Clinical genitourinary cancer最新文献

Background: Real-world outcomes, especially patterns of failure, are limited for patients with muscle-invasive bladder cancer (MIBC) treated with trimodality therapy (TMT). We aim to evaluate patterns of failure after TMT for MIBC in a typical heterogeneous population.

Methods: In the national Veterans Affairs database, patients with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent definitive intent TMT between 2000-2018. Successful TMT was defined as ≥ 50% definitive radiation dose and ≥ 1 cycle chemotherapy. Endpoints of any recurrence, metastatic (nonbladder) recurrence (MR), and local (bladder) recurrence (LR) evaluated in multivariable Fine-Gray models. Times to recurrence calculated from radiation start date.

Results: In 347 patients with MIBC treated with TMT, 65% of patients were deemed ineligible for surgery while 35% were surgically eligible but elected for TMT. Median follow-up time was 77 months. Median overall survival was 32.4 months (95% CI: 28.2-36.7). 154 (44%) patients had no recurrence. 130 (37%) patients developed MR, median time 9.9 months. 117 (34%) patients developed LR, median time 8.7 months. In multivariable models, lymph node positive (LN+) disease (HR:3.31, 95% CI: 1.45-7.55, P < .01) and pretreatment hydronephrosis (HR:1.62, 95% CI:1.11-2.36, P = .01) were associated with higher rates of MR. No patient, tumor, or treatment variables were associated with LR.

Conclusions: Across a multi-institutional and heterogeneous population, TMT is an effective treatment for many real-world patients with MIBC. However, a notable proportion of patients develop MR and/or LR which emphasizes the need for post-treatment surveillance and improved treatment pathways. Identified high risk features (LN+ disease, pretreatment hydronephrosis) and other markers should be further investigated to delineate the patients at high risk of TMT failure who therefore may potentially benefit from augmented treatment, such as additional systemic therapy.

Introduction: Neoadjuvant cisplatin-based chemotherapy followed by radical surgery is the standard treatment for muscle-invasive urothelial carcinoma (MIUC). The Checkmate-274 and AMBASSADOR trials have demonstrated improvements in disease-free survival (DFS) with adjuvant immunotherapy. Consequently, this meta-analysis aimed to assess the effectiveness of strategies involving checkpoint inhibitors in managing high-risk MIUC.

Patients and methods: We searched PubMed, Embase, Cochrane, ClinicalTrials.gov, EAU24, and ASCO GU abstracts for randomized controlled trials (RCTs) comparing adjuvant PD-1 and PD-L1 inhibitors against control (placebo or observation) for MIUC. Outcomes included DFS, grade ≥3 adverse events (AEs), and overall survival (OS). Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis.

Results: In a cohort of 2220 patients from three RCTs, 1,113 (50.14%) underwent adjuvant immunotherapy. This treatment significantly increased DFS (HR 0.76; 95% CI, 0.65-0.90; P < .01), particularly in lower tract tumors (HR 0.71; 95% CI, 0.56-0.91; P < .01). No substantial DFS improvement surfaced in the upper tract subgroup (P = .28) (p-interaction = .01). PD-L1 status (p-interaction = .83) and previous neoadjuvant chemotherapy (p-interaction = .11) did not significantly affect outcomes. However, immunotherapy correlated with higher grade ≥3 AEs (RR 1.47; P < .01), with no notable difference in OS (P = .07).

Conclusions: Adjuvant PD-1/PD-L1 inhibitors notably enhance MIUC DFS, particularly in lower tract tumors, regardless of PD-L1 status. These findings support immunotherapy, especially anti-PD1, as a valuable adjuvant treatment strategy for high-risk MIUC patients.

Background: After failure of first-line chemotherapy, standard of care for advanced urothelial cancer (aUC) is immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathway. Several prognostic models (Bajorin and Bellmunt scores) have been evaluated, but only in the context of chemotherapy.

Objective: To study whether the variables in these scores and new emerging clinical and biological criteria have an impact on the probability of objective response in aUC treated with ICIs in 2nd-line setting and beyond.

Materials and methods: Between October 2016 and March 2023, we included 168 patients treated with ICIs in 2nd-line setting or more in 2 French centers. Variables of interest were selected after a literature review and collected retrospectively. Analyses used log-rank test and multivariate models (binary logistic and Cox regressions).

Results and limitations: Median age at diagnosis was 68 years. Patients presented with bladder tumors in 73.8% and upper urinary tract tumors in 26.2%. 63.7% of patients had received only one line of chemotherapy before ICIs. Median follow-up after starting ICIs was 8.9 months. The variables statistically associated with objective response were: - The presence of locally advanced or lymph node-only disease compared with visceral involvement (adjusted Odds Ratio 0.19, 95% confidence interval [0.06-0.55], P = .002) and bone-only involvement (aOR 0.22 [0.08-0.64], P = .005) - The absence of antibiotic therapy the month before/after ICIs initiation (aOR 0.31 [0.12-0.84], P = .021). Limitations included retrospective design and small number of patients included.

Conclusion: This real-life study from 2 French centers found a higher likelihood of objective response: - In the absence of antibiotic therapy at ICIs initiation: - In locally advanced or lymph node-only disease, in contrast to visceral or bone-only disease. Our results suggest that negative impact of antibiotic therapy on the response to ICIs needs to be further investigated to optimize the management of these patients.

Background: The National Comprehensive Cancer Network Bladder Cancer Guidelines recommend carboplatin and gemcitabine first-line treatment in patients with cisplatin-ineligible, metastatic urothelial cancer (mUC) -- a Category 1 recommendation. For these patients, the median overall survival is 9.3 months. While carboplatin is purported to offer a more tolerable side-effect profile, many patients still require dose-reductions, dose-delays, and hospitalizations. Given the inability for mUC patients to tolerate this palliative regimen, we aim to determine whether initiating therapy with a lower dose regimen is justified.

Methods: A single-institution retrospective analysis was conducted to review eligible patients treated with carboplatin plus gemcitabine from May 2014 through October 2022. Data collected via manual chart review included patient baseline characteristics, chemotherapy doses, reductions, delays, toxicities, and effectiveness.

Results: Forty-three patients met inclusion criteria. Nineteen patients (44%) required ≥ 1 dose reduction during therapy. Twenty-six patients (60%) started with a full-dose regimen, and 14 (54%) of those patients required a dose reduction during treatment. Seventeen patients (40%) started with a reduced-dose regimen, and 5 (29%) of those patients required a dose reduction during treatment. No patients received the anticipated 6 cycles at full dose, but 14% completed 6 cycles with dose reductions. One patient (2%) was able to tolerate >80% relative dose intensity of both carboplatin and gemcitabine.

Conclusions: Cisplatin-ineligible mUC patients were unable to tolerate full-dose carboplatin and gemcitabine. As this is a palliative regimen, it would be pertinent to consider starting therapy at a reduced dose to minimize treatment interruptions, dose omissions and side effects.

Introduction: There is no organized prostate cancer screening in Germany. The aim of this study was to investigate the development of incidence and survival in patients with primary malignant tumors of the prostate in relation to changing recommendations of prostate-specific antigen (PSA) screening in guidelines.

Methods: Age-standardized incidence rates and 5-year relative survival (RS) (period approach) were calculated using data from the cancer registry North Rhine-Westphalia with the subset of the administrative district Münster respectively for the years 1992-2019. Analyses were stratified according to TNM classification.

Results: Until 2008 overall prostate cancer incidence increased, followed by a decrease up to 2017 and another increase thereafter. The same trend was observed in nonmetastatic but not in metastatic prostate cancer. Overall 5-year RS showed an increase of 10 percentage points up to period 2005-2009, followed by a constant RS. 5-year RS of patients with distant metastases remained constant from period 2000-2004 to 2015-2019, while 5-year RS with nonmetastatic prostate cancer and lymph node metastases increased slightly.

Discussion: Overall and nonmetastatic incidence rates reflect changes of recommendation in PSA screening guidelines from the United States. Accordingly, the increase in 5-year RS might be influenced by lead time bias. Incidence and survival of metastatic prostate cancer barely suggest any association with changing PSA screening recommendations.

Conclusion: Structured early detection of metastases with additionally applied diagnostic methods might improve 5-year RS rates of metastatic prostate cancer patients.

Introduction: 1L PBC has historically been recommended for patients with la/mUC. Maintenance avelumab is recommended for patients without disease progression following 1L PBC. Real-world data on the proportion of patients eligible for maintenance avelumab are limited, and outcomes among patients ineligible for maintenance avelumab are uncertain. This study assessed the proportion of patients with la/mUC initiating 1L PBC who were maintenance-avelumab eligible and real-world outcomes following 1L PBC by maintenance-avelumab eligibility.

Methods: A retrospective, observational study was conducted using a longitudinal electronic health record-derived database comprising de-identified patient-level structured and unstructured data including adults with Ia/mUC who received ≥1 dose of 1L PBC (April 2020-January 2022). The proportion of patients eligible for maintenance avelumab (real-world stable disease, partial response, or complete response following 1L PBC) was estimated and median overall survival (mOS) assessed for maintenance avelumab-eligible and -ineligible patients.

Results: Of 336 patients with Ia/mUC treated with 1L PBC (55.4% received cisplatin-based treatment 44.6% carboplatin-based treatment); 181 (54%) were maintenance-avelumab eligible; and 138 (41%) maintenance-avelumab ineligible (17 [5%] were nonevaluable). Of 181 maintenance-avelumab-eligible patients, 67 (37.0%; 19.9% of all 1L PBC-treated patients) received maintenance avelumab. mOS (95% CI) among all 1L PBC-treated patients was 15.0 (12.2-19.6) months and among maintenance-avelumab-ineligible patients was 8.0 (6.7-10.3) months; whereas among maintenance-avelumab-eligible patients (including 37% who received maintenance avelumab), mOS was 27.6 (23.4-not reached) months.

Conclusions: In this study, approximately half of 1L PBC-treated patients were maintenance-avelumab eligible, and one-fifth received it. Real-world OS remains short for the overall 1L PBC-treated population. These results support the use of treatment-guideline preferred 1L treatment options that demonstrate survival benefit for all patients with la/mUC, and are available to patients irrespective of their eligibility for cisplatin, or response to PBC.

Background: Prostate cancer manifests in various forms, ranging from occult and localized to metastatic disease. Analyzing prostate biopsies offers insights into histopathological characteristics, enhancing disease understanding and management.

Methods: This 14-year study reviewed ultrasound-guided needle prostate biopsies, collecting data via questionnaires and medical records, focusing on Gleason group, tumor involvement percentage, and predicted cancer stage. A comparative analysis across 2 distinct 7-year intervals was conducted. Statistical analyses included the Kolmogorov-Smirnov test, chi-square test, Fisher's exact test, and Analysis of Covariance, all performed using SPSS software.

Results: Among 1,598 biopsies, 624 cases of adenocarcinoma were identified. Malignancy incidence significantly correlated positively with age, prostate-specific antigen (PSA), and PSA density (PSAD), and inversely with prostate volume and the free-to-total PSA ratio (%fPSA). Notably, 30.8% of malignancies were classified as Gleason groups 4 or 5, displaying significantly higher PSA levels. Patients with prior transurethral resection of the prostate exhibited increased malignancy rates and higher Gleason groups. Diagnostic accuracy, measured by Area Under the Curve, was 0.719 for PSA, 0.730 for %fPSA, and 0.817 for PSAD. The later phase of the study showed higher cancer detection, lower PSA levels, and a greater incidence of higher Gleason groups despite a lower predicted stage.

Conclusion: The prevalence of higher Gleason groups was similar to other studies. PSAD demonstrated greater diagnostic reliability than PSA alone. Additionally, higher malignancy rates and Gleason groups were observed in patients with prior transurethral resection of the prostate. The increase in cancer detection rates during the second period likely indicates improved biopsy candidate selection.

Introduction: Despite the rapid evolution in management of metastatic renal cell carcinoma (mRCC) over the past decade, challenges remain in accessing new therapies in some parts of the world. Despite therapeutic advancements, attrition rates remain persistently high. This study aims to assess the treatment patterns and attrition rates of patients with mRCC in oncology clinics across Turkey.

Patients and methods: Patients diagnosed with mRCC between January 1, 2008, and December 31, 2022, with first-line systemic treatment data, were retrospectively evaluated using the Turkish Oncology Group Kidney Cancer Consortium (TKCC) Database.

Results: The final analysis included a total of 1126 patients. The percentages of patients treated in the 2nd, 3rd, 4th, and 5th lines of therapy were 62.8%, 27.4%, 8.9%, and 2.1%, respectively. The drugs that were most commonly used in the groups were tyrosine kinase inhibitors (TKIs) (52.2%) and interferon (IFN)-alpha (43.3%) for the first line, TKIs (66.3%) and immunotherapy (IO) monotherapy (25.9%) for the second line, TKI (41.4%) and mTOR inhibitors (28.8%) for the third line, TKI (44.4%) and mTOR inhibitors (29%) for the fourth line, and IO monotherapy (37.5%) and TKI (25%) for the fifth line. For the first-line treatment, the primary cause of attrition was disease progression (66.4%), followed by toxicity (16.5%), death (11.2%), and patient preference (5.9%). The primary reason for attrition across all treatment lines was disease progression. Over time, the use of TKIs in first-line treatment increased, while IFN-alpha usage declined. IOs began to be utilized in earlier lines, predominantly in second-line treatment, though use of IO-based combination therapies remains limited.

Conclusion: This study underscores that despite significant progress in therapeutic options, the adoption of novel agents remains slow, and attrition rates are still high. These findings indicate a disparity in systemic therapy compared to developed countries.

Background: Neuroendocrine prostate cancer (NEPC) encompasses pure NEPC and tumors with mixed adenocarcinoma and neuroendocrine histology. While NEPC is thought to confer a poor prognosis, outcome data are sparse, making risk stratification and treatment decisions difficult for clinicians.

Methods: This retrospective study identified patients with morphological and/or immunohistochemical NEPC features on pathological review of high-grade prostate cancer cases. Median overall survival (OS) was calculated by stage and castration sensitivity. Prognostic factors were assessed via multivariate analysis. OS and progression-free survival on first-line metastatic systemic treatment were also evaluated.

Results: Of 135 NEPC cases, 25.9% had NEPC documented in the original pathological report. Mixed pathology was found in 91.9% of cases. Median OS from NEPC diagnosis was 59.2, 42.3, 14.3, 17.6 and 9.6 months for localized, nonmetastatic castration-sensitive, nonmetastatic castration-resistant, metastatic castration-sensitive and metastatic castration-resistant prostate cancer, respectively. Anemia (hazard ratio [HR]: 1.66; 95% CI 1.05-2.16; P = .031) and elevated neutrophil-lymphocyte ratio (NLR) (HR: 1.51; 95% CI 1.01-2.52; P = .045), were associated with increased risk of death on multivariate analysis. 67 patients received first-line metastatic treatment beyond androgen deprivation, with a median progression-free survival of 5.2 months and OS of 15 months. Of these, 50.7% received more than 1 line of systemic treatment.

Conclusion: We observed underdiagnosis of NEPC in pathology specimens. NEPC is associated with poorer prognosis than would be expected in pure adenocarcinoma populations, with rapid progression on first-line metastatic treatment and sharp drop-off between subsequent treatment lines. Anemia and elevated NLR were associated with poor survival.