Clinical genitourinary cancer最新文献

Objective

Systemic therapy is guideline-recommended for metastatic urothelial carcinoma of the urinary bladder (UCUB). Unmarried status represents an important barrier to treatment access in many primaries. The importance of married status is unknown in the context of systemic therapy in metastatic UCUB and was addressed in the current study.

Methods

We relied on the Surveillance, Epidemiology, and End Results database (2004-2020) to identify patients with metastatic UCUB. Univariable and multivariable logistic regression models were fitted to address systemic therapy rates. Additionally, temporal trends were plotted.

Results

Overall, 6873 patients with stage IV UCUB were identified. Of those, 4853 (71%) were male. Of males, 2993 (62%) were married vs. 797 (39%) of females. The rates of systemic therapy were 55% in both married males and married females. Married males and females differed from their unmarried counterparts regarding age and race/ethnicity. In males, prior to any adjustment, married status was associated with an odds ratio of 1.46 (P < .001). After adjustment for age and race/ethnicity, the odds ratio increased to 1.73 (P < .001). In females, prior to any adjustment, married status was associated with an odds ratio of 1.94 (P < .001). After adjustment for age and race/ethnicity, the odds ratio decreased to 1.57 (P < .001).

Conclusion

Unmarried males and unmarried females are significantly exposed to lower access to systemic therapy compared to their married counterparts. In consequence, both unmarried men and unmarried women should be given very careful consideration when use of systemic therapy in metastatic UCUB is contemplated.

Background

Different combination therapies using anti - PD-1 / PD-L1 or CTLA-4 immune checkpoint inhibition (ICI) are widely used in patients with metastatic renal cell carcinoma (mRCC). In the absents of established biomarkers, immune-related adverse events (irAEs) have been discussed as potential predictors of response.

Methods

In this retrospective cohort study, data of 134 patients with mRCC undergoing ICI treatment (Nivolumab, Ipilimumab and Nivolumab, Pembrolizumab and Axitinib or Avelumab and Axitinib) between 2015 and 2021 were analyzed. To examine the utility of irAEs as predictors of overall survival (OS) and progression-free survival (PFS), separate Kaplan–Meier analyses and Cox proportional regression analyses were applied. Landmark analysis was conducted after 12 weeks to reduce immortal time bias.

Result

irAEs were observed in 85 patients (63.4%). Cutaneous (n = 52, 38.8%), endocrine (n = 33, 24.6%) and hepatic (n = 19, 14.2%) irAEs were most commonly observed. In Kaplan–Meier analysis, patients experiencing irAEs showed favorable median PFS (15 months, 95% CI, 9.91-20.09) compared to the non-irAE group (5 months, 95% CI, 3.56-6.44, P < .001). The median OS was 25 months (95% CI, 16.79-33.21) in the non-irAE group, while it was not reached in the irAE group (P = .002). In multivariable analysis, the presence of any irAE was associated with favorable PFS (HR 0.46 [95% CI, 0.26-0.82] P = .008) and OS (HR: 0.28 [95% CI, 0.12-0.63] P = .002), respectively. Landmark analysis after 12 weeks showed mixed results depending on the classification of the irAE group at the landmark time.

Conclusion

The presence of irAEs under ICI therapy in patients with mRCC is associated with better PFS and OS. Thus, manageable irAEs should not be cause for premature discontinuation of ICI therapy, as they seem to indicate favorable outcomes.

Considering the time-dependent nature of irAEs is crucial estimating their value as predictive markers.

Objective

To explore the clinicopathological features and prognosis of TFE3-rearranged renal cell carcinomas (TFE3-rRCC).

Methods

In this retrospective observational study, the data of patients with TFE3-rRCC admitted to Xijing Hospital from January 2010 to October 2023 were collected, encompassing the general information, pathological diagnosis, immunohistochemistry, and the results of FISH detection. The treatment information and survival data of the patients were recorded during the follow-up.

Results

A total of 55 patients with TFE3-rRCC were enrolled, among whom 25 were males and 30 were females. TFE3 FISH assay suggested the disruption of the TFE3 gene. Fifty-four patients underwent surgical resection of kidney lesions, while 1 patient did not. By the end of follow-up in December 2023, 3 patients were lost to follow-up, 28 patients remained alive, and 24 patients had died. Among the 52 patients followed up, 31 developed metastases, involving lymph nodes, liver, bone, lung, peritoneum, pleura, adrenal gland, and brain. The 1-year and 5-year survival rates of the patients were 84.6% and 50.6%, respectively. In this study, there were 31 patients with TFE3-rRCC recurrence or metastasis. Median PFS was 7 and 13 months in the VEGFR-TKI and VEGFR-TKI+ ICI groups, respectively. The median OS was 12 months in the VEGFR-TKI treatment group. The median OS data of VEGFR-TKI+ ICI group has not been reached. The ORR and DCR was 25%, 66.7% in the VEGFR-TKI group. The ORR and DCR was 33.3%, 77.8% in the VEGFR-TKI+ ICI group.

Conclusion

TFE3-rRCC is a rare subtype of malignant renal tumor. The diagnosis mainly relies on pathological morphology, immunohistochemistry, and the detection of TFE3 gene disruption by FISH. In terms of treatment, surgery is the primary approach, and lymph nodes, liver, and bone are the main metastatic sites. VEGFR-TKI+ICI treatment might be an option of recurrent or metastatic TFE3-rRCC.

Introduction

Prostate cancer (PC) is the second most common cancer among men around the world. Several smaller studies have explored the relationship between elevated PSA and mortality, but results have been conflicting. Additionally, studies have shown that Black men are more likely to be diagnosed with PC at late-stages and may have a twofold increase in mortality risk. This study aims to evaluate the relationship between PSA levels and mortality in patients with PC and differences between Black versus White patients.

Methods

In this retrospective study, the TriNetX database, was used to extract de-identified EMRs of 198,083 patients. Patients were included if they were diagnosed with PC and had obtained a PSA level (measured in ng/mL) within 6 months prior to diagnosis. Cohorts were separated into 7 groups based on intervals of PSA, ranging from < 2 to ≥ 500 and compared to a control cohort with a PSA of 4 to 20 for differing 2-year mortality rates. A subgroup analysis was performed to compare mortality differences between Black and White patients. A posthoc analysis evaluated 5- and 10-year mortality amongst all patients with PC.

Results

After propensity matching, mortality risk was significantly lower for patients with PSA < 2 (5.9% vs. 7.5%; RR 0.784; P < .001) when compared to the control cohort. Mortality was significantly higher for all other subsequent PSA intervals > 20, with the lowest risk ratios at PSA 20-100 (24.1% vs. 10.0%; RR 2.419; P < .001) and highest at PSA 200 to 500 (50.4% vs. 10.8%; RR 4.673; P < .001). The sub-group analysis showed that when compared to White patients, Black patients with PSA < 20 had similar mortalities, but had significantly lower 2-year mortality rates at PSA levels ≥ 20. The posthoc analysis of PSA levels and 5- and 10-year mortality of all patients with PC showed similar trends to the 2-year outcomes.

Conclusion

This study found that prostate cancer patients with significantly elevated PSA levels have a greater mortality, and Black patients have lower 2-year mortality rates than their White counterparts when matched for PSA levels greater than 20.

Purpose

We investigated regional differences in patients with stage III nonseminoma germ cell tumor (NSGCT). Specifically, we investigated differences in baseline patient, tumor characteristics and treatment characteristics, as well as cancer-specific mortality (CSM) across different regions of the United States.

Methods

Using the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), patient (age, race/ethnicity), tumor (International Germ Cell Cancer Collaborative Group [IGCCCG] prognostic groups) and treatment (systemic therapy and retroperitoneal lymph dissection [RPLND] status) characteristics were tabulated for stage III NSGCT patients, according to 12 SEER registries representing different geographic regions. Multinomial regression models and multivariable Cox regression models testing for cancer-specific mortality (CSM) were used.

Results

In 3,174 stage III NSGCT patients, registry-specific patient counts ranged from 51 (1.5%) to 1630 (51.3%). Differences across registries existed for age (12%-31% for age 40+), race/ethnicity (5%-73% for others than non-Hispanic whites), IGCCCG prognostic groups (24%-43% vs. 14-24% vs. 3%-20%, in respectively poor vs. intermediate vs. good prognosis), systemic therapy (87%-96%) and RPLND status (12%-35%). After adjustment, clinically meaningful inter-registry differences remained for systemic therapy (84%-97%) and RPLND (11%-32%). Unadjusted 5-year CSM rates ranged from 7.1% to 23.3%. Finally in multivariable analyses addressing CSM, 2 registries exhibited more favorable outcomes than SEER registry of reference (SEER Registry 12): SEER Registry 4 (Hazard Ratio (HR): 0.36) and SEER Registry 9 (HR: 0.64; both P = .004).

Conclusion

We identified important regional differences in patient, tumor and treatment characteristics, as well as CSM which may be indicative of regional differences in quality of care or expertise in stage III NGSCT management.

Introduction

Platinum-based chemotherapy (CTX) has historically been the primary treatment for advanced urothelial cancer (aUC), with limited alternative options. The therapeutic landscape experienced a paradigm shift following the results of the EV-302 and Checkmate-901 trials, which led to the approval of Enfortumab vedotin plus pembrolizumab (EV-P) as the preferred first-line treatment, and nivolumab plus CTX for those unable to receive the preferred regimen. Currently, further investigations are underway to explore PD-1 and PD-L1 inhibitors in the initial treatment of aUC.

Patients and methods

We conducted a systematic search across PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing immune checkpoint inhibitors (ICI)-CTX combinations versus CTX alone as first-line treatment for advanced UC. Employing a random-effects model, we pooled hazard ratios (HR) with 95% confidence intervals (CI).

Results

Our analysis encompassed 3 RCTs, involving 2162 participants, with 51.16% randomized to combination therapy with platinum-based CTX. Compared to CTX alone, immune-chemotherapy significantly improved overall survival (HR 0.84; 95% CI 0.75-0.93; P < .01), progression-free survival (HR 0.78; 95% CI 0.70-0.86; P < .01), and objective response rate (RR 1.20; 95% CI 1.06-1.36; P < .01), while elevating the risk of immune-related adverse events (P-value = .02).

Conclusion

In this meta-analysis of RCTs, ICI plus CTX demonstrated a significant association with improved survival at the expense of an increased risk of immune-related adverse events. Therefore, our findings suggest that this combination should be considered as an initial treatment for aUC in platinum-eligible patients who cannot receive EV-P.

The treatment landscape for localized and regional prostate cancer includes active surveillance, radiation therapy (RT), and radical prostatectomy (RP). Population-based studies comparing RP to radiation reveal conflicting results due to methodological flaws. This systematic review and pooled analysis of studies aim to compare cause-specific survival (CSS), overall survival (OS), disease-free survival (DFS) and toxicity outcomes, comparing RP to RT in the management of prostate cancer. This systematic review search included the PubMed, Embase, and Cochrane libraries according to the PRISMA statement with the inception of each database up to June 24, 2023. Randomized phase 2 or 3 clinical trials that compared RP to RT in prostate cancer were included. The forest plot for the Odds ratio (OR) was plotted using the Mantel–Haenszel method, and the Z test was used to assess significance. A fixed effects model was used for meta-analysis. The search yielded seven completed randomized clinical trials and four ongoing trials. The majority of complete trials had low to intermediate-risk patient populations. OR for OS was 1.00 with 95% CI, 0.71-1.41 (P-value: 0.98), CSS OR was 0.99 with 95% CI, 0.45-2.18 (P-value 0.11), OR for DFS was 1.26 with 95% CI, 0.89-1.78 (P-value 0.19) when comparing RP to RT. The rate of distant metastatic disease was 2.3% in the RP versus 2.9% in the RT at 10 years. The rate of second malignant neoplasms was 4.5% in the RP compared to 4.2% in the RT arm at 10 years. RP caused more urinary symptoms, with a predominance of the need for urinary pads and a higher incidence of sexual dysfunction, and RT caused a higher incidence of bowel symptoms, such as blood in stools and fecal incontinence. This study provides evidence that the treatment-related outcomes are similar in patients with low to intermediate-risk prostate cancer when comparing RP to RT. Multidisciplinary treatment approaches and factoring patients' values and preferences should form the cornerstone of the ideal treatment option for each patient with localized prostate cancer. Patients with prostate cancer have an equal chance of being cancer-free and alive at 10 years with either RP or RT. In terms of side effects, RP causes more urine leakage and loss of erections, whereas RT tends to cause more bowel side effects, such as blood in stools and fecal leakage.

Introduction

Metachronous metastatic prostate cancer (mmPCa) patients harbor different characteristics and outcomes, relative to DeNovo metastatic PCa patients. Onset of metastatic disease might be influenced by primary PCa characteristics such as Gleason score (GS) or cancer stage, as well as overall survival (OS) by timing of metastatic onset.

Patients and Methods

We relied on an institutional tertiary-care database to identify mmPCa patients. Kaplan Meier and Cox Regression models tested for onset of metastases and OS, stratified according to GS, pathological stage and time to mmPCa.

Results

Of 341 mmPCa patients, 8% harbored GS6 versus 41% versus 51% GS7 and GS8-10. Median time to onset of metastatic disease was 79 versus 54 versus 41 months for GS6 versus GS7 versus GS8-10 (P = .01). Moreover, median time to onset of metastases was 64 versus 44 months for pT1-2 versus pT3-4 mmPCa patients undergoing radical prostatectomy (P = .027). In multivariable Cox regression models, higher GS and pT-stage was associated with earlier onset of metastases. Additionally, significant OS differences could be observed for time interval of < 24 versus 24-60 versus 60-120 versus ≥ 120 months between primary PCa diagnosis and onset of mmPCa. Specifically, median OS was 56 versus 69 versus 97 months versus not reached (P < .01) for these categories. In multivariable Cox regression, shorter time to metastatic onset was associated with shorter OS.

Conclusion

Timing of mmPCa is strongly influenced by grading and pT-stage in real-life setting. OS benefits can be observed with longer time interval between primary PCa diagnosis and onset of mmPCa.

Background

Efficacy of treatment after failure of check point inhibitors (ICI) therapy remains ill-defined in metastatic renal cell carcinoma (mRCC).

Objective

To evaluate the safety and effectiveness of cabozantinib after failure of ICI-based therapies.

Design, setting and participants

Patients with mRCC who concluded cabozantinib treatment directly after an ICI-based therapy were eligible. Data was collected retrospectively from participating sites in Germany.

Interventions

Cabozantinib was administered as a standard of care.

Outcome measurements and statistical analysis

Adverse events (AE) were reported according to CTCAE v5.0. Objective response rate according to RECIST 1.1 and Progression Free Survival (PFS) were collected from medical records. Descriptive statistics and Kaplan-Meyer-plots were utilized.

Results and limitations

About 56 eligible patients (71.4% male) with median age of 66 years and clear cell histology in 66.1% (n = 37) were analyzed. 87.5% (n = 49) had ≥ 2 previous lines. IMDC risk was intermediate or poor in 17 patients (30.4%) and missing in 66.1%. 20 patients (35.7%) started with 60 mg. 55.4% (n = 31) required dose reductions, 26.8% (n = 15) treatment delays and 1.8% (n = 1) treatment discontinuation. Partial response was reported in 10.7% (n = 6), stable and progressive disease were reported in 19.6% (n = 11) and in 12.5% (n = 7). 32 patients were not evaluable (57.1%). Median treatment duration was 6.1 months. Treatment related AE were reported in 76.8% (n = 43) and 19.6% (n = 11) had grade 3-5. Fatigue (26.8%), diarrhea (26.8%) and hand-foot-syndrome (25.0%) were the 3 most frequent AEs of any grade and causality. SAE were reported in 21.4% (n = 12), 2 were fatal. Major limitation was the retrospective data capture in our study.

Conclusions

Cabozantinib followed directly after ICI-based therapy was safe and feasible. No new safety signals were reported. A lower starting dose was frequently utilized in this real-world cohort, which was associated with a favorable tolerability profile. Our data supports the use of cabozantinib after ICI treatment.