18 Background: Prostate specific antigen (PSA) detection in blood is widely used to screen for prostate cancer (PCa). However, PSA has limited utility in discriminating tumors at high risk of progression from indolent-low risk tumors, which leads to PCa overtreatment and highlights the need to identify better biomarkers for the detection of clinically significant PCa (Gleason Score; GS ≥ 7). Here, we introduce a novel mRNA GATA2 exosomal biomarker detected in urine useful to diagnose clinically significant PCa. Exosomes are 50-120 nm sized vesicles shed in body fluids that contain RNA, DNA, and protein that can be used as biomarkers to interrogate the health of the originating cells. GATA2 is a pioneer transcription factor specific to PCa, increased in aggressive tumors. Methods: To evaluate the predictive value of exosomal GATA2 mRNA levels for aggressive PCa, we isolated exosomes using ultracentrifugation in non-DRE urines from 128 males with elevated PSA serum levels (> 4ng/ml) and analyzed them according to their tissue biopsy result. Results: Importantly, prostate origin of GATA2 mRNA detected in urine exosomes was confirmed by observing that exosomal GATA2 mRNA levels significantly dropped after prostatectomy (p < 0.05). Most remarkably, GATA2 exosomal mRNA expression was significantly increased in PCa biopsy positive patients (n=88) when compared to biopsy negative males (n=28, p < 0.001). Furthermore, GATA2 levels in PCa patients were significantly associated with GS, but not with disease stage and PSA levels. Multivariable regression analysis showed that GATA2 exosomal mRNA levels are an independent factor for the diagnosis of aggressive PCa. Urine GATA2 exosome mRNA expression plus SOC (age and PSA) was associated with improved discrimination of GS ≥ 7 versus GS 6 and benign disease: AUC of SOC alone 0.59 (0.49-0.70, p value=0.083) vs SOC plus GATA2 AUC of 0.68 (95% CI, 0.58-0.78, p value=0.0004). Conclusions: The analysis of urine exosomal GATA2 mRNA in individuals with high PSA may help distinguish clinically significant PCa and reduce the number of patients that need biopsy. Future studies are focused on combining this biomarker to others, such as urine exosomal PCA3, already used in the clinic.
737 Background: The standard of care for larger localized RCC lesions is radical (RN) or partial (PN) nephrectomy. RN is increasingly utilized to maximize oncologic benefit in complex tumors. Although PN is a more technically complex procedure, its nephron-sparing nature confers lasting renal and cardiovascular benefits. We utilized the National Surgical Quality Improvement Program (NSQIP) database to elucidate predictors of perioperative morbidity in T1b-T2 RCC patients. Methods: Using the NSQIP Nephrectomy-Targeted PUF, 2,094 patients undergoing nephrectomy between 2019-2020 for localized T1b-T2 RCC were identified. Variables of interest included surgical procedure and approach, tumor stage, demographics, pre-operative laboratory values, comorbidities, infection and venothromboembolism (VTE) prophylaxis techniques, peri-operative complications, operative time, length of hospital stay, 30-day reoperations, and 30-day readmissions. Chi square test was used to analyze univariate associations between certain comorbidities and complications. Multivariate regression analysis was utilized to compare complication rates between PN and RN after adjusting for baseline characteristics and surgical approach. p<0.05 was considered statistically significant. Results: 816 patients received PN while 1,278 received RN. PN patients had an increase in the following events: 30-day readmissions (7.0% vs. 4.7%, p=0.026), major bleeds (9.19% vs. 5.56%, p=0.001), renal failure requiring dialysis (1.23% vs. 0.31%, p=0.013), and urine leak or ureteric fistulae (1.10% vs. 0.31%, p=0.025). Open surgery was associated with increased VTE, renal failure, bleeds, urine leaks or ureteric fistulae, readmissions, and reoperations. Multivariate analysis revealed that PN remained predictive of all four aforementioned events, although further adjustment for robotic approach led to a loss of significance for renal failure and ureteric fistulae. Additional patient-specific predictors of relevant complications across procedure type included bleeding disorder and dialysis for bleeds, and renal failure, steroid use, and COPD for readmissions. Conclusions: This is the first study to evaluate the new NSQIP Nephrectomy-Targeted PUF. This population-based cohort provides unique insights into nephrectomy for pT1b-T2 localized RCC. We demonstrate significant associations between PN and specific complications, modulated by particular comorbidities, although both PN and RN were exceedingly safe. This analysis supports the development of novel risk stratification tools which account for specific patient comorbidities in predicting near term risk. Improved understanding of case-specific determinants of morbidity following PN or RN may facilitate shared decision making in localized RCC management.
575 Background: Neoadjuvant chemotherapy (NAC), often with a cisplatin-based regimen, is recommended before radical cystectomy (RC), as studies have shown a modest survival benefit. However, NAC may confer toxicity and augment preoperative frailty, affecting perioperative outcomes. We investigated the relationship between NAC and 30-day RC outcomes using the National Surgical Quality Improvement Program (NSQIP). Methods: RCs performed between 2019-2020 were identified in NSQIP and the corresponding cystectomy-targeted database. Baseline demographics, comorbidities, and operative parameters were compared via Pearson’s chi-square and t-tests between patients who received NAC before RC and RC alone (RCA) groups. Patient frailty was compared using the NSQIP frailty index (mFI-5), a validated 5-item score including points for diabetes, functional status, chronic obstructive pulmonary disease, heart failure, and hypertension. Multivariable logistic regression was used to compare outcomes, adjusting for age, race, robotic or open approach, urinary diversion type, comorbidities, ASA classification, and functional status. Minor complications included superficial SSI, pneumonia, UTI, bleeding requiring transfusion, AKI, or C.diff infection. Major 30-day complications included sepsis, DVT, stroke, reintubation, renal failure, MI, PE, septic shock, wound dehiscence, deep wound infection, cardiac arrest, readmission, reoperation, or mortality. All statistical tests were two tailed, p<0.05 considered significant. Results: 4,482 RCs were identified. Of these, 1889 (42%) patients received NAC. Compared to RCA, NAC patients were younger (66.9 years vs 70.4 years, p<0.001), had higher rates of white race, being functionally independent, preoperative weight loss, and cigarette use. NAC also had lower ASA class, fewer comorbidities, and lower frailty (mFI-5 0.8 vs 0.9, p<0.001). Compared to RCA, NAC patients had more robotic cystectomies (23% vs 19%, p=0.0003), received more continent diversions, had a shorter length of stay (7.1 vs 7.8 days, p<0.001), and more commonly had pT0 tumors compared to RCA (18.4% vs 5.9%, p<0.001). On MVA, NAC patients had higher rates of minor complications, most notably increased bleeding requiring transfusion [OR 1.8; 95%CI 1.6-2.1; p<0.001]. There was no difference in major complications between NAC and RCA, except NAC was associated with higher rates of sepsis [OR 1.4; 95%CI 1.1-1.8; p=0.003]. There was no difference in 30-day need for reoperation, readmission, or mortality. Conclusions: In the largest study to date on this topic, we found that NAC for RC is often given to younger, healthier patients, and is not associated with higher rates of major complications or mortality. NAC is associated with higher rates of bleeding and sepsis, which may be related to the immunosuppressive effects of chemotherapeutics. Providers should discuss with patients the benefits and risks of NAC before RC.
270 Background: Historically, surgical management with radical prostatectomy (RP) has been a definitive treatment option only for localized prostate cancer (PCa). However, recent studies suggest an overall survival benefit to treating the primary tumor with radiation therapy in metastatic PCa (mPCa). Therefore, RP may have a role in treating mPCa, but the perioperative safety of that remains unclear. Here, we aim to compare the perioperative outcomes of RP for locally advanced, node positive, and metastatic PCa using the National Surgical Quality Improvement Project (NSQIP) database. Methods: RPs performed between 2019-2020 were identified in NSQIP and the corresponding Prostatectomy-Targeted Participant Use File. Cases were grouped into six distinct categories: T1N0M0-T2N0M0; T3N0M0; T4N0M0; T1-3N1M0; T4N1M0; and T1-4N0-1M1. Baseline age, race, and medical comorbidities were compared between the groups. Patients were then further grouped into T1-2N0M0 versus T3-4N0M0 cases to compare the effect of locally advanced disease, TanyN1M0 versus TanyN0M0 to compare the effect of node-positivity, and TanyN0M1 versus TanyN0M0 to compare the effect of metastases. 30-day outcomes, operative time, hospital length-of-stay, 30-day mortality, readmissions, reoperations, major complications, minor complications, and surgery-specific complications were compared between groups. Results: Pathologic staging was available for 5,248 RPs. Baseline demographics were largely similar, with the exceptions of increased Black race, diabetes, and smoking in the node-positive-group and increased age in the T4 group. There was a slightly higher rate of minor complications in the locally advanced (T3-4N0M0) versus localized (T1-2N0M0) group, but no significant difference in major complications, 30-day mortality, readmissions, or rectal injuries. In comparison to node-negative patients (T1-4N0M0), node-positivity (T1-4N1M0) was associated with longer operative time, LOS, and incidence of 30-day renal failure, but was otherwise not associated with a higher rate of any complication. Compared to non-metastatic cases (T1-4N0M0), metastatic cases (T1-4N0M1) were associated with a higher rate of bleeding, prolonged-NG-tube use, ureteral obstruction, and LOS. Conclusions: RP for patients with locally advanced, node positive, and metastatic prostate cancer appears to be safe; it is not associated with significantly higher rates of 30-day mortality or major complications compared to RP for localized prostate cancer. Given the potential survival benefit in treating the primary tumor in advanced disease, there may be a role for RP in treating patients with advanced PCa.
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