and disease factors with variations in miRNA levels, and temporal patterns of miRNA normalization after orchiectomy. Results and limitations: Sixty-two patients were included, 52 had a viable GCT at orchiectomy, and ten had no cancer or a non-GCT. Forty-six patients with a GCT had positive preorchiectomy MMA (sensitivity 88.5% [95% confidence interval {CI}: 79.8, 97.2]), and one patient had positive preorchiectomy MMA but no GCT (specificity 90.0% [95% CI: 71.4, 100]). The diagnostic performance of miR-371a-3-p and miR-372-3p was similar. The time for miRNA to decrease to undetectable levels varied, with some patients having positive levels up to 3 wk after orchiectomy. Conclusions: The biomarkers miR-371a-3p and miR-372-3p demonstrated high sensitivity and specificity for localized testicular GCTs, but causes of variation in relative miRNA levels and time to normalization for individual patients remain unclear. Patient summary: We studied the ability of the blood-based biomarkers miR-371a-3p and miR-372-3p to detect testicular cancer (germ cell tumors) in patients with small testicular masses. We found that together and individually these were sensitive and specific for testicular cancer.

Long-term Clinical Outcomes of Patients With Negative Pathology (pN0) at Primary Retroperitoneal Lymph Node Dissection.

BACKGROUND: Patients who undergo primary retroperitoneal lymph node dissection (pRPLND) for early-stage testicular cancer and have no cancer (pN0) found in the retroperitoneum are believed to have an excellent prognosis. However, some experience relapse, potentially due to limitations of current staging methods. We aim to describe long-term outcomes and relapse patterns among a contemporary cohort of patients found to be pN0 at pRPLND to identify opportunities for improved diagnostic approaches and optimal patient selection. METHODS: We reviewed our prospectively maintained database for patients who underwent pRPLND for nonseminomatous germ cell tumors at our tertiary cancer center during the period from January 1, 2000, through September 30, 2023 (n = 628). We excluded 282 patients with node-positive pathology for a final analytic cohort of 346 patients. Our primary outcome was recurrence-free survival (RFS). Secondary outcomes included timing and location of recurrence. RESULTS: Of 346 included patients with pN0 pathology, 23 experienced relapse with a 2-year RFS rate of 93% (95% confidence interval: 90, 96). Most recurrences (70%) occurred in the lungs and within 6 months of pRPLND. Serum tumor markers were positive in 43% of patients at the time of relapse. All patients who relapsed were treated with salvage chemotherapy; 6 patients required additional surgical procedures. There was no testis cancer-related deaths. CONCLUSIONS: Two-year RFS for patients with pN0 pRPLND pathology is excellent. All recurrences were outside of the retroperitoneum, suggesting subclinical distant metastases at time of surgery and the benefits of a bilateral template dissection. Improved diagnostics may help better identify patients with disease within or outside of the retroperitoneum prior to pRPLND, helping guide treatment decisions.

Retroperitoneal Lymph Node Dissection in Patients with Stage II Seminomatous Germ Cell Tumour.

Treatment de-escalation strategies in patients with seminoma with retroperitoneal metastases are being investigated in ongoing clinical trials. Primary retroperitoneal lymph node dissection conducted by expert surgeons may avoid any cytotoxic treatment and related long-term side effects in ≥70% of patients with clinical stage IIA/B seminoma.

Long-term Outcomes of Regressed or "Burnt Out" Primary Testicular Germ Cell Tumors.

OBJECTIVE: To review the presentation and long-term oncologic outcomes of patients with regressed ("burnt out") primary testicular germ cell tumors (GCT). Certain testicular GCT can present with complete regression of the primary tumor. It is not well established if this is associated with more aggressive disease or worse oncologic outcomes. METHODS: We queried our prospectively maintained testicular cancer clinical database at a tertiary cancer center and identified patients without prior chemotherapy who had regressed primary GCT at radical orchiectomy from 1990 to 2023. All specimens were reviewed by a genitourinary pathologist at diagnosis. Long-term clinical outcomes were reported by Kaplan-Meier method. RESULTS: Fifty-six patients met inclusion criteria; at diagnosis, 17 had no evidence of extra-testicular disease and 39 had advanced (clinical stage [CS] II+) GCT. All CSx (no viable disease or germ cell neoplasia in situ at orchiectomy, and no evidence of advanced disease) and CS0 patients were managed with surveillance and had 5-year recurrence-free survival (RFS) of 88% (95% CI: 39%, 98%). All patients with CS II+ disease underwent primary treatment with surgery (n = 5) or first-line chemotherapy (n = 34). Two- and 5-year RFS for patients with CSII+ disease was 94% (95% CI: 78%, 98%) and 90% (95% CI: 72%, 97%), respectively. CONCLUSION: Patients with regressed primary testicular GCT often present with advanced disease, possibly due to lack of early clinical signs from the primary tumor. Our analysis shows excellent long-term oncologic outcomes similar to those reported in the literature for patients with viable primary testicular GCT.

MicroRNA for Prediction of Teratoma and Viable Germ Cell Tumor after Chemotherapy.

MicroRNAs (miRNAs) are emerging as highly sensitive and specific markers for testicular germ cell tumors (GCTs) across the spectrum of disease. However, their utility in specific clinical scenarios requires further study. Here, we review the current evidence for miRNAs as tumor markers for the evaluation of treatment response in patients undergoing chemotherapy for the treatment of advanced testicular GCT.

Patterns of Smoking Cessation Strategies and Perception of E-cigarette Harm Among Bladder Cancer Survivors.

BACKGROUND: Cigarette smoking is the leading preventable cause of bladder cancer (BC). Some proponents of e-cigarettes describe their use as a risk mitigation strategy despite potential carcinogen exposure and uncertain long-term risks. OBJECTIVE: We assessed smoking cessation strategies, including e-cigarette use, and harm perception among patients with BC. METHODS: We performed a cross-sectional study on a convenience sample of patients with BC at a single institution from August 2021 - October 2022. The survey instrument was sourced from the Cancer Patient Tobacco Use Questionnaire (C-TUQ) from the American Association for Cancer Research with standardized questions on tobacco use, cessation questions, and e-cigarette harm perceptions. RESULTS: Of the 104 surveyed BC patients (mean age: 72 years; 27% female; 55% with muscle-invasive disease), 20% were current smokers (median pack years: 40) and 51% were former smokers (median pack years: 20). A minority (9%) had quit smoking at the time of diagnosis. Pharmacotherapy for smoking cessation included nicotine patches (25%), gum (21%), lozenges (8%), e-cigarettes (8%), and Varenicline/Bupropion (4%). Notably, 43% of patients who continued to smoke expressed willingness to switch to e-cigarettes as a cessation aid. E-cigarette users (11%) more commonly perceived e-cigarettes as non-harmful compared to former (4%) and non-smokers (4%) (P = .048), though all groups regarded e-cigarettes as equally addictive as traditional cigarettes. CONCLUSIONS: Despite the prevalence of BC survivors who continue to smoke, a significant proportion perceive e-cigarettes as a viable and less harmful cessation aid. The infrequent use of FDA-approved pharmacotherapies underscores potential implementation gaps. These findings highlight the need for further research and targeted interventions in addressing smoking cessation among BC survivors.

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

ABSTRACT 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.

Bladder Cancer Survivors Who Do Not Smoke Have Better Longitudinal Health-Related Quality of Life Measures: An Assessment of the Comparative Effectiveness and Survivorship Health in Bladder Cancer (CEASE-BC) Study.

PURPOSE: Cigarette smoking is the most common risk factor for the development of bladder cancer (BC), yet there is a paucity of data characterizing the relationship between smoking status and longitudinal health-related quality of life (HRQoL) outcomes in patients with BC. We examined the association between smoking status and HRQoL among patients with BC. MATERIALS AND METHODS: Data were sourced from a prospective, longitudinal study open between 2014 and 2017, which examined HRQoL in patients aged ≥ 18 years old diagnosed with BC across North Carolina. The QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core instrument) was administered at 3, 12, and 24 months after BC diagnosis. Our primary exposure of interest was current smoking status. Linear regression using generalized estimating equations was used to analyze the relationship between smoking status and various domains of the QLQ-C30. RESULTS: A total of 154 patients enrolled in the study. Eighteen percent were classified as smoking at 3 months from diagnosis, and packs per day ranged from < 0.5 to 2. When controlling for time from diagnosis, demographic covariates, cancer stage, and treatment type, mean differences for physical function (7.4), emotional function (5.6), and fatigue measures (-8.2) were significantly better for patients with BC who did not smoke. CONCLUSIONS: Patients with BC who do not smoke have significantly better HRQoL scores in the domains of physical function, emotional function, and fatigue. These results underscore the need to treat smoking as an essential component of BC care.

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.

Primary Retroperitoneal Lymph Node Dissection for Seminoma Metastatic to the Retroperitoneum.

PURPOSE: Primary surgical treatment with retroperitoneal lymph node dissection aims to accurately stage and treat patients with node-positive pure seminoma while avoiding long-term risks of chemotherapy or radiation, traditional standard-of-care treatments. MATERIALS AND METHODS: We reported the pathologic and oncologic outcomes of patients with pure seminoma treated with primary retroperitoneal lymph node dissection in a retrospective, single-institution case series over 10 years. The primary outcome was 2-year recurrence-free survival stratified by adjuvant management strategy (surveillance vs adjuvant chemotherapy). RESULTS: Forty-five patients treated with primary retroperitoneal lymph node dissection for pure testicular seminoma metastatic to the retroperitoneum were identified. Median size of largest lymph node before surgery was 1.8 cm. Viable germ cell tumor, all of which was pure seminoma, was found in 96% (n=43) of patients. The median number of positive nodes and nodes removed was 2 and 54, respectively. Median positive pathologic node size was 2 cm (IQR 1.4-2.5 cm, range 0.1-5 cm). Four of 29 patients managed with postoperative surveillance experienced relapse; 2-year recurrence-free survival was 81%. Median follow-up for those managed with surveillance who did not relapse was 18.5 months. There were no relapses in the retroperitoneum, visceral recurrences, or deaths. Among the 16 patients who received adjuvant treatment, 1 patient experienced relapse in the pelvis at 19 months. CONCLUSIONS: Primary retroperitoneal lymph node dissection for pure seminoma with low-volume metastases to the retroperitoneum is safe and effective, allowing most patients to avoid long-term toxicities from chemotherapy or radiation.

Surgical outcomes of cytoreductive nephrectomy in patients receiving systemic immunotherapy for advanced renal cell carcinoma.

PURPOSE: The use of systemic immune checkpoint blockade before surgery is increasing in patients with metastatic renal cell carcinoma, however, the safety and feasibility of performing consolidative cytoreductive nephrectomy after the administration of systemic therapy are not well described. PATIENTS AND METHODS: A retrospective review of patients undergoing nephrectomy was performed using our prospectively maintained institutional database. Patients who received preoperative systemic immunotherapy were identified, and the risk of postoperative complications were compared to those who underwent surgery without upfront systemic treatment. Perioperative characteristics and surgical complications within 90 days following surgery were recorded. RESULTS: Overall, we identified 220 patients who underwent cytoreductive nephrectomy from April 2015 to December 2022, of which 46 patients (21%) received systemic therapy before undergoing surgery. Unadjusted rates of surgical complications included 20% (n = 35) in patients who did not receive upfront systemic therapy and 20% (n = 9) in those who received upfront systemic immunotherapy. In our propensity score analysis, there was no statistically significant association between receipt of upfront immunotherapy and 90-day surgical complications [odds ratio (OR): 1.82, 95% confidence interval (CI): 0.59-5.14; P = 0.3]. This model, however, demonstrated an association between receipt of upfront immunotherapy and an increased odds of requiring a blood transfusion [OR: 4.53, 95% CI: 1.83-11.7; P = 0.001]. CONCLUSION: In our cohort, there was no significant difference in surgical complications among patients who received systemic therapy before surgery compared to those who did not receive upfront systemic therapy. Cytoreductive nephrectomy is safe and with low rates of complications following the use of systemic therapy.

Urologists' Perceptions and Practices Related to Patient Smoking and Cessation: A National Assessment From the 2021 American Urological Association Census.

OBJECTIVE: To assess urologists' perceptions and practices related to smoking and smoking cessation. MATERIALS AND METHODS: Six survey questions were designed to assess beliefs, practices, and determinants related to tobacco use assessment and treatment (TUAT) in outpatient urology clinics. These questions were included in an annual census survey (2021) offered to all practicing urologists. Responses were weighted to represent the practicing US population of nonpediatric urologists (N = 12,852). The primary outcome was affirmative responses to the question, "Do you agree it is important for urologists to screen for and provide smoking cessation treatment to patients in the outpatient clinic?" Practice patterns, perceptions, and opinions of optimal care delivery were assessed. RESULTS: In total, 98% of urologists agreed (27%) or strongly agreed (71%) that cigarette smoking is a significant contributor to urologic disease. However, only 58% agreed that TUAT is important in urology clinics. Most urologists (61%) advise patients who smoke to quit but do not provide additional cessation counseling or medications or arrange follow-up. The most frequently identified barriers to TUAT were lack of time (70%), perceptions that patients are unwilling to quit (44%), and lack of comfort prescribing cessation medications (42%). Additionally, 72% of respondents stated that urologists should provide a recommendation to quit and refer patients for cessation support. CONCLUSION: TUAT does not routinely occur in an evidence-based fashion in outpatient urology clinics. Addressing established barriers and facilitating these practices with multilevel implementation strategies can promote tobacco treatment and improve outcomes for patients with urologic disease.

Novel approaches to redesign surveillance strategies following orchiectomy for localized testicular cancer: a narrative review.

Background and Objective: Surveillance is the preferred management strategy for most men with clinical stage I testicular cancer after orchiectomy. However, frequent office visits, imaging tests, and laboratory studies place a significant burden on patients, which may contribute to poor compliance with guideline-recommended surveillance regimens. Identifying strategies to overcome these barriers may help improve quality of life, reduce costs, and improve adherence for patients. We reviewed evidence for three strategies that may help with surveillance redesign: telemedicine, implementing microRNA (miRNA) as a biomarker, and novel imaging protocols. Methods: A web-based literature search for novel imaging strategies, diagnostic utility of miRNA, and telehealth as they relate to early-stage testicular germ cell cancer was completed during the month of August 2022. We focused our search on contemporary PubMed-indexed and Google Scholar-registered manuscripts written in English. Supportive data sourced from current guideline statements were also included. Evidence was compiled for narrative review. Key Content and Findings: Telemedicine is a safe and acceptable platform for urologic cancer follow-up care, but it requires further study specifically among men with testicular cancer. Access to care may either be improved or reduced depending on system- and patient-level characteristics and should be implemented with this in mind. miRNA may potentially be a helpful biomarker for men with localized disease, but further research on diagnostic accuracy and marker kinetics are needed before implementing it into routine surveillance strategies or using it to deviate from long-standing surveillance regiments. Novel imaging strategies with less frequent imaging and the use of magnetic resonance imaging (MRI) instead of computed tomography (CT) appear to be non-inferior in clinical trials. However, use of MRI requires expert radiologist availability and may be more costly with a lower ability to detect small, early recurrences when used in routine practice. Conclusions: Using telemedicine, integrating miRNA as a tumor marker, and adopting less intensive imaging strategies may improve guideline-concordant surveillance for men with localized testicular cancer. Future studies are needed to assess the risks and benefits of using these novel approaches separately or together.

Attitudes, Perceptions, and Use of Cancer-based Genetic Testing Among Healthy U.S. Adults and Those With Prostate or Breast/Ovarian Cancer.

INTRODUCTION: Differences in public awareness and uptake of genetic testing among patients with inheritable cancers are not well understood. The purpose of this study is to examine self-reported rates of undergoing cancer-specific genetic testing in patients with breast/ovarian cancer vs prostate cancer from a nationally representative sample of U.S. PATIENTS: Secondary objectives include examining sources of genetic testing information and perceptions of genetic testing for both patient populations as well as the general public. METHODS: Data from the National Cancer Institute's Health Information National Trends Survey 5, Cycle 4 were used to generate nationally representative estimates of adults living in the U.S. Our exposure of interest was patient reported cancer history categorized as having: (1) either breast or ovarian cancer, (2) prostate cancer, or (3) no history of cancer. χ2 testing was used to compare differences among categorical variables. RESULTS: In a nationally representative sample of 231.7 million adults, 3.7 million adults reported a history of breast/ovarian cancer while 1.5 million patients reported a history of prostate cancer; 52.3% of patients with breast/ovarian cancer vs 1.0% with prostate cancer reported undergoing cancer-specific genetic testing (P = .001). Patients with prostate cancer were less aware of cancer-specific genetic testing than either individuals with breast/ovarian cancer or adults without a cancer history (19.7% vs 64.7% vs 35.8%, respectively; P = .003). Health care professionals were the most common source of genetic testing information for patients with breast/ovarian cancer whereas the Internet was the most common source for patients with prostate cancer. CONCLUSIONS: Our results suggest a lack of awareness and limited utilization of genetic testing among patients with prostate cancer relative to breast/ovarian cancer. Patients with prostate cancer cite the Internet and social media as sources of information, which may be an avenue for more optimal dissemination of evidence-based information.

Diversity, equity, and inclusion in genitourinary clinical trials leading to FDA novel drug approval: An assessment of the FDA center for drug evaluation and research drug trials snapshot.

To determine the distribution of race and ethnicity among genitourinary oncology trial participants leading to FDA approval of novel molecular entities/biologics. Secondarily, we evaluated whether the proportion of Black participants in clinical trials increased over time. We quired the FDA Center for Drug Evaluation and Research Drug Trials Snapshot (DTS) between 2015 and 2020 for urologic oncology clinical trials leading to FDA approval of novel drugs. Enrollment data was stratified by race and ethnicity. Cochran-Armitage Trend tests were used to examine changes in Black patient participation over years. Nine clinical trials were identified that led to FDA approval of 5 novel molecular entities for prostate and 4 molecular entities for urothelial carcinoma treatment. Trials for prostate cancer included 5202 participants of which 69.8% were White, 4.0% Black, 11.0% Asian, 3.6% Hispanic, <1% American Indian/Alaska Native or Native Hawaiian/Pacific Islander, 3% other. Trials in urothelial carcinoma had 704 participants of which 75.1% were male, 80.8% White, 2.3% Black, 2.4% Hispanic, <1% American Indian/Alaska Native or Native Hawaiian/Pacific Islander, 5% other. Black participation rates over time did not change for urothelial (P = 0.59) or the combined cancer cohort (P = 0.29). Prostate cancer enrollment trends among Black participant declined over time (P = 0.03). Participants in genitourinary clinical trials leading to FDA approval of novel drugs are overwhelmingly white. Involving stakeholders who represent the needs and interests of underrepresented populations in the design and implementation of clinical trials of novel agents may be a strategy to increase diversity, equity, and inclusion among genitourinary clinical trials.