Clinical genitourinary cancer最新文献

Introduction

The purpose of this study was to investigate the association between baseline androgen concentrations and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line enzalutamide or abiraterone acetate plus prednisone (AAP).

Materials and Methods

We previously randomized men with mCRPC to enzalutamide or AAP to compare side-effects and measured androgen concentrations. In this post-hoc analysis, patients were grouped in quartiles (Q) based on their serum androgen values. Kaplan-Meier and Cox regression were used to analyze progression-free and overall survival for baseline androgen groups, treatment subgroups and their interaction. The trial was registered at clinicaltrialsregister.eu (2017-000099-27).

Results

Eighty-four patients received enzalutamide and 85 AAP. Overall, higher (Q4) compared with lower (Q1) baseline serum testosterone was associated with longer progression-free survival (24.8 vs. 10.7 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.33; 0.84) and overall survival (52.8 vs. 31.5 months, HR 0.49, 95% CI 0.28; 0.85). The risk reduction in death seemed to be treatment dependent (treatment subgroup interaction P = .04). For men in the AAP subgroup, the Q4 compared with Q1 group had a significant lower risk of death (HR 0.30, 95% CI 0.13; 0.73), while no difference was found for enzalutamide (HR 0.77, 95% CI 0.35; 1.69). Similar results were found for the other androgens.

Conclusion

Pre-treatment serum testosterone levels may be a clinically useful biomarker for predicting mCRPC treatment responses and guiding treatment selection.

Objective

To evaluate the role of pelvic lymph node dissection (PLND) in patients diagnosed with high-risk nonmuscle-invasive bladder cancer (NMIBC) undergoing radical cystectomy (RC) using a national cohort of NMIBC patients.

Methods

A cohort of patients diagnosed with NMIBC cancer with urothelial carcinoma from the National Cancer Database (NCDB) between 2004 and 2019 was utilized. The cohort consists of patients who have not received BCG and underwent upfront radical cystectomy or pelvic exenteration. Kaplan–Meier analysis was utilized to assess overall survival (OS) outcomes. Cox regression was also utilized to identify independent predictors of OS.

Results

The cohort of 9399 patients was stratified by clinical T stage and then subdivided by pathological outcome. For patients with cTa, a majority received a lymph node dissection 97.74% (941/1019), amongst the entire cohort, a minority had node positive disease 3.3% (34/1019). For cTis, most patients received a lymph node dissection 94.08% (482/507), and a minority had node positive disease 5.1% (26/507). For cT1, most patients had a lymph node dissection 95.62% (6,060/6,337), and a 13.1% (832/6337) of patients had a positive lymph node. Amongst patients with cT1 disease who underwent PLND, KMA demonstrated better OS compared to patients who did not undergo PLND (P < .001).

Conclusion

The data suggests an OS benefit in patients with later stage (cT1) NMIBC. Thus, our findings support the existing clinical guidelines of pelvic lymph node dissection in patients with high-risk nonmuscle invasive bladder cancer.

Objective

The COVID-19 pandemic resulted in decreased prostate specific antigen (PSA) testing for prostate cancer screening and its impact remains uncharacterized. Our objective was to compare incident PSA testing rates, PSA levels, and prostate cancer treatment rates before and during the pandemic after the state of emergency (SoE) was declared.

Materials and Methods

This was a population-based, retrospective cohort study among men 50-80 years of age in Ontario, Canada undergoing incident PSA testing from November 23, 2018 to July 9, 2021. Working backwards and forwards from the date of the province-wide SoE (March 17, 2020), 30-day time periods were constructed during which incident PSA testing rates were measured. Our primary outcome was the rate of incident PSA testing. Secondary endpoints included comparison of incident PSA levels and prostate cancer treatment rates.

Results

We identified 835,402 men who underwent incident PSA testing. There was a 20% decrease in PSA testing after the SoE (RR = 0.80,95% CI: 0.800.81, P < .001). There was a higher proportion of extreme PSA levels after the SoE with a higher proportion of patients with a PSA >20 ng/mL (rate ratio = 1.63,95% CI: 1.54-1.73, P < .0001) and >100 ng/mL (rate ratio = 1.98,95% CI: 1.77-2.20, P < .0001). This effect was highest for those aged 50-59 years. More patients required active treatment (5,201,59.5% prior to the pandemic vs. 5,072,64.2%, P < .001 after the SoE declaration).

Conclusions

The COVID-19 SoE resulted in patients experiencing a 2-fold increase in the risk of having an extreme PSA level and higher odds of treatment. Future studies are needed to assess the impact on the rates of advanced prostate cancer and cancer-specific mortality.

Introduction

Studies comparing radical prostatectomy (RP) to radiation therapy (RT) have consistently shown that patients undergoing RT have a higher risk of other-cause mortality (OCM) compared to RP, signifying poor health status of the former patients. We aimed to evaluate the impact of RP versus RT on cancer-specific mortality (CSM) over a cohort with equivalent OCM risk.

Patients and Methods

The SEER database was queried to identify patients with nonmetastatic PCa between 2004 and 2009. Patients were matched based on their calculated 10-year OCM risk and further stratified for D'Amico Risk Score and Gleason Grade. A Cox-regression model was used to calculate the 10-year OCM risk. Propensity-score based on the calculated OCM risk were used to match RP and RT patients. Cumulative incidence curves and Competing-risk regression analyses were used to examine the impact of treatment on CSM in the matched cohort.

Results

We identified 55,106 PCa patients treated with RP and 36,674 treated with RT. After match, 6,506 patients were equally distributed for RT versus RP, with no difference in OCM rates (P = .2). The 10-year CSM rates were 8.8% versus 0.6% (P = .01) for RT versus RP in patients with unfavorable-intermediate-risk (Gleason Score 4 + 3) and 7.9% versus 3.9% (P = .003) for high-risk disease. There was no difference in CSM among RT and RP patients for favorable-intermediate-risk (Gleason Score 3 + 4) and low-risk disease.

Conclusions

In a matched cohort of PCa patients with comparable OCM between the 2 arms, RP yielded a more favorable CSM rate compared to RT only for unfavorable-intermediate- and high-risk groups.

Introduction

Our objectives were to analyse the incidence of changes in renal function after radical cystectomy (RC) and determine the factors responsible for those changes, as a basis for rethinking strategies to ensure early detection and development of a risk-adapted approach.

Patients and methods

A single-centre retrospective study included 316 patients who underwent RC between 2010 and 2019. A competing risk Cox model, whereby death from any cause was treated as a censoring event, was used to establish nomograms to analyze the prognostic factors for CKD at 2 and 5 years. The nomograms were validated based on discrimination using the C-index, calibration plots and analysis of net benefit from decision curves.

Results

During a median follow-up of 48.73 months (0.13-156.67), 138 patients (43.7%) developed CKD. The probability of CKD development at 2 and 5 years was 41.3% (95% CI, 35.8-47.2) and 48.5% (95% CI, 42.8-54.6), respectively. Hypertension (HR 1.69, 95% CI, 1.23-2.34), prior hydronephrosis (HR 1.62, 95% CI, 1.17-2.25), acute kidney injury (AKI) during the immediate postoperative period (HR 1.88, 95% CI, 1.35-2.61) and readmission due to urinary tract infection (HR 1.41, 95% CI, 1.01-1.96) were predictors of 2-year CKD. Hydronephrosis at follow-up computed tomography (HR 2.21, 95% CI, 1.60-3.07), prior hydronephrosis (HR 1.54, 95% CI, 1.09-2.15), AKI during the immediate postoperative period (HR 1.77, 95% CI, 1.27-2.46) and hypertension (HR 1.60, 95% CI, 1.16-2.21) were predictors for 5-year CKD. Prior eGFR ≥ 90 mL/min/1.73 m² was a protective factor (HR 0.50, 95% CI, 0.32-0.80 and HR 0.48, 95% CI, 0.30-0.78 for 2- and 5-year CKD, respectively). The resulting nomograms were based on these prognostic factors.

Conclusion

Almost half of the patients had developed CKD at 5 years. Thus, it is crucial to identify patients at risk of developing CKD in order to initiate renal function-sparing measures and tailor follow-up protocols. The proposed nomograms effectively predicted CKD in these patients.

Introduction

Prostate cancer (PCa) is one of the most common cancers worldwide. PCa diagnosis is mostly based on solid biopsy and prostate-specific antigen (PSA), which have the disadvantages of being invasive and insensitive, respectively. Recently, the detection of microRNAs (miRNAs) in expressed prostatic secretions (EPS) has been a promising approach for PCa diagnosis. The aim of this study is to quantify transcriptional levels of miRNA-32 in the urine of prostate cancer patients.

Materials and methods

In this study, we evaluated the expression of miRNA-32 in the urine of 27 PCa patients, 48 benign prostatic hyperplasia (BPH) and 20 healthy controls, using quantitative real-time PCR (qPCR). The expression levels were then compared with the clinicopathological characteristics of patients.

Results

The expression level of miRNA-32 in PCa patients was significantly higher than the control group (P < .01) and BPH cases (P < .01), and was associated with advanced tumor stage (P < .05). In addition, the expression of miRNA-32 had significant correlation with patients’ age (r = 0.39, P = .043). Area under ROC curve (AUC) for the discrimination of PCa samples from control and BPH samples were 0.93 (P < .0001) and 0.78 (P < .0001), respectively. We also used logistic regression analysis to integrate the results of PSA, prostate volume and miRNA-32, and presented a predictive model for distinguishing PCa from BPH, highlighting the clinical utility of miRNA-32 in cancer diagnosis and risk assessment.

Conclusions

Measurement of miRNA-32 expression in urine may have significance for the detection of PCa. Inclusion of miRNA-32 in logistic regression along with PSA and prostate volume increases the accuracy of cancer diagnosis.

Purpose

To investigate the safety and effectiveness of radiotherapy for advanced upper tract urothelial carcinoma (UTUC) patients intolerant to chemotherapy.

Methods

Data for 21 patients with advanced UTUC intolerant to chemotherapy were retrospectively collected. All patients were treated with conventionally fractionated radiotherapy (50-70 Gy/20-33 f) or partial-SABR boost to the lesions (50-60 Gy/20-25 f with tumor center boosted with 6-8 Gy/f, 3-5 f) for bulky tumors.

Results

The median age was 75 years (range, 58-87 years). Primary tumor resection was performed for all patients and none underwent metastatic resection. Seventeen (81%) patients had oligometastasis (1-5 metastases) at diagnosis. Eighteen (85.7%) received irradiation to all tumor lesions. Lymph node metastasis was predominant in the whole group (17/21). Other lesions were distributed as local recurrence (7/21), bone metastases (2/21) and abdominal wall/muscle (2/21). The median follow-up time was 38.5 months (interquartile range, 15.2-48.7 months). Rate of local control (LC), progression-free survival (PFS) and overall survival (OS) of the whole group at 1 year were 90%, 46.6%, and 80.4%, respectively. At 3 years, LC, PFS and OS were 65.6%, 26.6%, and 40.9%, respectively. Fourteen patients developed acute mild gastrointestinal toxicity, generally of grade 1-2; 8 patients developed acute grade 1-2 hematological toxicity, consisting mainly of anemia and leukopenia. No grade 3 or higher acute or late toxicities were observed.

Conclusion

For patients with advanced UTUC who are not able to tolerate chemotherapy, radiotherapy is a safe treatment and can achieve good local tumor control.

Background

To establish a nomogram predicting postoperative recurrence-free survival (RFS) in patients with nonmetastatic renal cell carcinoma (RCC) of pathological T3a (pT3a) stage undergoing nephrectomy.

Materials and Methods

A retrospective review included 668 patients with pT3a RCC between 2008 and 2019, randomly divided into training and validation groups (7:3 ratio). Cox regression analysis established the RFS-predicting nomogram in the training group. Nomogram performance was assessed using Harrell's concordance index (C-index), time-dependent receiver operating characteristic curve, decision curve analysis, and Kaplan-Meier survival analysis.

Results

Of the 668 patients with pT3a RCC, 167 patients experienced local recurrence or distant metastasis. Using multivariable Cox regression analysis, tumor size, ISUP grade, necrosis, capsular invasion, pT3a invasion pattern were identified as the significant predictors for RFS to establish the nomogram. The C-index of the nomogram was 0.753 (95% CI, 0.710-0.796) and 0.762 (95% CI, 0.701-0.822) for the training and validating group, respectively. The areas under the 1-year, 3-year and 5-year RFS receiver operating characteristic curves were 0.814, 0.769 and 0.768, respectively. Decision curve analysis showed the optimal application of the model in clinical decision-making. Patients with low risk T3a RCC have better RFS than those with high risk T3a RCC.

Conclusion

Tumor size, ISUP grade, necrosis, capsular invasion and T3a invasion patterns were independent risk factors for worse RFS in patients with nonmetastatic pT3a RCC. The current nomogram could effectively predict the RFS of patients with nonmetastatic pT3a RCC.

Background

Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with survival in patients with urothelial carcinoma (UC) treated with ICI.

Methods

Patients from 15 institutions were treated with ICI monotherapy. Primary endpoint was overall survival and secondary endpoints included observed response rate (ORR), and progression-free (PFS) calculated from ICI initiation. TMB was analyzed as dichotomous (≥10 vs. <10 mut/Mb) and continuous variable.

Results

We identified 411 patients: 203 were treated with ICI 1L/upfront; 104 with 2 + L. For the 1L/upfront: median [m] OS was numerically longer in patients with TMB ≥10 versus TMB <10: mOS 35 versus 26 months (HR = 0.6) and with MSI-H and MSI-S (mOS NR vs. 22 months), though neither association was statistically significant. A statistically significant association was found between TMB (continuous variable) and OS (HR = 0.96, P = .01). For 2 + L: mOS was numerically longer in patients with TMB ≥10 versus TMB <10: (20 vs. 12 months; HR = 0.9); mOS was 12 and 17 months for patients with MSI-H and MSI-S, respectively. Eighty-nine patients received maintenance avelumab (mAV): mOS was longer in patients with TMB ≥10 versus TMB <10: 61 versus 17 months; (HR = 0.2, P = .02) and with MSI-H and MSI-S (NR vs. 24 months).

Conclusions

Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Further validation is needed.

Objective

Patients and Method

Results

Conclusions