Background and objective: Patients receiving immune checkpoint blockade (ICB) therapy may experience periods of prolonged disease control without a need for systemic therapy. Treatment-free survival (TFS) is an important measure for this period, but no data are available for patients with metastatic renal cell carcinoma (mRCC) starting first-line agents. Our aim was to analyze TFS outcomes for patients with mRCC starting first-line therapy.
Methods: We analyzed data for patients with mRCC starting first-line systemic therapy with VEGFR-targeted monotherapy, an ICB + VEGFR combination, or an ICB doublet from February 1, 2014 to February 1, 2023 from the multicenter International Metastatic RCC Database Consortium (IMDC) database. We estimated 36-mo TFS as the difference in restricted mean survival time between (1) the time to first-line therapy discontinuation and (2) the time to subsequent systemic therapy initiation.
Key findings and limitations: The study population included 3758 patients receiving either first-line VEGFR monotherapy (n = 2635), an ICB + VEGFR combination (n = 354), or doublet ICB (n = 769) were included. For the IMDC favorable-risk cohort, the 36-mo TFS estimate was 3.1 mo (95% confidence interval [CI] 1.5-4.6) for the VEGFR monotherapy group and 3.7 mo (95% CI 0.2-7.2) for the ICB + VEGFR group. For the IMDC intermediate-/poor-risk cohort, TFS was 2.1 mo (95% CI 1.4-2.8) for the VEGFR monotherapy group, 3.7 mo (95% CI 1.0-6.4) for the ICB + VEGFR group, and 5.3 mo (95% CI 3.8-6.8) for ICB doublet group. Limitations include the retrospective design and an inability to quantify time spent with adverse events.
Conclusions and clinical implications: Our study demonstrates that patients with IMDC intermediate or poor risk treated with ICB doublet therapy experienced longer TFS than those treated with VEGFR monotherapy in the first-line setting. These results emphasize the utility of TFS as an informative endpoint and provide survival estimates to inform decision-making in mRCC.
Patient summary: For patients with metastatic kidney cancer, we compared the survival time free from a second treatment line for different first-line treatment options. The results show that the time free from second-line treatment was longer when first-line treatment was with a combination of two immunotherapy drugs (ipilimumab and nivolumab) in comparison to other treatment options.
Categorization of patients according to their characteristics may simplify decision-making, but it fails to account for the continuous nature of risk and individual variability. Artificial intelligence has the ability to handle more complex continuous data for more precise, individualized recommendations, but several challenges must be overcome to unlock this potential.
Background and objective: A standardized intraoperative frozen section analysis of the prostate resection margin adjacent to the neurovascular bundle according to the NeuroSAFE technique is performed to maximize nerve sparing during radical prostatectomy (RP) for prostate cancer (PCa). The aim of this review was to analyze oncological and functional outcomes of NeuroSAFE.
Methods: A systematic search of the Medline, Embase, and Web of Science databases until July 2024 was performed. Studies were eligible if these included men undergoing RP with NeuroSAFE for PCa, and reported on oncological and/or functional outcomes. A cumulative analysis with random-effect models for oncological outcomes was conducted using Review Manager software, together with a narrative analysis of the procedure and functional outcomes.
Key findings and limitations: We analyzed 14 studies with nine distinct patient populations; 7505 out of 15 446 patients underwent NeuroSAFE. The number of nerve-sparing procedures was higher for patients with NeuroSAFE than for controls in all studies. Cumulative analyses showed a statistically significantly lower risk of positive surgical margins (PSMs) in favor of NeuroSAFE (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.51-0.91, I2 = 79%) and no difference in 2-yr biochemical recurrence (BCR; OR 0.79, 95% CI 0.53-1.18, I2 = 63%). All studies with control groups showed higher potency rates in the NeuroSAFE group; none reported significant difference in continence rates. Adverse events were scarce. Limitations of the studies include a lack of randomization resulting in a selection bias; the overall risk of bias judgment ranged from low to serious.
Conclusions and clinical implications: We present the first systematic review on NeuroSAFE during RP. The level of evidence is weak. The increased rate of nerve-sparing surgery, reduced PSMs, similar BCR, and low adverse event rates imply that NeuroSAFE is an oncologically safe technique. NeuroSAFE seems to improve functional outcomes, especially potency, but results of randomized trials are awaited.
Patient summary: We know that for patients with prostate cancer who undergo an operation to remove the prostate, sparing the nerve bundles next to each side of the prostate improves continence and erectile function. In this literature review, we evaluated a technique (NeuroSAFE) that aids surgeons in deciding whether they can spare these nerve bundles safely while still operating radically, for example, remove all cancer. We found that the technique is oncologically safe. Furthermore, the impact on potency appears promising but needs further study.
Current epidemiological indicators reflect the prevalence of prostate-specific antigen (PSA) testing rather than the actual incidence of clinically significant prostate cancer. These indicators are also biased because of the variability of the PSA test. We therefore need to adopt new reliable criteria in causal epidemiological studies and screening programs.
Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation. Molecular biomarkers were also evaluated in separate multivariable analyses using CPHMs that accounted for clinical characteristics. Median patient age was 70 yr; 78% of the cohort were male and 65% had pure UC histology. Median PFS was shorter for patients with CDKN2A alterations (4.6 vs 6 mo; p = 0.024) and for patients with CDKN2B alterations (4.4 vs 6 mo; p = 0.008). Median OS was longer for patients with high tumor mutational burden (13.6 vs 8.3 mo; p = 0.014). ORR was higher for patients with TSC1 alterations (87% vs 51%; p = 0.018). In multivariable analyses, CDKN2A and CDKN2B alterations were associated with inferior median PFS. This multi-institutional retrospective study of patients with aUC identified potential biomarkers associated with EV monotherapy outcomes that should be further investigated. PATIENT SUMMARY: We investigated genetic changes in urinary tract tumors that might be associated with response to enfortumab vedotin (EV) treatment in patients with advanced disease. Survival after EV treatment was longer for tumors with a higher number of mutations than for tumors with fewer mutations. However, mutations in two genes (CDKN2A and CDKN2B) were associated with worse outcomes after EV treatment. These findings will not affect current clinical practice, but should be investigated further in future studies.
Background and objective: Survivors of testicular germ cell tumor (TGCT) may experience long-term cognitive changes. The aim of our prospective study was to longitudinally assess cognitive function among TGCT survivors to identify potential lasting cognitive changes over a period of 5 yr.
Methods: TGCT survivors (n = 151) completed Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaires annually, with median time to first follow-up visit (FUV) of 8 (range 4-24) yr since completion of treatment. Treatment after orchiectomy included: active surveillance (AS) alone (n = 21); chemotherapy (CTx; n = 109); radiotherapy (RT) to the retroperitoneum (n = 11); and combined CTx + RT (n = 10). Scores for four FACT-Cog domains and overall cognitive scores were evaluated annually for 5 yr. In a subgroup analysis we compared results for survivors who received cisplatin at a dose of <400 mg/m2 (n = 48) versus ≥400 mg/m2 (n = 70).
Results: The CTx + RT group had persistently lower scores for the perceived cognitive abilities (CogPCA) domain annually between the first and fifth FUVs in comparison to the AS group (all p < 0.05), with lower overall cognitive scores from the second to the fifth FUV (all p < 0.03). The group that received ≥400 mg/m2 cisplatin had lower CogPCA scores at the first and second FUVs, and lower overall cognitive scores at the second FUV in comparison to the AS group. However, no significant change in cognitive scores across all domains was observed over 5 yr for all survivors.
Conclusions: Cognitive impairment in TGCT survivors persisted over long-term follow-up. Survivors who received both CTx and RT consistently had the worst cognitive performance at all FUVs over a 5-yr period. In addition, survivors who received a higher cisplatin dose showed worse cognitive function at all FUVs.
Patient summary: Our study results show that survivors of testicular cancer experienced long-term cognitive dysfunction that persisted over time. Survivors who underwent both chemotherapy and radiotherapy and those who received a higher dose of chemotherapy had the worst cognitive problems.
Background and objective: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is increasingly used for primary staging in prostate cancer. Owing to accurate detection of small metastases on PSMA-PET/CT, patient selection for robot-assisted radical prostatectomy (RARP) has likely changed. This study analyzes oncological outcomes in patients undergoing RARP and extended pelvic lymph node dissection (ePLND) after PSMA-PET/CT staging, compared with those without PSMA-PET/CT.
Methods: Patients who underwent staging with PSMA-PET/CT before RARP and ePLND ("PSMA cohort"; 2016-2021) were compared with patients staged without PSMA-PET/CT ("historical cohort"; 2013-2016). Propensity score matching using preoperative variables was performed to limit confounding. As primary outcome measure of biochemical recurrence (BCR)-free survival (BFS) was analyzed, with BCR defined as a prostate specific antigen value of ≥0.2 ng/ml or start of additional therapy after surgery.
Key findings and limitations: After matching, 880 patients were included (440 in each cohort). The median follow-up was 35 mo (interquartile range 21-60) for the entire cohort. In the PSMA cohort, 126/440 patients (29%) experienced BCR versus 205/440 (47%) in the historical cohort (log-rank test p = 0.032). A multivariable Cox regression analysis showed an independent effect of preoperative PSMA-PET/CT staging on BFS (hazard ratio 0.70, 95% confidence interval 0.55-0.89, p = 0.0030).
Conclusions and clinical implications: Patients who underwent staging with PSMA-PET/CT had longer biochemical progression-free survival after RARP and ePLND than those without PSMA-PET/CT. This suggests that PSMA-PET/CT staging alters patient selection for RARP and ePLND, and is associated with improved early oncological outcomes for patients who still undergo surgery.
Patient summary: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) at the diagnosis of prostate cancer leads to better visualization of metastases and therefore better selection of prostate cancer patients for surgery. Patients who underwent a PSMA-PET/CT scan at the time of diagnosis showed improved oncological outcomes, including longer progression-free survival and less prostate-specific antigen persistence after surgery.
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