Pembrolizumab and concurrent radiation is an effective regimen for muscle invasive bladder cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17020-e17020
Author(s):  
Niraj K. Gupta ◽  
Chad A. Reichard ◽  
Michael Large ◽  
Christopher A. Leagre ◽  
Kenneth Ney ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Complete Response ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Female Ratio ◽  
Muscle Invasive ◽  
Radiation Treatments

e17020 Background: Neo-adjuvant chemotherapy with Gemcitabine and Cisplatin followed by radical cystectomy is the standard of care in muscle invasive bladder ca. Some patients, usually older patients or those with poor PS with bladder ca are either cisplatin in-eligble or medically unfit for radical cystectomy. We share our experience using a combination of Pembrozulimab and concurrent radiation in cisplatin in-eligible patients with muscle invasive bladder cancer. Methods: Patients with muscle invasive bladder ca underwent TURBT followed by treatment with Pembrolizumab 200 mg IV every three weeks for 4 cycles concurrent with radiation treatments. Radiation treatments were started 1 week after starting pembrolizumab. A total of 64-65 Gy was given to the bladder and pelvis. All patients underwent a cystoscopy to assess local response and imaging studies to rule out distant metastases. Results: Between June 2018 and October 2019, 9 patients with locally advanced, cT2-cT4 urothelial ca were treated. Male to female ratio 7 to 2. Median age was 76 years, range was 71-90. Reasons were not using cisplatin were, renal-insufficiency, 7 pts. and pt refusal in 2 pts. ECOG PS was 1 in 6 patients and 2 in 3 pts. All patients finished radiation treatments. All but one patient finished 4 cycles of pembrolizumab. One patient declined the last dose. Grade-3/4 I/O inhibitor AEs were seen in 2 patients, One had pneumonitis and other had elevation of LFTs. None of the patients was found to have distant mets on the scans done after 4 cycles of Pembrolizumab. A complete response, by cystoscopy (histology/cytology) was seen in 7/9 (77%) of the patients. The other 2 pts. with PR declined cystectomy and have continued on immunotherapy without any evidence of progression. Conclusions: A combination of Pembrolizumab concurrent with radiation treatments is an effective option and can be safely administered in cT2-T4 bladder cancer. It is an attractive option for cis-ineligible patients. The feasibility and efficacy of this combination needs to be further explored in larger studies

Neoadjuvant chemotherapy in muscle invasive bladder cancer: Real world data on safety and outcome.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17036-e17036
Author(s):  
Sree Vamsee Chetana Panthula ◽  
Arun Philip ◽  
Pavithran Keechilat ◽  
Wesley Mannirathil Jose
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Invasive Bladder Cancer ◽  
Definitive Treatment ◽  
Muscle Invasive Bladder Cancer ◽  
Female Ratio ◽  
Radiological Response ◽  
Muscle Invasive

e17036 Background: The standard treatment for Muscle Invasive bladder cancer (MIBC),Radical Cystectomy and Neoadjuvant chemotherapy (NACT) has shown to improve survival. Data from Indian population is scarce, and we sought to explore the efficacy, tolerability and factors affecting the outcome of Neoadjuvant chemotherapy in our population. Methods: This was a Retrospective Observational study conducted at a tertiary care centre. Patients of MIBC treated between 2008 and 2019 were included in the analysis. The NACT consisted of Gemcitabine + Cisplatin (GC) or Gemcitabine + Carboplatin (GCa). The prognostic significance of the various clinico-laboratory parameters was assessed by the log rank test. The survival analysis was done by the Kaplan Meier method. Results: Total of 40 patients received NACT from 2008-2019. The median age of study group was 62 years. Male to Female ratio was 5:1. Out of 40 patients, 26 were treated with GC and the remaining 14 received GCa. Majority (80%) patients were administered either 3 or 4 cycles of NACT. Among 18 patients who demonstrated good radiological response after NACT completion, 13 had received Cisplatin. After NACT, 32 (80%) underwent Radical Cystectomy and 3 were treated with CTRT. The remaining 5 did not receive definitive treatment. Pathological complete response (PCR) was achieved in 10 out of 32 patients (31%). Out of 10 patients with PCR, 9 belonged to Cisplatin group and only 1 in Carboplatin group. In patients with PCR, 80% remained progression free at last follow up. Grade 3/4 toxicities were minimal. However, achieving a pathological CR did not translate into significant survival benefit in our study (p value 0.10). Median follow up time and overall survival for the cohort was 29.5 and 54 months respectively. Conclusions: Gemcitabine/Cisplatin as NACT resulted in superior radiological response, PCR, PFS and OS when compared to Gemcitabine/Carboplatin in MIBC. This regimen is well tolerated and we advocate for further prospective studies with GC in this setting. [Table: see text]

Durvalumab as neoadjuvant therapy for muscle-invasive bladder cancer: Preliminary results from the Bladder Cancer Signal Seeking Trial (BLASST)-2.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 507-507 ◽  
Author(s):  
Xiao X. Wei ◽  
Bradley Alexander McGregor ◽  
Richard J. Lee ◽  
Xin Gao ◽  
Kerry L. Kilbridge ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Therapy ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Predictive Biomarkers ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive

507 Background: There is no established neoadjuvant therapy (NAT) for patients (pt) with muscle invasive bladder cancer (MIBC) ineligible for cisplatin-based chemotherapy preceding radical cystectomy. Encouraging prospective data indicate PD-1/PD-L1 inhibitors, including pembrolizumab and atezolizumab, are safe and active as NAT for MIBC. Durvalumab (D), a PD-L1 inhibitor, is FDA approved for treating locally advanced or metastatic urothelial carcinoma following platinum-based chemotherapy. The safety and activity of D as NAT in MIBC have not been reported. Methods: We are conducting a single-center sequential multicohort trial (NCT03773666) of D alone (Cohort 1, N=10) and D plus the CD73 inhibitor oleclumab (Cohort 2, N=10) in cT2-T4aN0M0 MIBC pts who are RC candidates and are ineligible for or declined cisplatin-based chemotherapy. The primary endpoint is feasibility, defined as ≥7 of 10 pts receiving at least 1 dose of D followed by radical cystectomy without dose limiting toxicity (DLT) up to 12 wks post-RC. In Cohort 1, D is administered at 750mg IV Q2W for 3 cycles followed by RC 2-4 weeks after the last dose. Baseline and RC tissue and baseline and on-study blood are collected for correlative studies, including immunohistochemistry, genomics, transcriptomics, and metabolomics. Results: Cohort 1 has completed enrollment; ten pts were enrolled between Feb 2019 to Sept 2019. Median age was 67 (Range: 53-85) and 8 (80%) were men. All 10 pts completed 3 durvalumab doses. Eight pts completed planned RC with at least 12wk follow-up post-op to date. No DLTs were observed. One Grade 3 treatment-related adverse event (trAE) was reported (anemia), with no Grade 4 or higher trAE. Pathologic response (<pT2N0) was seen in 2 of 8 (25%) pts with pathologic complete response (pT0) in 1 (12.5%) pts. Updated safety and efficacy data from Cohort 1 will be presented. Conclusions: D appears to be feasible as NAT in MIBC with preliminary evidence for antitumor activity. Toxicities are consistent with data from other PD-1/PD-L1 inhibitor trials. Future cohorts will examine D-containing combination NAT strategies. Analysis of tissue and blood-based predictive biomarkers are ongoing. Clinical trial information: NCT03773666.

scholarly journals Impact of immunohistochemistry-based subtyping of GATA3, CK20, CK5/6, and CK14 expression on survival after radical cystectomy for muscle-invasive bladder cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tanan Bejrananda ◽  
Kanet Kanjanapradit ◽  
Jirakrit Saetang ◽  
Surasak Sangkhathat
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Intensive Therapy ◽  
Invasive Bladder Cancer ◽  
Clinicopathological Parameters ◽  
Double Negative ◽  
Muscle Invasive Bladder Cancer ◽  
Female Ratio ◽  
Muscle Invasive ◽  
Male To Female

AbstractMolecular subtyping of muscle-invasive bladder cancer (MIBC) predicts disease progression and treatment response. However, standard subtyping based on transcriptomic analysis is relatively expensive. This study tried to use immunohistochemistry (IHC) to subtype MIBC based on GATA3, CK20, CK5/6, and CK14 protein expression. The IHC-based subtypes in MIBC subtypes were classified as luminal (GATA3+ CK5/6−, 38.6%), basal (GATA3−CK5/6+, 12.9%), mixed (GATA3+ CK5/6+, 37.9%), and double-negative (GATA3−CK5/6−, 10.6%) in 132 MIBC patients. All individual markers and clinicopathological parameters were analyzed against treatment outcomes after radical cystectomy. The mean patient age was 65.6 years, and the male to female ratio was 6.8:1. Positive IHC expression of GATA3, CK20, CK5/6, and CK14 were 80.3%, 50.8%, 42.4%, and 28.0%, respectively. Only GATA3 and CK5/6 were significantly associated with survival outcome (p values = 0.004 and 0.02). The mixed subtype was significantly better in 5-year OS at 42.8%, whereas the double-negative subtype had the worst prognosis (5-year OS 7.14%). The double-negative subtype had a hazard ratio of 3.29 (95% CI 1.71–6.32). Subtyping using GATA3 and CK5/6 was applicable in MIBCs, and patients with the double-negative subtype were at the highest risk and may require more intensive therapy.

scholarly journals Long-Term Experience with Radiofrequency-Induced Hyperthermia Combined with Intravesical Chemotherapy for Non-Muscle Invasive Bladder Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 377
Author(s):  
Iris S. G. Brummelhuis ◽  
Yvonne Wimper ◽  
Hilde G. J. M. Witjes-van Os ◽  
Tom J. H. Arends ◽  
Antoine G. van der Heijden ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Complete Response ◽  
Intravesical Chemotherapy ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Durable Response ◽  
Induced Hyperthermia ◽  
Efficacy Analysis ◽  
Muscle Invasive

Background: The recurrence rate of non-muscle invasive bladder cancer (NMIBC) is high, despite intravesical treatments. Importantly, patients are frequently unfit or unwilling to undergo a recommended radical cystectomy when standard intravesical treatments fail, due to the substantial risk of morbidity and mortality. For these patients, radiofrequency-induced hyperthermia combined with intravesical chemotherapy (RF-CHT) has shown promising results. We aim to determine treatment outcomes and assess the effect of (ablative) dose. Methods: 299 intensively pretreated patients treated with RF-CHT were included in safety analysis. Of these, 274 patients who fulfilled induction treatments were included in efficacy analysis. Six-month complete response (CR) and durable response were reported for (concomitant) carcinoma in situ (CIS) patients and recurrence-free survival (RFS) for papillary patients. Results: For CIS, six-month CR-rate was 56.0%; and durable response rates were 79.7%, 66.5%, and 40.3% at one-, two- and five-year, respectively. RFS rates for papillary patients were 77.9%, 57.5%, and 37.2%, respectively. Patients treated with ablative dose are less likely to develop recurrence (adjusted Hazard Ratio 0.54, p = 0.01), compared to adjuvant dose. Conclusions: RF-CHT is effective in NMIBC patients in whom standard intravesical treatments have failed and should be considered in patients who are unwilling or unfit to undergo radical cystectomy. Patients with CIS or residual papillary tumor at baseline benefit from ablative dose.

Evaluating Patient-Defined Priorities for Female Patients with Bladder Cancer

2020 ◽  
pp. 1-8
Author(s):  
Amanda X. Vo ◽  
Mary Kate Keeter ◽  
Emily S. Tuchman ◽  
Joshua J. Meeks ◽  
Alicia K. Morgans
Keyword(s):  
Bladder Cancer ◽  
Locally Advanced ◽  
Invasive Bladder Cancer ◽  
Emotional Wellbeing ◽  
Structured Interviews ◽  
Muscle Invasive Bladder Cancer ◽  
Care Experience ◽  
Female Patients ◽  
Muscle Invasive ◽  
Optimal Approach

BACKGROUND: Although bladder cancer is much more common in men than in women, female patients with bladder cancer present with more locally advanced tumors and have worse disease-specific outcomes than male patients, even after controlling for biological differences. There is a paucity of research regarding the optimal approach to caring for female patients with bladder cancer in ways that maximize patient satisfaction, preferences, and values. OBJECTIVE: We sought to explore patient-defined priorities and areas in need of improvement for female patients with bladder cancer from the patient perspective. METHODS: We conducted focus group sessions and semi-structured interviews of women treated for bladder cancer to identify patient priorities and concerns until reaching topic saturation. Transcripts were analyzed thematically. RESULTS: Eight patients with muscle-invasive bladder cancer and six patients with non-muscle-invasive bladder cancer participated in two focus groups and seven interviews total. Three themes emerged as significantly affecting the care experience: physical impacts, mental health and emotional wellbeing, and the patient-provider interaction. Each theme included patient-defined specific recommendations on approaches to optimizing the care experience for women with bladder cancer. CONCLUSIONS: Although most participants were satisfied with the quality of care they received, they identified several opportunities for improvement. These concerns centered around enhancing support for patients’ physical and mental needs and strengthening the patient-provider interaction. Efforts to address these needs and reduce gender disparate outcomes via quality improvement initiatives are ongoing.

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