tbuckley/cabot-search huggingface dataset:
Understanding patient and provider preferences in management of metastatic renal cell carcinoma (mRCC).
Authors: Omid Yazdanpanah, David Joseph Benjamin, Elham Vosoughi, Ali Raad, Medina Popal, Piyanuch Kongtim, Nataliya Mar, Arash Rezazadeh
Journal: Journal of Clinical Oncology (2024)

e16530 Background: First-line clear cell mRCC management has evolved to include doublet therapies containing either a tyrosine kinase inhibitor (TKI) with an immuno-oncology (IO) agent or two IO agents. Oncologists typically prescribe therapies based on guideline recommendations or their personal experience with various therapies. However, patient preferences may not be a major factor in this decision-making process. Previously published data on this topic is scarce. This study aimed to assess patient preferences in the treatment of mRCC and compare it with providers' perspectives. Methods: A single-arm, prospective study surveyed mRCC patients with a questionnaire containing descriptions of 5 possible treatment options in simple language: 1) single-agent TKI; 2) IO/IO; 3) IO/TKI; 4) phase 3 clinical trial (CT); and 5) phase 1/2 CT. Patients rated their preference for each option on a 1 (least preferred) to 10 (most preferred) scale. The same questionnaire plus de-identified patient characteristics were provided to 2 academic and 1 community oncologists. Ordinal logistic regression was used to analyze the impact of patient characteristics on each treatment ranking. Pearson’s correlation was used to calculate correlation coefficients of patients' and providers' responses. Results: A total of 48 patients were surveyed with an average age of 62. Patients' responses most frequently fell in the 7-10 category for all treatment options. Among patients, the most preferred treatment option was single-agent TKI (average score of 7.9), while the least popular one was IO/IO and early phase CTs (average score of 6.0 for both) ( p&lt;0.01). Patient variables, including sex, race, language, insurance, employment and marital status, household income, and de novo versus recurrent mRCC, were not significantly associated with a greater likelihood of picking a particular treatment option. Among oncologists, the most preferred treatment option was early and late phase CTs (average score of 7.9 and 7.4, respectively), while single-agent TKI was the least preferred choice (average score of 5.7) ( p&lt;0.01). Age and prior treatment history were independently correlated with oncologist therapy choices. Conclusions: This study highlights the differences between patient and oncologist mRCC treatment preferences. Patients appear to prefer single-agent TKIs, while clinical trial participation is the least favored. Socioeconomic factors had no impact on patient preferences, highlighting individuality. In contrast, oncologists prefer CTs and are influenced by patients’ age and prior therapies. Ultimately, this study underscores the importance of an individualized discussion with each patient, devoid of any assumptions, to evaluate their therapeutic objectives and make shared decisions. Patient education on clinical trials is also paramount.
The impact of smoking status on genomic profile in patients with renal cell carcinoma.
Authors: Phillip Pham, Rebecca Hassoun, Sandra K. Althouse, Mya Tran, Christopher A. Fausel, Bryan P. Schneider, Theodore F. Logan, Tareq Salous, Nabil Adra, Jennifer King
Journal: Journal of Clinical Oncology (2024)

e16521 Background: Cigarette smoking is a known risk factor for the development of renal cell carcinoma (RCC), and active smoking has been associated with decreased survival in patients (pts) receiving systemic targeted therapies for RCC. The impact of smoking status on tumor genomics in other malignancies has been evaluated, particularly in urothelial carcinoma. Here, we investigated the impact of smoking status on genomic alterations and outcomes in pts with RCC. Methods: Pts with history of RCC who underwent genomic sequencing between 2015-2023 at Indiana University were included. Baseline demographic and disease characteristics were summarized. Pts were classified by smoking history into either no smoking history or history of smoking, which included both pts who currently or previously smoked. Comparisons between groups were done using the Chi-square test for categorical variables and Wilcoxon test for continuous variables. Kaplan-Meier method was used to analyze progression free survival (PFS) and overall survival (OS), using the log rank test to compare groups. Results: 144 pts were included. 63 (43.8%) were never smokers, 58 (40.3%) previously smoked, and 23 (16.0%) currently smoked. 103 (71.5%) were male. Median age at diagnosis was 58yrs (range: 24-83). Pts who currently smoked had a median age of 52 yrs vs. 59yrs for both pts who previously smoked and who never smoked (p=0.021). 133 pts (92.4%) were white. Histology was 69.4% clear cell, 9.0% unclassified, 9.1% papillary, 2.1% translocation, 2.1% collecting duct, 1.4% renal medullary, 1.4% chromophobe, 1.4% poorly differentiated, 0.7% mixed, and 3.4% other. Histology did not differ based on smoking status. Rhabdoid and/or sarcomatoid features were present in 28.8% of pts. 138 pts (95.8%) had metastatic disease. 65 pts (47.1%) presented with de novo metastatic disease. Metastasis sites included lung 56.9%, regional lymph nodes (LN) 40.3%, bone 31.9%, liver 17.4%, distant LN 18.8%, and brain 6.9%. The table lists genomic alterations in patients with and without a smoking history. Overall, 2-yr PFS was 9.2% and 2-yr OS was 86.5%. 2-yr PFS in pts with a smoking history was 9.2% vs. 8.6% in pts without a smoking history. 2-yr OS in pts with a smoking history was 90.1% vs. 82.3% in pts without a smoking history (p=0.49). Conclusions: In this cohort of pts, there was a trend toward more frequent PBRM1 mutations, which have been associated with improved response to immunotherapy, in pts with a history of smoking. Larger datasets are needed to further evaluate potential genomic differences based on smoking history that may reflect increased sensitivity to particular systemic therapies. [Table: see text]
The prognosis for patients with bladder cancer with recurrence after pathologic complete response or pathologic downstaging after radical cystectomy: EUMC RC cohort study.
Authors: Jungmin Jo, Dong-Hyeon Lee
Journal: Journal of Clinical Oncology (2024)

e16613 Background: Pathologic complete response (pCR, pT0N0M0) or pathologic downstaging (pDS, &lt;pT2N0M0) for bladder cancer is associated with increased overall survival (OS). However, some patients who achieved pCR or pDS experience recurrence, but these patients have not been targeted for adjuvant immunotherapy in studies to date, and the prognosis has not been well studied. We aim to examine the prognosis for bladder cancer patients with recurrence after pCR or pDS after radical cystectomy (RC). Methods: Of the 1562 patients who underwent a RC for bladder cancer between June 1996 and November 2023, 712 (45.6%), including 29 patients who did not undergo lymph node dissection, were identified as having pCR or pDS on final pathology. Of the 712 patients, 108 (15.2%) experienced recurrence. Results: Among 712 patients, 170 (23.9%) achieved pCR, 305 (42.8%) in pT1, 140 (19.7%) in Tis, and 97 (13.6%) in Ta. Out of the 170 patients with pCR, 12 (7.1%) experienced recurrence. Among the 305 patients with pT1, recurrence occurred in 63 (20.7%), and out of the 140 patients with Tis and 97 with Ta, 24 (17.1%) and 9 (9.3%) had recurrence, respectively. Only 150 (21.1%) patients received neoadjuvant chemotherapy (NAC), and 30 (27.8%) of the 108 patients who relapsed had received NAC. The median age of 108 patients with recurrence was 66.8 years old (range 31.3–86.2), and variant histology was observed in 10 (9.3%) surgical specimens. At a median follow-up of 36.7 months, the median time to recurrence was 15.5 months (10.4–20.6). Sixty-seven patients (62%) had local recurrence or lymph node-only metastasis. The distant metastasis was most common in the lung, liver, and bone (42, 38%). Conclusions: Patients with pCR or pDS at the time of radical cystectomy should prudently undergo surveillance, as recurrence and metastasis can still develop. Future studies are needed to reinforce these findings and decide whether to receive adjuvant treatment in the post-NAC setting.
Perceptions and expectations: A study on prognostic perception and quality of life in patients with metastatic renal and bladder cancer.
Authors: Hatice Bolek, Cagatay Arslan, Mert Basaran, Irfan Cicin, Mustafa Özgüroğlu, Deniz Tural, Yüksel Ürün
Journal: Journal of Clinical Oncology (2024)

e16505 Background: In metastatic cancers, treatments are aimed at palliation, focusing on life extension and quality of life (QoL) improvement rather than cure. This study aims to investigate the alignment between patient expectations and the realistic outcomes of treatment in metastatic renal cell carcinoma (mRCC) and metastatic bladder cancer (mBC). Methods: Between 15.03.2023-15.01.2024, an online survey was conducted targeting patients with mRCC and mBC. The primary objective was to evaluate the patients’ understanding and expectations concerning curability and the anticipated outcomes of their treatments in a metastatic setting. Additionally, the study aimed to explore the impact of patients' QoL and levels of optimism on their perceptions of cure and treatment outcomes. EORTC 30.3 QoL questionnaire and Life Oriented Test (LOT) were administered. Results: A total of 169 patients participated, with a median age of 63 years.72.2% of patients assessed their general health state as "good", 13.6% as "excellent", 11.8% as "fair", and 2.4% as "poor." Out of the patients surveyed, 40.2% considered cure as "very likely," 45% as "likely," 4.7% as "a little likely," and one as "not possible." The table shows patients' perspectives on improving disease symptoms, doing daily tasks easier, and living longer with treatment. Patients' perception of cure was not affected by gender, age, treatment modality, or general health status. While only 9 patients perceived cure as "a little likely" or "not possible," this group has lower median QoL and LOT scores than those who believed cure was "very likely" or "likely." This pattern is observed in their perceptions regarding the improvement symptoms, ability to make daily life activities easier, and expectations of living longer. Conclusions: Patients with mRCC and mBC have expectations of cure from treatments that may not align with clinical realities. Prioritizing clear communication and patient participation in treatment planning, particularly around palliative care is essential for effective care delivery. [Table: see text]
Utilization of neoadjuvant chemotherapy (NAC) and pathologic outcomes in upper tract urothelial carcinoma (UTUC).
Authors: Vincent Eric Xu, Sarah Azari, Matthew Nicholas Klein, Arthur Drouaud, Phat Chang, Ryan Michael Antar, Olivia French Gordon, Armine Smith, Michael Joseph Whalen
Journal: Journal of Clinical Oncology (2024)

e16620 Background: UTUC is a rare malignancy with a poorer prognosis compared to bladder urothelial carcinoma. Radical nephroureterectomy (RNU) remains the standard treatment for high-risk UTUC. Considering the decline in renal function with RNU and promising pathologic complete response rates from the phase II trial ECOG-ACRIN 8141, NAC has emerged as a favored perioperative treatment regimen for chemo-eligible patients with high-risk UTUC. However, RCTs exploring NAC's efficacy are absent, and large-scale studies examining NAC's role and predictors for its use are scarce. Methods: This study aimed to assess trends in NAC utilization, determinants for receiving NAC, and pathologic outcomes. The National Cancer Database was queried for patients with high-grade cM0 UTUC treated with RNU from 2004-2019. Outcomes included pathologic response (pR) and pathologic complete response (pCR), defined as ≤pT1pN0/X and pT0pN0/X, respectively. Multivariate regressions were adjusted for relevant patient and tumor characteristics. Results: Of 6,436 patients treated with RNU alone and 209 with RNU and NAC, older age, greater home distance from the treatment facility, and higher comorbidity scores decreased the likelihood of receiving NAC. In contrast, higher cT stage (OR 1.72, p=0.028) and cN+ status (OR 7.40, p&lt;0.001) predicted NAC treatment. NAC was more commonly used in academic centers (OR 2.02, p&lt;0.001). Use of NAC peaked in 2016 at 10%, but dropped to ~2% by 2019. There was minimal nodal response to NAC (23.4% cN+ vs 22.0% pN+). NAC was associated with 34.0% pR and 5.3% pCR rates, increasing the likelihood of pCR (OR 57.5, p&lt;0.001). In cT2-4 UTUC, 19.3% and 7.1% of patients had pR and pCR with NAC, and NAC improved odds of pR (OR 1.78, p=0.024). Conclusions: Our study demonstrated variable NAC use for UTUC, illustrating the evolving landscape of perioperative systemic therapies. We report significant response rates even in cT2-4 UTUC. Our observed poor nodal response to NAC emphasizes the crucial role of retroperitoneal lymph node dissection in staging, regardless of NAC status. We note poor NAC utilization in non-academic settings and among patients living farther from care facilities, underscoring the need for improved care quality in the context of regionalization and multi-disciplinary approaches in UTUC management. [Table: see text]
Immunotherapy plus chemotherapy versus chemotherapy alone as first-line treatment for advanced urothelial cancer: A systematic review and meta-analysis of randomized controlled trials.
Authors: Ana Caroline Fonseca Alves, Isadora Mamede Mendes da Silva, Lorena Escalante Romero, Davi Said Gonçalves Celso, Pedro Cotta Abrahão Reis, Maria Inez Dacoregio, Carlos Stecca
Journal: Journal of Clinical Oncology (2024)

e16554 Background: Platinum-based chemotherapy (CTX) has stood as the cornerstone in the treatment of advanced urothelial cancer (aUC) for decades, with limited alternative options available. The landscape shifted with the integration of PD-1 and PD-L1 inhibitors into the therapeutic arsenal, emerging as pivotal post-platinum therapies. The exploration of their potential role in the initial treatment of aUC is now a subject of active investigation. In response to these advancements, we conducted a meta-analysis to evaluate the effectiveness of immunotherapy in the first-line management of aUC patients. Methods: A systematic search across PubMed, Embase, and Cochrane identified randomized controlled trials (RCTs) comparing PD-1 and PD-L1 inhibitors combined with CTX versus CTX alone for aUC. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAE). Heterogeneity was assessed using I 2 statistics, employing a random-effects model for analysis. Statistical analyses were performed using R software version 4.3.2. Results: Among 2,162 patients from three RCTs, 1,106 (51.16%) received immunotherapy. Combining immunotherapy to CTX demonstrated substantial improvements in both PFS (HR 0.78; 95% CI 0.70-0.86; p &lt; 0.01) and OS (HR 0.84; 95% CI 0.75-0.93; p &lt; 0.01) compared to CTX alone in the entire cohort. Enhanced PFS was observed in both Cisplatin (HR 0.71; 95% CI 0.62-0.82; p &lt; 0.01) and Carboplatin (HR 0.85; 95% CI 0.73-0.98; p = 0.03) subgroups. Significant OS benefit was restricted to the cisplatin subgroup (HR 0.80; 95% CI 0.69-0.93; p &lt; 0.01), while in the Carboplatin subgroup, the benefit was only numerical (HR 0.87; 95% CI 0.75-1.01; p = 0.06), with no significant differences between subgroups (p interaction = 0.44). Additionally, immunotherapy exhibited a higher ORR (RR 1.20; 95% CI 1.06-1.36; p &lt; 0.01), with no significant differences in grade ≥ 3 TRAE (RR 1.06; 95% CI 0.98-1.15; p = 0.13). Conclusions: These findings underscore the effectiveness of combining PD-1 and PD-L1 inhibitors with CTX, revealing improved progression-free and overall survival in aUC compared to CTX alone. As anticipated, outcomes were better in patients treated with cisplatin, reaffirming its possible superiority over carboplatin regimens. Our results provide compelling evidence supporting the combination of immunotherapy and CTX as a first-line treatment option for patients with aUC.
Bladder preservation in muscle invasive bladder cancer (MIBC): A population based analysis.
Authors: Guliz Ozgun, Bernhard J. Eigl, Sunil Parimi
Journal: Journal of Clinical Oncology (2024)

e16608 Background: Although available data supports trimodal therapy (TMT) as a bladder sparing treatment for MIBC with outcomes comparable to cystectomy, uptake in Canada is low. A retrospective evaluation in British Columbia, Canada, was undertaken to evaluate real-world outcomes in MIBC patients (pts) undergoing bladder sparing radiotherapy (RT). Methods: MIBC pts were identified from the BC Cancer registry who received RT with curative intent between Jan 1, 2002, and Dec 31, 2020. Disease free survival (DFS), overall survival (OS), and disease specific survival (DSS) were calculated for those receiving RT versus combined modality treatments. Further analysis was undertaken to identify factors associated with outcomes. Results: The population was 231 pts, predominantly male (74%), median age 81 (range: 44-95). Almost all (97%) presented with high-grade MIBC, and 67.1% had an ECOG score of 0-1. The reasons for bladder preservation were frailty/comorbidities (77.1%), pt preference (16%) and inoperability (6.9%). 170 (73.6%) pts underwent RT alone; the remainder were treated with chemoRT (16.5%), neoadjuvant chemotherapy (nCT)+RT alone (5.6%), nCT+chemoRT (3%), chemoRT+adjuvantCT (0.9%), and RT+adjuvantCT (0.4%). The median OS in the RT-only group (25.2 months, 95% CI, 19.5-31) was significantly lower than for chemoRT (39.7 months, 95% CI, 13.5-65.9, p=0.013). Pts who underwent maximal transurethral resection of the bladder tumor (TURBT) in the chemoRT group exhibited significantly prolonged OS (56.5 vs. 31.9 months, p=0.006). Pts with maximal TURBT who had a second TURBT while waiting for RT demonstrated a significant improvement, compared to those with a second TURBT due to submaximal TURBT (59.3 vs. 13.3 months, p&lt;.001). Despite these findings, DSS analysis did not show statistically significant differences between the treatment groups (p=0.38), even when stratified by maximal TURBT (p=0.207). Similarly, the median DFS did not represent a difference between the groups (26.6 vs. 22.2 months, p=0.772). Cox regression analysis revealed the absence of carcinoma in situ trended towards a decreased risk of death (HR: 0.52, p&lt;0.001), as did the absence of hydronephrosis (HR: 0.65, p=0.009) and an increase in the total number of RT fractions (HR: 0.92, p=0.001). In the analysis of treatment modalities (RT vs. chemoRT), there was a significant difference in the distribution of recurrence sites (Chi-Square=4.15, p=0.04). Local recurrences were identified less frequently in the chemoRT group. Conclusions: This population-based study showed notable demographic and treatment-related characteristics that influenced OS, DSS, and DFS. While respecting the limitations of retrospective cohort studies, overall outcomes in this cohort are inferior to those predicted for TMT, but adherence to best practices such as maximal TURBT and combined modality chemoRT result in acceptable long term survival rates.
Development and validation of a novel prognostic model for overall survival in patients with micropapillary urothelial carcinoma.
Authors: Leonidas Nikolaos Diamantopoulos, Dimitrios Korentzelos, Vasiliki Bountziouka, Konstantinos Vadikolias, Maria Lambropoulou, Gregory Tripsianis
Journal: Journal of Clinical Oncology (2024)

e16618 Background: Micropapillary urothelial carcinoma (MUC) is a rare variant of bladder cancer with limited prognostic data in the literature. We hereby present a novel prognostic model for overall (OS), for patients with MUC, derived from the Surveillance, Epidemiology and End Results (SEER) database. Methods: The SEER database (18 registries/November 2020) was queried with the case listing method by using the ICD-10 topography codes C67.0-C67.9 (bladder cancer), and the morphologic code 8131 (MUC). Patients were randomly divided into a training (TC) and a validation cohort (VC) (7:3 ratio). Variables significantly associated with OS were identified with multivariate Cox regression and backwards stepwise conditional approach; each variable received “points” according to its beta coefficient, based on the formula: Probability of an event at time t=S 0 (t) exp(β 1 x 1 , β 2 x 2 ...) , (β = regression coefficients, x = observed covariate values, S0(t) = survival function). Cumulative risk points were assigned to each patient and three distinct risk categories for OS were constructed. Harrel’s optimism-corrected C-statistic with bootstrap resampling was used for internal (TC) and external (VC) validation. Discriminatory performance of the model was compared to the AJCC 8 th edition with the likelihood ratio test (LRT). Results: 548 patients were included in the study (374 TC, 174 VC). No statistically significant differences in baseline characteristics and survival outcomes were identified between TC and VC. Age, marital status, tumor size, AJCC stage, radical cystectomy, radiation and chemotherapy were significant variables inserted in the multivariate model. Patients were stratified to three risk groups (low, intermediate, high) based on the total risk points collected (&lt;100, 100-150 and &gt;150, Table). Median OS was NR (95%CI; NR, NR), 41 (95% CI; 25-57) and 14 months (95% CI; 11-17) for the low, intermediate, and high-risk categories respectively (log-rank p&lt;.001). Optimism-corrected C-statistic for the prognostic score was 0.74 (95%CI;0.71-0.78) in the TC and 0.70 (95%CI; 0.65-0.78) in the VC. C-statistic for AJCC 8 th edition was 0.65 (95% CI; 0.61-0.69) and 0.62 (95% CI; 0.56-0.68) in the TC and VC respectively. The LRT demonstrated superior discriminatory performance of our prognostic model compared to AJCC (p&lt;.001). Conclusions: We present a novel prognostic model for OS of patients with MUC composed of clinicopathologic and treatment variables. Our model had superior performance to the AJCC system and may serve as a useful tool for individualized risk assessment in patients with MUC. [Table: see text]