Search

Objectives: To investigate the role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in the prediction of response to sequential intravesical therapy, gemcitabine and docetaxel (Gem/Doce), given to patients with bacille Calmette-Guérin (BCG)- naïve high-risk non-muscle-invasive bladder cancer (NMIBC)., Patients and Methods: A retrospective analysis was conducted on 115 patients who received intravesical Gem/Doce for high-risk NMIBC between January 2011 and December 2021. Data were computed as the median (interquartile range [IQR]) or mean (standard deviation [sd]). Cox regression analysis was performed to determine if neutrophilia, NLR, platelet counts, and PLR before instillation therapy were predictive of recurrence-free survival (RFS) and overall survival (OS). Predictive performance was estimated using Uno's C-statistic., Results: The median (IQR) follow-up for the overall cohort was 23 (13-36) months. The mean (sd) values for NLR, PLR and platelet counts were 3.4 (2.3), 142.2 (85.5), and 225.2 (75.1) × 10 9 /L, respectively. NLR was associated with RFS, with a hazard ratio of 1.32 (95% confidence interval CI 1.19-1.46). Concordance analysis showed that NLR had a good ability to predict RFS (C-index: 0.7, P < 0.01). The PLR and platelet count were not associated with RFS and did not predict recurrence. In terms of OS, none of these cellular inflammatory markers showed any prediction value., Conclusion: Pre-treatment NLR provides some predictive accuracy for RFS in high-risk BCG-naïve patients receiving Gem/Doce. Further prospective trials are needed to validate this finding., (© 2024 BJU International.)

Background: Guidelines lack clear recommendations regarding conservative management of micropapillary (MP) variant non-muscle invasive bladder cancer (NMIBC). Bladder-sparing therapy using intravesical Bacillus Calmette-Guerin (BCG) has been reported although there are concerns regarding recurrence and progression with this approach. Due to the ongoing BCG shortage, we have utilized sequential intravesical gemcitabine and docetaxel (Gem/Doce) as primary therapy for NMIBC, including some cases with limited MP urothelial carcinoma (MPUC). To compare oncologic outcomes of patients with non-muscle invasive MPUC and conventional UC treated with Gem/Doce., Methods: A secondary analysis of 138 patients with high-risk NMIBC treated with intravesical Gem/Doce from January 2011 to December 2021 was performed. Oncologic outcomes were compared in patients with or without MPUC using the Kaplan-Meier method., Results: Median follow-up (f/u) for all patients was 23 months (IQR 13-34). There were 129 patients with pure UC and 9 with MPUC. In those with MPUC, all were high-grade (HG), 8/9 were stage T1, 7/9 had a focal MP component (extent < 10%), 3/9 had concomitant CIS, and 2/9 had lymphovascular invasion. All MPUC tumors were re-resected, and 4 had T0, 3 had T1 HG, 1 had Ta HG, 1 had carcinoma in situ (CIS); none had residual MP or LVI tumors before Gem/Doce treatment. The 24-month high-grade recurrence-free survival was 89% and 80% in patients with MPUC and pure UC, respectively. Survival outcomes did not significantly differ between patients with and without MPUC. Four patients with MPUC experienced recurrent NMIBC after Gem/Doce, and all were treated successfully with rescue sequential intravesical valrubicin and docetaxel (Val/Doce). Pathology of these four recurrent patients revealed more aggressive histologic features in the original tumor including: multifocal tumor (3/4), T1 HG disease (4/4), concomitant CIS (2/4), and moderate MP variant extent (30%) (1/4). No patient with MPUC underwent cystectomy, experienced progression, or died at last follow-up (median f/u of 43 months)., Conclusions: Gem/Doce with Val/Doce rescue appears to have activity against carefully selected non-muscle invasive MPUC with favorable histology. Larger prospective trials are needed to validate these results., Competing Interests: Declaration of competing interest I affirm that none of the authors have a conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Nephroureterectomy is commonly performed for high-grade (HG) upper tract (UT) urothelial carcinoma (UC). However, some patients may benefit from a de-escalation of surgical management, particularly for noninvasive disease and carcinoma in situ (CIS). Bacillus Calmette-Guerin (BCG) is currently the only guideline-recommended endoluminal treatment option. Gemcitabine/Docetaxel (Gem/Doce) has shown promising efficacy as a treatment for noninvasive HG UTUC, though a comparison to BCG is lacking. We report the outcomes of patients treated with endoluminal Gem/Doce vs. BCG for UT-CIS., Methods: A single-institutional retrospective review of patients treated with Gem/Doce vs. BCG for UT-CIS was performed. Treatment was instilled via nephrostomy or retrograde ureteral catheter. In both treatment groups, induction consisted of 6 weekly instillations. Maintenance was initiated if disease-free and consisted of 6 monthly instillations in the Gem/Doce group and a reduced dose (one-tenth) 3-week course at 3 months in the BCG group. Recurrence was defined as biopsy-proven disease or HG cytology., Results: The final cohort included 53 patients with 65 upper tract units; 31 received BCG and 34 received Gem/Doce. Median follow-up was 88 and 29 months in the BCG and Gem/Doce groups, respectively. Presenting pathology included biopsy-proven CIS and HG cytology in 9.7% and 90% of the BCG group, and 8.8% and 91% of the Gem/Doce group, respectively. The 2-year estimates for recurrence-free and nephroureterectomy-free survival were 61% and 89% for the BCG group and 54% and 100% for the Gem/Doce group, respectively. Upon multivariable analysis, instillation via percutaneous nephrostomy tube was associated with an increased risk of recurrence (HR 3.89, 95% CI 1.59-9.53). The development of any symptom was not statistically different between treatment groups (P = 0.12). There were 2 treatment-related deaths that occurred, 1 within each treatment group., Conclusion: Endoluminal Gem/Doce and BCG have similar oncological outcomes and major adverse event rates in the treatment of UT-CIS. Further prospective evaluation is warranted., Competing Interests: Declaration of competing interest MO is a consultant for Abbott, Fidia, Merck, Photocure, Theralase, Urogen, Vaxiion. There are no conflicts of interest regarding the contents of this article from any of the authors. IM, HH, RLS, SM, and VP have no disclosures to make., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Simple Summary: After failing multiple treatments for non-muscle invasive bladder cancer (NMIBC), patients with this disease face the prospect of radical bladder removal. However, many patients will wish to pursue additional bladder-sparing therapies or lack candidacy for such an invasive procedure. We aimed to report on a tertiary intravesical regimen of sequential doxorubicin and gemcitabine alternating weekly with docetaxel and mitomycin (Quad Chemo) for patients with high-risk NMIBC failing multiple previous treatments. We found in a population of 29 patients with 39 treated units (bladder and/or upper urinary tracts), 80% of the units were disease-free at 3 months and 43% were disease-free at 2 years following Quad Chemo treatment. However, disease progression was a concern with an estimated 43% of patients experiencing disease progression at 5 years. Lastly, side effects were not uncommon with 19 (66%) patients reporting any side effect and 7 (24%) ultimately stopping Quad Chemo due to side effects. Background: After first-line treatment failure, patients with non-muscle invasive urothelial carcinoma (NMIUC) are recommended to undergo radical cystectomy. However, those unable to pursue radical surgery or desiring bladder preservation require effective salvage therapies. Multi-agent treatment regimens are particularly useful for targeting the complex resistance mechanisms of recurrent UC. Herein, we report a regimen of sequential doxorubicin and gemcitabine alternating weekly with sequential docetaxel and mitomycin (Quad Chemo) for patients with recurrent high-risk NMIUC. Materials and Methods: We retrospectively identified all patients sequentially treated with 50 mg of doxorubicin followed by 1000 mg of gemcitabine alternating weekly with sequential 37.5 mg of docetaxel followed by 40 mg mitomycin-C between 2007–2024. Induction consisted of 8 weekly treatments, and, if disease-free, patients were initiated on monthly maintenance treatments for 2 years. Results: In total, 29 patients (39 treated units; 26 lower urinary tract, 13 upper urinary tract) with high-grade NMIUC were included in the final analysis. The cohort had high-risk features with a median of three prior induction therapies and with 38 (97%) units presented with either biopsy-proven CIS or presumed CIS in the context of high-grade urine cytology in the absence of tumorous lesions. There were 26 recurrences during follow-up, 17 in the lower tract and 9 in the upper tract. Among all of the treated units, the complete response rate was 80%, and 1- and 2-year recurrence-free survival was 60% and 43%, respectively. In total, 10 patients experienced disease progression yielding a 5-year progression-free survival of 57%. Five patients ultimately died due to bladder cancer yielding a 5-year cancer-specific survival of 83%. A total of 19 (66%) patients reported side effects during treatment, and 7 (24%) stopped treatment secondary to side effects. Conclusions: In a high-risk heavily pre-treated cohort, Quad Chemo rescued a significant portion of patients with recurrent NMIUC from disease relapse. However, progression events were considerable in the long term. Further prospective evaluation of this treatment regimen is warranted. [ABSTRACT FROM AUTHOR]

Background: Patients with small cell lung cancer (SCLC) often respond to first-line chemoimmunotherapy. However, relapse is inevitable and is associated with a poor prognosis. Treatments for relapsed SCLC, such as lurbinectedin and topotecan, are limited bymodest efficacy and significant hematologic adverse events, leaving a need for newer therapeutic agents or regimens. The combination of gemcitabine and nabpaclitaxel is active and safe in other types of malignancies, such as pancreatic cancer. Patients and methods: We conducted a phase II trial evaluating the efficacy and safety of gemcitabine and nab-paclitaxel in patients with relapsed/refractory SCLC. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with confirmed complete or partial response. Secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety. Results: Between October 2016 and May 2021, 32 patients were enrolled. Patients were followed for a median of 9.3months (range 1.8-65.2). Median age was 65 years (range 48-81). Fifty percent of patients were female. Fifty-three percent of patients had platinum-resistant/refractory relapsed SCLC. The ORR was 28.1% (95% confidence interval [CI] 15.5-100%). Median PFS was 2.9 months (95% CI 2.4-3.6), and median OS was 9.3 months (95%CI 5.2-12.4). Seven patients (21.9%) developed grade 3 or 4 neutropenia. Conclusion: Our study showed that the combination of gemcitabine and nabpaclitaxel led to encouraging outcomes in relapsed/refractory SCLC. Further studies are needed to compare this combination with other treatments used for relapsed SCLC, including lurbinectedin, temozolomide, and topotecan. [ABSTRACT FROM AUTHOR]

Simple Summary: After failing the first-line treatment of high-risk non-muscle invasive urothelial carcinoma (NMIUC), salvage intravesical therapies are important to preserve patient quality of life and avoid radical surgery. However, some patients will develop a disease resistant to commonly used drug regimens. We aimed to evaluate a novel combinatory therapy consisting of intravesical sequential gemcitabine and cabazitaxel with concomitant systemic pembrolizumab (GCP) for patients with recurrent high-risk NMIUC of the bladder and upper urinary tracts. We found in a population of 26 patients with 31 treated units (bladder and/or upper urinary tracts) that, following GCP treatment, over half of the treated units remained disease-free at 2 years. In this highly pretreated population, the progression of disease was a concern with an estimated 30% rate of progression at 2 years. However, only 4% of the population experienced cancer-related death during this same time. Lastly, this regimen was well tolerated, with all patients completing the scheduled induction course. Growing evidence suggests that many patients with high-risk non-muscle invasive urothelial carcinoma (NMIUC) can undergo bladder-sparing management with salvage intravesical therapies. However, inherent or developed disease resistance, particularly after multiple lines of prior salvage therapy, implores the continued pursuit of new treatment combinations. Herein, we describe the outcomes of 26 patients (31 treated units; 24 lower tract, 7 upper tract) with high-risk NMIUC treated with sequential intravesical gemcitabine and cabazitaxel with concomitant intravenous pembrolizumab (GCP) at the University of Iowa from August 2020 to February 2023. Median (IQR) follow-up was 30 (IQR: 17–35) months. Treated units had a history of high-risk NMIUC with a median of four prior endoluminal inductions. Overall, 87% of units presented with CIS or positive urine cytology. The 1- and 2-year recurrence-free survival was 77% (CI: 58–88%) and 52% (CI: 30–70%), respectively. The 2-year progression-free and cancer-specific survival was 70% (CI: 44–85%) and 96% (CI: 75–99%), respectively. In total, 22/26 (85%) patients reported any adverse event and 5/26 (19%) reported a grade ≥3 adverse event; however, all patients tolerated a full induction course. These results suggest that GCP is an effective and tolerable treatment option for patients with recurrent high-risk NMIUC. [ABSTRACT FROM AUTHOR]

Purpose: Bacillus Calmette-Guérin (BCG) is currently recommended as adjuvant therapy following complete transurethral resection of bladder tumor for high-risk nonmuscle-invasive bladder cancer (NMIBC). In response to the BCG shortage, gemcitabine plus docetaxel (Gem/Doce) has been utilized at our institution in the BCG-naïve setting. We report the outcomes of patients with high-risk BCG-naïve NMIBC treated with Gem/Doce. Materials and Methods: We retrospectively reviewed patients with BCG-na ïve high-risk NMIBC treated with Gem/Doce from May 2013 through April 2021. Patients received 6 weekly intravesical instillations of sequential 1 gm gemcitabine and 37.5 mg docetaxel after complete transurethral resection of bladder tumor. Monthly maintenance of 2 years was initiated if disease-free at first followup. The primary outcome was recurrence-free survival. Survival was assessed with the Kaplan-Meier method, indexed from the first Gem/Doce instillation. Adverse events were reported using CTCAE (Common Terminology Criteria for Adverse Events) v5 (National Cancer Institute, Bethesda, Maryland). Differences were assessed with the log-rank test. Results: There were 107 patients with a median followup of 15 months included in the analysis. Patients had high-risk characteristics including 47 with any carcinoma in situ and 55 with T1 disease. Recurrence-free survival was 89%, 85% and 82% at 6, 12 and 24 months, respectively. Recurrence rates were similar between patients with or without carcinoma in situ (p=0.42). No patient had disease progression or died of bladder cancer. One patient underwent cystectomy due to end-stage lower urinary tract symptoms. Overall survival was 84% at 24 months. There were 92 adverse events (1 ≥grade 3), and 4 (4%) patients were unable to receive a full induction course. Conclusions: Gem/Doce is an effective and well-tolerated therapy for BCG-naïve NMIBC. Further investigation is warranted. [ABSTRACT FROM AUTHOR]

• Forty-one upper tract units, 90% with CIS, were treated with topical gemcitabine/docetaxel. • Treatment was well tolerated, and all patients completed induction. • Side effects were similar whether given via retrograde catheter or nephrostomy tube. • Two-year upper tract recurrence free survival was 54% after treatment. • A total of 92% of patients retained their kidney and ureter 2 years after beginning treatment. There is an unmet need for effective renal sparing treatments for upper tract urothelial carcinoma (UTUC). Gemcitabine/Docetaxel (Gem/Doce) has shown favorable efficacy in nonmuscle invasive bladder cancer. We report the outcomes of patients treated with endoluminal Gem/Doce for noninvasive high-grade UTUC. A retrospective review of patients treated with Gem/Doce for clinically noninvasive high-grade UTUC with no radiographic or endoscopically visible disease, either at diagnosis or following ablation, was performed. Treatment was instilled via nephrostomy or retrograde ureteral catheter. Induction instillations were performed weekly for 6 weeks, followed by 6 monthly instillations if disease-free. Recurrence was defined as biopsy-proven disease or high-grade (HG) cytology. Progression was defined by development of muscle invasion, metastases, or death due to cancer. Survival was assessed with the Kaplan-Meier method. The final cohort included 31 patients with 41 upper tract units, 51% of which would have been dialysis dependent with nephroureterectomy. Median (IQR) age was 74 years (68–81). Median follow-up was 29 months (IQR 20–58). Prior to treatment, 37 (90%) units presented with a localizing HG cytology (presumed occult CIS), and 4 (9.8%) with HG biopsy-proven disease. Sixteen (52%) patients reported any side effects; 5 were Grade 3 and 1 was Grade 5. Recurrence-free survival was 76%, 54%, and 40% at 1, 2, and 3 years, respectively. Five patients died from urothelial carcinoma. The 3-year progression-free and overall survival were 75% and 75%, respectively. Gem/Doce demonstrates promising safety and efficacy as a renal-sparing treatment option for high-grade UTUC in appropriately selected patients. [ABSTRACT FROM AUTHOR]

Introduction: Intravesical gemcitabine and docetaxel (Gem/Doce) has been established as a safe and efficacious salvage treatment for recurrent NMIBC since 2015. Despite widespread adoption of this regimen, long-term outcomes have not been described. We report our experience with intravesical Gem/Doce following BCG failure in a large cohort of patients with extended follow-up.Methods: We retrospectively identified 97 patients at our institution treated with Gem/Doce for high-risk NMIBC after BCG failure between 2009 and 2017. Patients received six weekly intravesical Gem/Doce instillations. Monthly maintenance for 2 years was initiated if disease free at first follow-up. Outcomes included recurrence-free survival (RFS), high-grade recurrence-free survival (HG-RFS), progression-free survival (PFS), cystectomy-free survival (CFS), cancer-specific survival (CSS), and overall survival (OS). Survival probabilities were estimated using the Kaplan-Meier method.Results: Median follow-up was 49 months. Median age was 73 years, and 71% of the cohort had CIS containing disease. Thirty five percent of the cohort had BCG-unresponsive disease. Complete response at 3-month surveillance was 74% and median duration of response was 25 months. At 1, 2, and 5 years, HG-RFS was 60%, 50%, and 30%, respectively. HG-RFS was similar among BCG-unresponsive patients and the overall cohort. During follow-up, 20 patients underwent cystectomy and 15 patients experienced disease progression. Five-year PFS, CFS, CSS, and OS were 82%, 75%, 91%, and 64%, respectively.Conclusions: In this long-term analysis, intravesical Gem/Doce for high-risk NMIBC after BCG failure yielded a 75% 5-year bladder preservation rate and a 91% 5-year cancer-specific survival rate. Further prospective trials are warranted. [ABSTRACT FROM AUTHOR]

• Gem/Doce was well-tolerated with 96% of patients completing a full induction. • Two-year recurrence free survival for the cohort was 71%. • Patients naïve to prior bladder therapy had higher recurrence free survival (79%). • For initial responders, maintenance therapy may provide benefit. Adjuvant intravesical therapy is recommended for patients with intermediate-risk NMIBC. While intravesical gemcitabine-docetaxel (Gem/Doce) has demonstrated favorable outcomes for high-risk NMIBC, its utility in the intermediate-risk setting is not well described. We report outcomes of Gem/Doce as an adjuvant treatment for intermediate-risk NMIBC. We retrospectively identified patients with intermediate-risk NMIBC by AUA criteria treated with Gem/Doce following TURBT between 2012 and 2022. Patients received weekly sequential intravesical instillations of 1 g gemcitabine and 37.5 mg docetaxel for 6 weeks. Monthly maintenance of 2 years was initiated if disease-free at first surveillance. The primary outcome was recurrence-free survival (RFS), assessed using the Kaplan-Meier method. The cohort included 77 patients with median follow-up of 26 (IQR 14–50) months. Prior to induction, 67 (87%) patients presented with Ta low-grade (LG) lesions, 3 (3.9%) with Ta high-grade (HG), 5 (6.5%) with TaLG plus focal TaHG, and 2 (2.6%) with T1LG. Thirty-three (43%) patients received previous intravesical therapy including BCG (23), mitomycin (13), and docetaxel monotherapy (12). The 2-year RFS was 71% among all patients. Treatment-naïve patients had superior RFS compared to previously treated patients (P = 0.04); 2-year estimates were 79% and 64%, respectively. Twenty-nine (38%) patients experienced adverse events; all were Grade 1 to 2 except 1 (1.3%) Grade 3 (acute oxygen desaturation). Three (3.9%) patients did not tolerate a full induction course. In this retrospective review of a heterogenous population of patients with intermediate-risk NMIBC, Gem/Doce was an effective and well-tolerated adjuvant therapy. Further prospective evaluation in this setting is needed. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Repeat BCG induction remains an option for select non-muscle invasive bladder cancer (NMIBC) patients who fail initial therapy. Alternative salvage intravesical regimens such as Gemcitabine and Docetaxel (Gem/Doce) have been investigated. We aimed to compare the efficacy BCG plus interferon a-2b (BCG/IFN) and Gem/Doce in patients with recurrent NMIBC after a single prior BCG course.Methods: The National Phase II BCG/IFN trial database and multi-institutional Gem/Doce database were queried for patients with recurrent NMIBC after one prior BCG induction course, excluding those with BCG unresponsive disease. Stabilized inverse probability treatment weighted survival curves were estimated using the Kaplan-Meier method and compared. Propensity scores were derived from a logistic regression model. The primary outcome was recurrence free survival (RFS); secondary outcomes were high-grade (HG) RFS and risk factors for treatment failure.Results: We identified 197 BCG/IFN and 93 Gem/Doce patients who met study criteria. Patients receiving Gem/Doce were older and more likely to have HG disease, CIS, and persistent disease following induction BCG (all P < 0.01). After propensity score-based weighting, the adjusted 1- and 2-year RFS was 61% and 53% after BCG/IFN versus 68% and 46% after Gem/Doce (P = 0.95). Adjusted 1- and 2-year HG-RFS was 60% and 51% after BCG/IFN versus 63% and 42% after Gem/Doce (P = 0.68). Multivariable Cox regression revealed that Gem/Doce treatment was not associated with an increased risk of failure (HR = 0.97, P = 0.89) as compared to BCG/IFN.Conclusion: Patients with recurrent NMIBC after a single induction BCG failure and not deemed BCG unresponsive had similar oncologic outcomes with Gem/Doce and BCG/IFN in a post-hoc analysis. Additional prospective studies are needed. [ABSTRACT FROM AUTHOR]