Label-Free SERS of Urine Components: A Powerful Tool for Discriminating Renal Cell Carcinoma through Multivariate Analysis and Machine Learning Techniques.

The advent of Surface-Enhanced Raman Scattering (SERS) has enabled the exploration and detection of small molecules, particularly in biological fluids such as serum, blood plasma, urine, saliva, and tears. SERS has been proposed as a simple diagnostic technique for various diseases, including cancer. Renal cell carcinoma (RCC) ranks as the sixth most commonly diagnosed cancer in men and is often asymptomatic, with detection occurring incidentally. The onset of symptoms typically aligns with advanced disease, aggressive histology, and unfavorable prognosis, and therefore new methods for an early diagnosis are needed. In this study, we investigated the utility of label-free SERS in urine, coupled with two multivariate analysis approaches: Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) and Support Vector Machine (SVM), to discriminate between 50 RCC patients and 44 healthy donors. Employing LDA-PCA, we achieved a discrimination accuracy of 100% using 13 principal components, and an 88% accuracy in discriminating between different RCC stages. The SVM approach yielded a training accuracy of 100%, a validation accuracy of 99% for discriminating between RCC and controls, and an 80% accuracy for discriminating between stages. The comparative analysis of raw and normalized SERS spectral data shows that while raw data disclose relative concentration variations in urine metabolites between the two classes, the normalization of spectral data significantly improves the accuracy of discrimination. Moreover, the selection of principal components with markedly distinct scores between the two classes serves to alleviate overfitting risks and reduces the number of components employed for discrimination. We obtained the accuracy of the discrimination between the RCC patients cases and healthy donors of 90% for three PCs and a linear discrimination function, and a 88% accuracy of discrimination between stages using six PCs, mitigating practically the risk of overfitting and increasing the robustness of our analysis. Our findings underscore the potential of label-free SERS of urine in conjunction with chemometrics for non-invasive and early RCC detection.

Time to progression is the main predictor of survival in patients with high-risk nonmuscle invasive bladder cancer: Results from a machine learning-based analysis of a large multi-institutional database.

BACKGROUND: In patients affected by high-risk nonmuscle invasive bladder cancer (HR-NMIBC) progression to muscle invasive status is considered as the main indicator of local treatment failure. We aimed to investigate the effect of progression and time to progression on overall survival (OS) and to investigate their validity as surrogate endpoints. METHODS: A total of 1,510 patients from 18 different institutions treated for T1 high grade NMIBC, followed by a secondary transurethral resection and BCG intravesical instillation. We relied on random survival forest (RSF) to rank covariates based on OS prediction. Cox's regression models were used to quantify the effect of covariates on mortality. RESULTS: During a median follow-up of 49.0 months, 485 (32.1%) patients progressed to MIBC, while 163 (10.8%) patients died. The median time to progression was 82 (95%CI: 78.0-93.0) months. In RSF time-to-progression and age were the most predictive covariates of OS. The survival tree defined 5 groups of risk. In multivariable Cox's regression models accounting for progression status as time-dependent covariate, shorter time to progression (as continuous covariate) was associated with longer OS (HR: 9.0, 95%CI: 3.0-6.7; P < 0.001). Virtually same results after time to progression stratification (time to progression ≥10.5 months as reference). CONCLUSION: Time to progression is the main predictor of OS in patients with high risk NMIBC treated with BCG and might be considered a coprimary endpoint. In addition, models including time to progression could be considered for patients' stratification in clinical practice and at the time of clinical trials design.

Post-Pandemic Aftermath: A Two-Year Follow-Up of the Effect of COVID-19 on Oncological Outcomes after Radical Prostatectomy for Prostate Cancer.

PURPOSE: This study aimed to evaluate the indirect effect of the Coronavirus Disease 2019 (COVID-19) pandemic on the surgical outcomes and oncological results of patients who underwent surgery during the lockdown period. METHODS: We analysed data from 423 patients who underwent radical prostatectomy between 2016 and 2022, with a cut-off date of March 16, 2020. Patients were categorised into two groups, namely, pre-lockdown (n = 289) and during lockdown (n = 134). Perioperative variables, histopathological findings and oncological outcomes, including prostate-specific antigen (PSA) levels and biochemical recurrence (BCR), were assessed. RESULTS: The number of radical prostatectomy increased by 24.26% during lockdown. The study included patients with a mean follow-up of 21 months. A nonsignificant trend towards a higher PSA level at presentation was found (14.22 vs. 12.53 ng/dL, p = 0.216). The International Society of Urological Pathology grade was not significantly different among radical prostatectomy specimens (p = 0.669). Lymph node involvement increased during the COVID-19 period (p = 0.046). The pT classification in prostatectomy specimens increased during the pandemic, but the difference from the pre-pandemic value was not statistically significant. The BCR rates were 24.6% pre-lockdown and 29.9% during lockdown (p = 0.136). CONCLUSIONS: The COVID-19 pandemic led to poor postoperative results. Through a 2-year follow-up, this research investigated the effect of the pandemic on the oncological outcomes, particularly BCR, of patients who underwent radical prostatectomy. Further extended investigations and multi-institutional studies should be conducted to quantify the effect of the pandemic on various cancer outcomes and inform crisis management strategies.

Comprehensive Analysis of Perioperative Factors Influencing the Risk of Biochemical Recurrence in Patients with Radical Prostatectomy.

PURPOSE: To analyze the perioperative factors that influence the risk of biochemical recurrence (BCR) in patients with localized PCa undergoing radical prostatectomy Materials and Methods: A total of 457 patients, operated by 2 surgeons in our high-volume oncological center were included in the initial database. Patients who underwent RP for clinically localized PCa in our clinic from 2016 to 2021 were included in the study. Perioperative data were retrospectively reviewed for this study. Follow-up data including post-operative PSA and adjuvant treatment was prospectively gathered by contacting the patients or from the follow-up consultation. Final database was composed of 366 patients who underwent open or 3D laparoscopic RP. Statistical analysis was performed to emphasize the most powerful parameters that influence the BCR.  Results: Accounting for multivariable analysis, 4 parameters were statistically significant: initial PSA (iPSA), Gleason score, vascular involvement and positive surgical margins. For the group of patients with no positive margins, 3 parameters were statistically significant: iPSA above 10,98 ng/mL (AUC=0,71); lymph node involvement and Gleason score. Multivariable Cox regression showed that positive margins and iPSA had a significant impact on the time to BCR. Patients that received adjuvant therapy were excluded from the study. Out of the whole cohort, 27,3% of patients presented BCR. CONCLUSION: Perioperative factors need to be carefully analyzed and a detailed follow-up needs to be conducted in order to assess the risk of biochemical recurrence, resulting in the optimal time for adjuvant treatment implementation.

Evaluation of predictive factors for i-CLARAS (intraoperative complications in laparoscopic renal and adrenal surgery): a multicentre international retrospective cohort study.

The laparoscopic approach represents the standard of treatment for renal and adrenal diseases, and its use is increasing even outside referral centres. Although most procedures are routinely performed, intraoperative complications do not occur, and the rate and predictive factors of these complications have not been established. The aim of this study was to evaluate the incidence and type of intraoperative complications and to identify predictive factors in patients undergoing laparoscopic renal and adrenal surgery. This was a cohort, multicentre, international retrospective study. Patients who underwent laparoscopic renal and adrenal surgeries between April 2017 and March 2022 were included in the study. Bivariate analysis was performed using contingency tables and the χ2 test for independent samples to compare qualitative variables and the T test and Mood test for continuous variables. Multivariate analysis was performed using a logistic regression model to obtain adjusted odds ratios. A total of 2374 patients were included in the study. Intraoperative complications were reported for 8.09% of patients who underwent renal surgery, with the most common complications reported being hollow viscus and vascular complications, and for 6.75% of patients who underwent adrenal surgery, with the most common complication reported being parenchymatous viscous complications. Multivariate analysis revealed that both adrenal and renal surgery radiological preoperative factors, such as invasive features during adrenalectomy and the RENAL score during nephrectomy, are predictive factors of intraoperative complications. In contrast to existing data, surgeon experience was not associated with a reduction in the incidence of perioperative complications.

Post-Pandemic Aftermath: A Two-Year Follow-Up of the Effect of COVID-19 on Oncological Outcomes after Radical Prostatectomy for Prostate Cancer

Purpose: This study aimed to evaluate the indirect effect of the Coronavirus Disease 2019 (COVID-19) pandemic on the surgical outcomes and oncological results of patients who underwent surgery during the lockdown period. Methods: We analysed data from 423 patients who underwent radical prostatectomy between 2016 and 2022, with a cut-off date of March 16, 2020. Patients were categorised into two groups, namely, pre-lockdown (n = 289) and during lockdown (n = 134). Perioperative variables, histopathological findings and oncological outcomes, including prostate-specific antigen (PSA) levels and biochemical recurrence (BCR), were assessed. Results: The number of radical prostatectomy increased by 24.26% during lockdown. The study included patients with a mean follow-up of 21 months. A nonsignificant trend towards a higher PSA level at presentation was found (14.22 vs. 12.53 ng/dL, p = 0.216). The International Society of Urological Pathology grade was not significantly different among radical prostatectomy specimens (p = 0.669). Lymph node involvement increased during the COVID-19 period (p = 0.046). The pT classification in prostatectomy specimens increased during the pandemic, but the difference from the pre-pandemic value was not statistically significant. The BCR rates were 24.6% pre-lockdown and 29.9% during lockdown (p = 0.136). Conclusions: The COVID-19 pandemic led to poor postoperative results. Through a 2-year follow-up, this research investigated the effect of the pandemic on the oncological outcomes, particularly BCR, of patients who underwent radical prostatectomy. Further extended investigations and multi-institutional studies should be conducted to quantify the effect of the pandemic on various cancer outcomes and inform crisis management strategies (AU)