Treatment-free Survival Research Articles

Treatment-Free Remission (TFR) after Two Different Durations of Nilotinib Consolidation in Patients with Chronic Myeloid Leukemia (CML) Previously Treated with Imatinib: Enestpath Study Results

Treatment-Free Remission (TFR) after Two Different Durations of Nilotinib Consolidation in Patients with Chronic Myeloid Leukemia (CML) Previously Treated with Imatinib: Enestpath Study Results

Treatment-free survival over extended follow-up of patients with advanced melanoma treated with immune checkpoint inhibitors in CheckMate 067

BackgroundTreatment-free survival (TFS) characterizes disease control after discontinuation of immune checkpoint inhibitors (ICIs) until subsequent therapy or death. We previously evaluated TFS in a pooled analysis of the CheckMate 067...

Does Protocol Make a Difference? Comparison of Two Prostate Cancer Active Surveillance Cohorts: A Non–protocol-based Follow-up and a Protocol-based Contemporary Follow-up

BackgroundActive surveillance (AS) is the preferred option for initial management for low-risk prostate cancer (PC). Although many AS protocols exist, there is little evidence to support one over another. ObjectiveTo assess whether there is difference in overall (OS), prostate cancer–specific (CSS), metastasis-free (MFS), or treatment-free (TFS) survival between a strict (Prostate cancer Research International: Active Surveillance [PRIAS]) and a loose (European Randomized study of Screening for Prostate Cancer [ERSPC]) AS protocol. Design, setting, and participantsThis study included two cohorts of men (n = 518) with low-risk, localized, Gleason score ≤7 PC. The ERSPC cohort included 241 men followed for 9.5 yr (median) with a non–protocol-based follow-up. The PRIAS cohort included 277 men followed for 5 yr (median) with a strict protocol. Outcome measurements and statistical analysisOS, CSS, MFS, and TFS were compared by the Kaplan-Meier method, competing risk analysis, and Cox proportional hazard regression. Results and limitationsAs expected, due to the difference in median follow-up time between the cohorts, a difference in the absolute number of events was seen. However, no difference in any of the survival outcomes was evident in the Kaplan-Meier or competing risks analysis. Furthermore, in Cox proportional hazard regression analysis, cohort (ERSPC vs PRIAS) was not associated with any of the outcomes. Results are limited by the retrospective study design, limited statistical power, and inability to match the cohorts for predictive factors. ConclusionsThere was no difference in survival outcomes between a non–protocol-based follow-up and a protocol-based contemporary AS follow-up of patients with low-risk PC. However, a longer follow-up is needed. Patient summaryWe compared survival outcomes of two cohorts of patients with low-risk prostate cancer: a strict and a loose follow-up protocol. We found no differences in survival measures between the cohorts.

OUTCOMES OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) ACCORDING TO THE REASONS FOR INITIATION OF FIRST-LINE TREATMENT: A RETROSPECTIVE ANALYSIS OF THE BRAZILIAN REGISTRY OF CLL

To describe the outcomes of different reasons for initiating first-line treatment in a series of patients with CLL. Retrospective observational study with all patients with CLL in the Brazilian Registry of CLL(RBCLL), that was started in 2004. Between January 2004 and March 2021, a total of 1654 patients were followed at 30 centers. After a median follow-up of 86 months (range:3-315), there were 864 patients (52%) who were not treated, and 790 (48%) who were treated. Among the untreated patients, 636 (74%) did not have treatment indication while 228 (26%) had treatment indication but were not treated. These patients were not treated despite having an indication because of the following reasons:more conservative treatment indications in 59% of cases, death during follow up from unrelated causes in 15%, early death associated with poor clinical condition in 5% of cases, and for unknown reasons in 21%. Among 790 patients who were treated, the most common reasons for treatment initiation were cytopenias in 56%, and symptomatic lymphadenopathy in 26%. Other indications: disease-related constitutional symptoms in 22%, progressive lymphocytosis in 15%, symptomatic splenomegaly in 11%, and extranodal disease and steroid-refractory autoimmune complications in 1%, each. Besides,50 patients (7%) were treated although did not have a treatment indication. Treatment-free survival (TFS) was 37% at 8 years. It was only 10% for those with treatment indications due to cytopenias or lymphadenopathy, 25% for those with other treatment indications and 78% for those without indication (p < 0.0001). Median time between diagnosis and first-line treatment initiation was significantly shorter in patients with treatment indication due to cytopenias (7 months), and in those treated due to lymphadenopathy (13 months), than in those due to other reasons(37 months), and those without treatment indication (median not reached, p < 0.0001). Cytopenias as a reason for treatment initiation was associated with inferior TFS even among Binet A and B patients (median time 30 months vs. not reached). Analyzing the 375 patients who were treated due to cytopenias, anemia (hemoglobin<10 g/dL) was significantly associated with worse survival (27% vs. 55%, p < 0.0001), while thrombocytopenia (platelets<100x10 9 /L) had no impact on survival. Overall survival (OS) was 61% at 8 years among treated patients. OS was significantly worse in patients who were treated due to cytopenias (48%) than in those treated for other reasons (75%, p < 0.0001). Cytopenia as an indication of treatment was associated with inferior OS even among Binet A and B patients (79% vs. 63%, p = 0.002). Indeed, after correcting for age,Binet staging and renal function, cytopenias remained significantly associated with worse OS(hazard ratio–HR:2.98,95% confidence interval 1.26-7.06). Progressive lymphocytosis as a treatment indication was associated with a significantly better OS (73%vs.58%, p = 0.002), although the protective effect did not remain after a multivariate analysis. Median time-to-next treatment (TTNT) after first-line treatment was 40 months. Median TTNT was also significantly shorter for patients treated due to cytopenias (30 months) than for those treated due to lymphadenopathy (71 months), and due to other reasons (56 months, p < 0.0001). Cytopenias and lymphadenopathy were the most common reasons for treatment initiation. Cytopenias as a reason for treatment initiation was associated with inferior OS and TFS, as well as TTNT and should therefore be regarded as an independent risk factor for worse outcome in patients with CLL. These real-world data may help clinicians to choose wisely when and for whom to initiate therapy in CLL.

Factors Associated with Discontinuation of Active Surveillance among Men with Low-Risk Prostate Cancer: A Population-Based Study.

The purpose of this study was to describe the uptake, discontinuation and variation of active surveillance (AS) by provider and patient level characteristics. This observational, population-based study used linked administrative databases and pathology reports to identify all men diagnosed with Gleason score ≤6 prostate cancer (PC) between January 1, 2008 and December 31, 2014 in Ontario, Canada. The Cochran-Armitage test was used for AS trend over time. Treatment-free survival was estimated using cumulative incidence function. Factors associated with discontinuation of AS were evaluated using Cox proportional hazard models. Active surveillance was the initial management strategy for 8,541 cases (51%). Use of AS significantly increased from 38% in 2008 to 69% in 2014 (p=0.001). Men on AS were significantly older (64 years, SD 8.0) than those on initial treatment (62 years, SD 7.7; p=0.001). After a median followup of 48 months, 4,337 (51%) patients had discontinued AS. Treatment-free survival for AS patients at 1, 3, and 5 years were 85%, 58% and 52%, respectively. Median time to definitive treatment after initial AS was 16 months (IQR 11-25 months). Factors associated with AS discontinuation were younger age at diagnosis, year of diagnosis, higher comorbidities, treatment at academic center, treatment by physician and institution in the highest volume tertile, and adverse cancer-specific characteristics (higher prostate specific antigen [PSA], higher number of positive cores and higher percentage of core involvement at diagnosis). Although the uptake of AS significantly increased over time, there has been a relatively high rate of discontinuation over 5 years. Factors associated with transition to definitive treatment were younger age, care provided by higher volume physicians and institutions, higher PSA and greater PC volume at diagnosis. These results may help guide policy making, developing quality indicators, and developing targeted continued education for physician and patients embarking on AS to establish realistic expectations.

MP62-12 CONDITIONAL FREEDOM FROM PROGRESSION ON ACTIVE SURVEILLANCE OF PROSTATE CANCER STRATIFIED BY NCCN RISK

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance II (MP62)1 Sep 2021MP62-12 CONDITIONAL FREEDOM FROM PROGRESSION ON ACTIVE SURVEILLANCE OF PROSTATE CANCER STRATIFIED BY NCCN RISK Joshua Harvey, Andrew Gusev, Florian Rumpf, Keyan Salari, Jeffrey Twum-Ampofo, Matthew Wszolek, Douglas Dahl, Michael Blute, and Adam Feldman Joshua HarveyJoshua Harvey More articles by this author , Andrew GusevAndrew Gusev More articles by this author , Florian RumpfFlorian Rumpf More articles by this author , Keyan SalariKeyan Salari More articles by this author , Jeffrey Twum-AmpofoJeffrey Twum-Ampofo More articles by this author , Matthew WszolekMatthew Wszolek More articles by this author , Douglas DahlDouglas Dahl More articles by this author , Michael BluteMichael Blute More articles by this author , and Adam FeldmanAdam Feldman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002102.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Active surveillance (AS) is an accepted strategy for men with very low, low, and select cases of favorable intermediate National Comprehensive Cancer Network (NCCN) risk prostate cancer (PCa). However it is not well defined how the risk of progression evolves during AS. Conditional survival measures the probability a patient will continue to survive some number of years, given that they have already survived a certain number without progression. We evaluated our AS cohort to investigate overall and conditional progression free survival on AS, stratified by the NCCN risk groups. METHODS: We reviewed our institutional database of 1252 men enrolled in AS for localized PCa from 1996-2016. Overall freedom from pathologic grade progression on follow-up biopsy and treatment free survival were estimated using the Kaplan-Meier method. Survival curves were compared pairwise using the Log-rank test and adjusted for false discovery rates with the Benjamini-Hochberg procedure. Three-year conditional survival estimates were derived for both outcomes from the Kaplan-Meier estimator. RESULTS: Of 1252 men, 521 (41.6%) met criteria for very low, 606 (48.4%) for low, and 125 (10.0%) for favorable intermediate NCCN risk at diagnosis. Median follow-up time was 6.5 years (IQR 4.1-9.4). Median pathologic grade progression free survival in years was significantly longer for very low risk (7.8, 95% CI 6.8-11.2) compared to low risk men (5.6, 95% CI 4.7-6.9), however neither was significantly different from favorable intermediate risk men (5.9). There was no significant difference in treatment free survival between the three risk groups. At diagnosis, the three-year risk for pathologic grade progression (24%, 95% CI 21-27%) and progression to treatment (22%, 95% CI 20-25%) were similar. However, with increasing time of event-free AS, the conditional probability of pathologic grade progression increased, while that of progression to treatment decreased. CONCLUSIONS: Our results demonstrate that despite a mild increase in pathologic progression free survival in very low risk men, there was no clear difference in overall treatment free survival between very low, low, and select favorable intermediate NCCN risk men. Further, with increased time spent on AS, despite elevated rates of pathologic progression, patient progression to treatment decreased. This trend may be indicative of changes in goals of care as men with PCa age and should be closely monitored during AS. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1096-e1097 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Harvey More articles by this author Andrew Gusev More articles by this author Florian Rumpf More articles by this author Keyan Salari More articles by this author Jeffrey Twum-Ampofo More articles by this author Matthew Wszolek More articles by this author Douglas Dahl More articles by this author Michael Blute More articles by this author Adam Feldman More articles by this author Expand All Advertisement Loading ...

PD17-08 IMPACT OF SERIAL PROSTATE MULTIPARAMETRIC MRI ON TREATMENT FREE SURVIVAL IN MEN ON ACTIVE SURVEILLANCE

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I (PD17)1 Sep 2021PD17-08 IMPACT OF SERIAL PROSTATE MULTIPARAMETRIC MRI ON TREATMENT FREE SURVIVAL IN MEN ON ACTIVE SURVEILLANCE Joshua Harvey, Andrew Gusev, Jeffrey Twum-Ampofo, Alberto Pieretti, Florian Rumpf, Alice Yu, Keyan Salari, Douglas Dahl, and Adam Feldman Joshua HarveyJoshua Harvey More articles by this author , Andrew GusevAndrew Gusev More articles by this author , Jeffrey Twum-AmpofoJeffrey Twum-Ampofo More articles by this author , Alberto PierettiAlberto Pieretti More articles by this author , Florian RumpfFlorian Rumpf More articles by this author , Alice YuAlice Yu More articles by this author , Keyan SalariKeyan Salari More articles by this author , Douglas DahlDouglas Dahl More articles by this author , and Adam FeldmanAdam Feldman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001999.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate multiparametric magnetic resonance imaging (mpMRI) is increasingly utilized in the risk stratification of men with prostate cancer (PCa). During Active Surveillance (AS) men often receive multiple mpMRIs, yet how the findings impact their cancer outcomes is not well described. We investigated our AS cohort to assess the outcomes of men who underwent at least two prostate mpMRIs during AS METHODS: We reviewed our institutional database of 1252 men enrolled in AS for localized PCa from 1996-2016. We identified 205 men who underwent at least two prostate mpMRIs during AS. MRIs without a reported Prostate Imaging Reporting and Data System (PIRADS) version 2.0 score were excluded. Radiologic progression was defined as new lesion (PIRADS ≥ 3) on a previously negative MRI or increase in PIRADS score of a previous lesion. Multivariate logistic regression was used to evaluate if PIRADS score from serial MRI was a predictor of progression to treatment on AS. Covariates adjusted for included age, NCCN risk group, PSA density, and PIRADS score on initial MRI. A Cox proportional hazards model with PIRADS scores as time-dependent variables was used to evaluate the impact of each PIRADS score during AS on patient treatment free survival (TFS). Survival analyses were conducted using the Kaplan-Meier method. RESULTS: Median values for the cohort of 205 men were as follows: number of MRIs meeting criteria: 2 (range 2-3); follow up time: 5.1 years (IQR 3.7-7.7); time between MRIs: 2 years (IQR 1.5-2.8). On MRI 1, 10% of patients had PIRADS 3 lesions, 19% PIRADS 4, 6% PIRADS 5, while 65% were negative. On repeat MRI, 62% of PIRADS scores did not change, while 27% increased and 11% decreased. Compared to lesions that remained the same, PIRADS increase was an independent predictor of progression to treatment (OR 9.0, 95% CI 3.8-21.4, p<0.001). PIRADS decrease was not a significant predictor of outcomes, yet a negative result on repeat MRI was an independent predictor of reduced progression to treatment (OR 0.16, 95% CI 0.07-0.37, p<0.001). Overall, men with negative MRIs on AS experienced prolonged TFS compared to those with PIRADS 5 lesions, with 85% vs 48% remaining on surveillance at 5 years, respectively. CONCLUSIONS: While a majority of men did not experience PIRADS score change on serial prostate mpMRI, radiologic progression was an independent predictor of increased AS failure and progression to treatment. Men with serial negative MRIs on AS have significantly prolonged TFS and may be candidates for an increased interval between surveillance MRI and biopsy. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e287-e288 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Harvey More articles by this author Andrew Gusev More articles by this author Jeffrey Twum-Ampofo More articles by this author Alberto Pieretti More articles by this author Florian Rumpf More articles by this author Alice Yu More articles by this author Keyan Salari More articles by this author Douglas Dahl More articles by this author Adam Feldman More articles by this author Expand All Advertisement Loading ...

MP46-10 FOCAL CRYOTHERAPY FOR LOW- TO INTERMEDIATE-RISK PROSTATE CANCER: LONG TERM RESULTS AND MATCHED PAIR COMPARISON WITH ACTIVE SURVEILLANCE

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy (MP46)1 Sep 2021MP46-10 FOCAL CRYOTHERAPY FOR LOW- TO INTERMEDIATE-RISK PROSTATE CANCER: LONG TERM RESULTS AND MATCHED PAIR COMPARISON WITH ACTIVE SURVEILLANCE Giancarlo Marra, Timo Soeterik, Davide Oreggia, Caio Pasquali, Rafael Tourinho-Barbosa, Marco Moschini, Claudia Filippini, Harm H. E. van Melick, Roderick C. N. van den Bergh, Paolo Gontero, Nathalie Cathala, Petr Macek, Rafael Sanchez-Salas, and Xavier Cathelineau Giancarlo MarraGiancarlo Marra More articles by this author , Timo SoeterikTimo Soeterik More articles by this author , Davide OreggiaDavide Oreggia More articles by this author , Caio PasqualiCaio Pasquali More articles by this author , Rafael Tourinho-BarbosaRafael Tourinho-Barbosa More articles by this author , Marco MoschiniMarco Moschini More articles by this author , Claudia FilippiniClaudia Filippini More articles by this author , Harm H. E. van MelickHarm H. E. van Melick More articles by this author , Roderick C. N. van den BerghRoderick C. N. van den Bergh More articles by this author , Paolo GonteroPaolo Gontero More articles by this author , Nathalie CathalaNathalie Cathala More articles by this author , Petr MacekPetr Macek More articles by this author , Rafael Sanchez-SalasRafael Sanchez-Salas More articles by this author , and Xavier CathelineauXavier Cathelineau More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002067.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Only one randomized controlled trial details the comparison of focal therapy and active surveillance (AS) for low-risk prostate cancer (PCa). Long term outcomes of focal cryotherapy (FC) have not been detailed. Our aim is thus to evaluate long-term results of FC and to compare them with AS. METHODS: Two prospective series of 121 (FC) and 459 (AS) consecutive patients (2008-2018) were included, comprising men diagnosed with low- to intermediate-risk PCa. Primary outcome included Radical or androgen deprivation (ADT) free-survival (FS). Secondary outcomes were any treatment-free survival (FS); metastases and overall-FS (OS). To decrease confounding factors, a matched pair analysis was performed using seven co-variates. RESULTS: In the FC cohort 76% of patients had ISUP 1. No relevant differences were present amongst matched variables except for cT stage (p<0.01) and year of entry (p<0.01). Median follow-up of the FC cohort was 85-mo (IQR 58-104). At ten-years, FC radical or ADT-free, any treatment-free, metastasis-free and OS were 51%, 40%, 94% and 97%. No differences were noted with AS After matching (all p>0.05), with the exception of radical or ADT treatment-FS, higher for FC (AS 10-years 39.3%; p=0.04 – Figure 1). Time to radical, to radical and ADT and to any treatment were all shorter for AS (all p<0.01). Complications were experienced by 26.5% of the FC cohort with Clavien >2 being rare (n=3). Continence changes were minimal (p=0.08) whilst both IIEF-5 and IPSS scores increased at 18 months from FC (p=0.03 and p=0.02). CONCLUSIONS: When performed in the context of mainly low-risk PCa FC is safe and, compared to AS it increases time to radical therapy. However FC does not provide strong oncological advantages at an early long-term follow-up. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e817-e817 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giancarlo Marra More articles by this author Timo Soeterik More articles by this author Davide Oreggia More articles by this author Caio Pasquali More articles by this author Rafael Tourinho-Barbosa More articles by this author Marco Moschini More articles by this author Claudia Filippini More articles by this author Harm H. E. van Melick More articles by this author Roderick C. N. van den Bergh More articles by this author Paolo Gontero More articles by this author Nathalie Cathala More articles by this author Petr Macek More articles by this author Rafael Sanchez-Salas More articles by this author Xavier Cathelineau More articles by this author Expand All Advertisement Loading ...

MP46-11 HIGH INTENSITY FOCUSED ULTRASOUND (HIFU) VS RADICAL PROSTATECTOMY (RP) IN THE CURATIVE TREATMENT OF ISUP 1-2 LOCALIZED PROSTATE CANCER: ONCOLOGICAL INTERMEDIATE RESULTS OF THE HIFI STUDY

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy (MP46)1 Sep 2021MP46-11 HIGH INTENSITY FOCUSED ULTRASOUND (HIFU) VS RADICAL PROSTATECTOMY (RP) IN THE CURATIVE TREATMENT OF ISUP 1-2 LOCALIZED PROSTATE CANCER: ONCOLOGICAL INTERMEDIATE RESULTS OF THE HIFI STUDY Pascal Rischmann, Bob Occean, Thierry Chevallier, Xavier Rebillard, Arnaud Villers, Nadine Houede, and Patrick Coloby Pascal RischmannPascal Rischmann More articles by this author , Bob OcceanBob Occean More articles by this author , Thierry ChevallierThierry Chevallier More articles by this author , Xavier RebillardXavier Rebillard More articles by this author , Arnaud VillersArnaud Villers More articles by this author , Nadine HouedeNadine Houede More articles by this author , and Patrick ColobyPatrick Coloby More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002067.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although HIFU treatment showed promising oncological results in several retrospective studies, large and comparative prospective studies are yet missing. The HiFi study (NCT 04307056) compares HIFU (total or subtotal) vs radical prostatectomy (RP) as a first line treatment in ISUP1 (not eligible for active surveillance) and ISUP2 grade groups localized prostate cancer. The objective of this prospective open-label comparative multicenter study was to evaluate oncological efficacy, functional results and safety. We report here intermediate oncological results at 24-months. METHODS: Inclusion criteria were low or intermediate risk PCa (PSA<15 ng/ml, GS≤3+4 and clinical stage T1-2 NxM0), and a maximum of 4 sextants invaded out of 6, mpMRI. A minimum age of 70 years for HIFU patients (current French guidelines) and a life expectancy of 10 years for the RP patients. HIFU treatment (Focal One®, Edap tms, Vaux-en-Velin) was considered with at least 70% of the gland treated. This study was conducted under IRB and ethic committee approval. Main objective was to compare salvage treatment-free survival (STFS) in both arms. Patients were followed-up for 30-months. RESULTS: From April 2015 to September 2019, 3364 patients (HIFU: 1988, RP: 1376) were prospectively included in 42 French centers. Median age was 74.6 vs 65 years, median PSA was 7.1 vs 6.9 (p=0.4). 59% of the patients were ISUP2 in the HIFU arm vs 63% in the RP arm. At 24-months the STFS was significantly higher in the HIFU arm (97.5%) compared with RP (90.3%) with a risk of experiencing salvage treatment 2.5 times higher after RP (HR: 0.4, 95% CI [0.16-0.34], p<0.01). In the HIFU arm, the positive biopsy rate was 8.6%; in the RP arm, positive margins were 24.7%. CONCLUSIONS: These intermediate results do not yet allow a fair comparison of the two arms due to the specific profile of each group. Indeed, following early positive margin results in RP arm, salvage radiotherapy is probably initiated earlier. The follow-up of oncological data up to 30 months, scheduled in the study, is justified. Source of Funding: Sponsor: French Urological AssociationFunding: Innovation Package (French Ministry of Health) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e817-e817 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pascal Rischmann More articles by this author Bob Occean More articles by this author Thierry Chevallier More articles by this author Xavier Rebillard More articles by this author Arnaud Villers More articles by this author Nadine Houede More articles by this author Patrick Coloby More articles by this author Expand All Advertisement Loading ...

Prostate cancer active surveillance outcomes in a cohort composed primarily of African American and Hispanic American Men

IntroductionActive surveillance outcomes in minority patients are poorly characterized, as most surveillance series are comprised primarily of Caucasian men. We aimed to characterize outcomes of African American and Hispanic men undergoing surveillance and to identify factors associated with transition to definitive treatment. Material and MethodsWe performed a retrospective analysis of men undergoing active surveillance at our institution. Reasons for transition to definitive treatment were determined. Cessation of active surveillance was recommended for Gleason upgrading on surveillance biopsy. We characterized treatment-free survival for men on surveillance and compared this by race/ethnicity (as self reported by patients). Demographic and clinical variables associated with active surveillance cessation were identified using Cox proportional hazards regression. ResultsA total of 141 men were on active surveillance: 84 non-Hispanic Black/African American (59.6%), 32 Hispanic (22.7%), and 25 non-Hispanic White/Caucasian (17.7%). Two-year treatment-free survival for Caucasian, Black and Hispanic patients was 81.2%, 54.4%, and 75.0%, respectively. Pairwise Cox proportional hazards analysis showed significantly decreased treatment-free survival in Black compared to Caucasian men (HR 2.42, 95% CI 1.03–5.68). In African American men, cessation of active surveillance occurred most commonly due to grade reclassification at the time of confirmatory biopsy. ConclusionsAmong our active surveillance cohort composed primarily of racial and ethnic minorities, we identified relatively high rates of progression to definitive treatment. African American race was associated with surveillance cessation on univariate analysis. These findings stress the importance of confirmatory biopsy and strict compliance with surveillance protocols in AA men to ensure timely detection of disease reclassification.

A Neoantigen-Based Peptide Vaccine for Patients With Advanced Pancreatic Cancer Refractory to Standard Treatment.

BackgroundNeoantigens are critical targets to elicit robust antitumor T-cell responses. Personalized cancer vaccines developed based on neoantigens have shown promising results by prolonging cancer patients’ overall survival (OS) for several cancer types. However, the safety and efficacy of these vaccine modalities remains unclear in pancreatic cancer patients.MethodsThis retrospective study enrolled 7 advanced pancreatic cancer patients. Up to 20 neoantigen peptides per patient identified by our in-house pipeline iNeo-Suite were selected, manufactured and administered to these patients with low tumor mutation burden (TMB) (less than 10 mutations/Mb). Each patient received multiple doses of vaccine depending on the progression of the disease. Peripheral blood samples of each patient were collected pre- and post-vaccination for the analysis of the immunogenicity of iNeo-Vac-P01 through ELISpot assay and flow cytometry.ResultsNo severe vaccine-related adverse effects were witnessed in patients enrolled in this study. The mean OS, OS associated with vaccine treatment and progression free survival (PFS) were reported to be 24.1, 8.3 and 3.1 months, respectively. Higher peripheral IFN-γ titer and CD4+ or CD8+ effector memory T cells count post vaccination were found in patients with relatively long overall survival. Remarkably, for patient P01 who had a 21-month OS associated with vaccine treatment, the abundance of antigen-specific TCR clone drastically increased from 0% to nearly 100%, indicating the potential of iNeo-Vac-P01 in inducing the activation of a specific subset of T cells to kill cancer cells.ConclusionsNeoantigen identification and selection were successfully applied to advanced pancreatic cancer patients with low TMB. As one of the earliest studies that addressed an issue in treating pancreatic cancer with personalized vaccines, it has been demonstrated that iNeo-Vac-P01, a personalized neoantigen-based peptide vaccine, could improve the currently limited clinical efficacy of pancreatic cancer.Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT03645148).Registered August 24, 2018 - Retrospectively registered

Impact of BCR-ABL1 Transcript Type on Response, Treatment-Free Remission Rate and Survival in Chronic Myeloid Leukemia Patients Treated with Imatinib.

The most frequent BCR-ABL1-p210 transcripts in chronic myeloid leukemia (CML) are e14a2 and e13a2. Imatinib (IM) is the most common first-line tyrosine–kinase inhibitor (TKI) used to treat CML. Some studies suggest that BCR-ABL1 transcript types confer different responses to IM. The objective of this study was to correlate the expression of e14a2 or e13a2 to clinical characteristics, cumulative cytogenetic and molecular responses to IM, acquisition of deep molecular response (DMR) and its duration (sDMR), progression rate (CIP), overall survival (OS), and treatment-free remission (TFR) rate. We studied 202 CML patients, 76 expressing the e13a2 and 126 the e14a2, and correlated the differential transcript expression with the above-mentioned parameters. There were no differences in the cumulative incidence of cytogenetic responses nor in the acquisition of DMR and sDMR between the two groups, but the e14a2 transcript had a positive impact on molecular response during the first 6 months, whereas the e13a2 was associated with improved long-term OS. No correlation was observed between the transcript type and TFR rate.

Mutations In XPO1, POT1, BIRC3 and FBXW7 collectively Predict Poor Outcome At Diagnosis In CLL and MBL Independent From The SF3B1 and NOTCH1 Status

With the application of high-throughput sequencing, our understanding of the somatic mutations that contribute to the pathogenesis of CLL has expanded significantly. Amongst these mutations, NOTCH1 and SF3B1 are the most prevalent and at diagnosis are associated with reduced survival independent of clinical and biological variables. However, we have limited understanding of the prognostic impact of other, less prevalent mutations. To address this question, we investigated the distribution, clinical significance and clonal acquisition of SF3B1, NOTCH1, XPO1, POT1, BIRC3, MYD88 and FBXW7 mutations in a single-centre diagnostic cohort of 140 patients with CLL, of whom 115 had Binet stage A disease and 91 patients with clinical MBL based on the 2008 IWCLL/NCI diagnostic criteria. Ninety patients (35 MBL and 55 CLL) also had DNA samples analyzed at a second time point (median 72 months, 24-145 months from diagnosis). We defined progressive disease as either presentation with stage B/C disease, evolution of MBL or stage A to stage B/C and/or the need for treatment. With high-resolution melt (HRM) analysis and subsequent Sanger sequencing, we identified mutations of SF3B1 in 9% (21/225), NOTCH1 in 5% (12/228), POT1 in 6 %(7/123), XPO1 in 2 %(4/196), MYD88 in 1% (3/223) and BIRC3 mutations in 0.5 % (1/222) of patients. FBXW7 mutations were identified in 8% (3/36) of the trisomy 12 patients from our cohort. In the patients studied sequentially we confirmed acquired mutations of SF3B1 (n=5) and XPO1 (n=1) in 3 patients with MBL and in 3 with CLL. Whilst we confirmed the impact of NOTCH1 mutations on treatment free survival (76 vs. 107 months, p=0.002) and SF3B1 mutations on overall survival (96 vs. 117 months, p=0.004), the prevalence of mutations in the other genes was too low to assess individually. We therefore assessed the collective burden of mutations in our cohort (excluding the MYD88 cases which had long term stable disease ) and demonstrated the following: 1) In both the MBL and CLL cohorts, the frequency of a gene mutation was higher in patients with progressive disease than in those with long-term, clinically stable disease (MBL: 36 vs. 12% p=0.02, CLL: 41 vs. 10%, p<0.001),and also independent of SF3B1 and NOTCH1 mutations and deletions of 17p (MBL and CLL: 11 vs. 3%; p=0.031). 2) All patients and those in the MBL cohort, with mutations targeting genes other than SF3B1 and NOTCH1 were more likely to require treatment (Entire cohort: OR 3.1, p=0.008, MBL cohort: OR 20, p= 0.006). This resulted in a reduced treatment-free survival (Entire cohort: 40 vs. 102 months, HR 10, 95%CI 3-30, p<0.001) and overall survival. (Entire cohort: 97 vs. 120 months HR 2.7, 95% CI 1.2-5.9, p=0.013) which was independent of the presence of a 17p deletion (p=0.008) and of IGHV status in bivariate analysis (p=0.02). 4/6 patients who acquired a mutation at 38-208 months (median 127 months) after initial analysis required treatment. Taken together, our study suggests that identifying mutations in genes other than NOTCH1 and SF3B1 may have utility in the clinical management of MBL and CLL as they predict for progressive disease, treatment requirement and reduced survival. Much larger studies with sequential data post therapy will be required to elucidate whether specific rare gene mutations predict a poor outcome or whether they either result in, or are a marker of genomic instability and subsequent genomic complexity.Frequencies of mutations and cytogenetic aberrationsMBL stable (n=34)MBL evolving to stage A CLL (n=29)MBL progressive (n=22)Binet A CLL stable (n=70)Binet A CLL progressive (n=45)Binet B CLL (n=20)NOTCH1 (%)0/340/293/22 (14)1/69 (1.4)4/43 (9.3)1/19 (5)SF3B1 (%)1/34 (2.9)4/29 (14)2/22 (9)3/69 (4.3)11/45 (24)5/20 (25)total including all other screened genes (%)1/34 (2.9)4/29 (14)8/22 (36)7/70 (10)18/45 (40)7/20 (35)11q23 (%)1/34 (2.9)1/27 (3.7)2/20 (10)1/66 (1.5)9/40 (23)3/16 (19)17p (%)1/32 (3.1)1/27 (3.7)1/19 (5)2/66 (3)0/400/16IGHV unmutated/mutated (% / %)5/29 (15/85)5/24 (17/83)15/7 (68/32)10/60 (14/86)25/20 (66/44)18/2 (90/10)tri12 (%)7/24 (29)5/22 (23)7/18 (32)9/57 (16)10/39 (26)8/16 (50)biallelic del13q14 (%)9/21 (43)4/14 (29)2/11 (9)20/40 (50)6/19 (32)2/12 (17) Disclosures:No relevant conflicts of interest to declare.

Abnormal Karyotype (Not Only Complex) at Diagnosis Is an Independent Prognostic Factor for Overall Survival in Early Stage Chronic Lymphocytic Leukemia Patients. Results of a Prospective Study with a Median Follow-up of More Than 7-Years

Introduction: Only few studies have prospectively dealt with the prognostic impact on survival of both clinical and laboratory abnormalities in patients with early stage chronic lymphocytic leukemia (CLL) at diagnosis. In our previously published analyses including a prospective cohort of 307 CLL (Oliveira et al, Leuk Lymphoma. 2011; 52:429-35, Oliveira et al, Ann Hematol. 2015; 94:627-32), patients with atypical lymphocyte morphology, 11q deletion, and elevated beta-2 microglobulin had a shorter progression-free survival (PFS) and treatment-free survival (TFS). Abnormal karyotype (AK), 1 or more abnormalities at diagnosis, was not an independent prognostic factor at that time. Complex karyotype (CK), 3 or more abnormalities, despite having been described as an important prognostic marker in retrospective studies, was a rare finding at diagnosis in early stage CLL patients. The aim of this study is to evaluate prognostic factors at diagnosis in patients with early stage CLL for PFS, TFS and also OS, with a longer follow-up.Patients and methods: 307 patients were prospectively enrolled in the study from 2003 to 2010 in a single center. All clinical and laboratory data were homogeneously collected at diagnosis. Analysis of prognostic factors for survival was performed in 231 patients presenting early stage disease: lymphocytosis without other signs or symptoms of CLL (CLL Rai 0 and monoclonal B lymphocytosis, MBL). Survival curves were plotted using Kaplan-Meier's method and log-rank test was used to identify differences in survival between subgroups. Multivariate analysis was performed with Cox regression model. Variables included in the univariate analysis were: age, gender, LDH, beta-2 microglobulin, lymphocyte morphology, CD38, ZAP-70, deletions of 13q, 11q and 17p, trisomy 12, normal FISH and AK. The significant variables in the univariate analysis were included in the multivariate regression model.Results: Eighty-one patients had MBL and 150 were diagnosed with CLL Rai 0, 145 (62.8%) patients were male with a median age at diagnosis of 68 years (limits 27-93). One hundred sixteen patients presented a normal karyotype at diagnosis, 54 (23.3%) an AK [7 (3%) of them a CK], in 9 (3.9%) patients no metaphases were obtained for karyotype analysis and in 52 (22.5%) karyotype was not performed. With a median follow-up of 7.8 yrs (range 0.7-13.6), 37 (16%) patients died, 73 (31.6%) presented CLL progression and 60 (26%) required treatment. OS was 84%. AK was an independent prognostic factor for OS (OR 2.2, 95%CI: 1.0-4.6, p=0.038), TFS (OR 2.9, 95%CI: 1.4-6.0, p=0.003), and PFS (OR 2.4, 95%CI: 1.3-4.6, p=0.005). Atypical lymphocyte morphology was also an independent prognostic factor for OS (OR 2.7, 95%CI: 1.3-5.8, p=0.008) and elevated beta-2 microglobulin for PFS (OR 2.1, 95%CI:1.1-3.9, p=0.018).Conclusions: Abnormal karyotype (not only complex) at diagnosis in early stage CLL (CLL Rai 0 or MBL), is an independent prognostic factor for OS, PFS and TFS. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Duration of MRD-Negative Status in Multiple Myeloma (MM) Patients after Auto-HSCT Is a Criterion for Prolonged Remission without Maintenance Therapy

Background:Achievement of MRD-negative status in MM patients following auto-HSCT is a prognostic factor that has a positive effect on relapse-free survival (RFS). However, the time after which the loss of MRD-negative status occurs have not been established so far. The duration of MRD-negative status can be expected to allow determination of the necessity and duration of maintenance therapy (MT) received by MM patients who have achieved a stringent complete remission (CR) following auto-HSCT.Aims: To evaluate the duration of MRD-negative status achieved in MM patients following auto-HSCT; to assess the effects of MRD-negative status achievement on RFS and treatment-free survival (TFS).Patients and Methods: From March 2014 to October 2016, 29 patients with MM (12 males and 17 females) aged 40 to 66 years (median 56 years) who had achieved CR, following auto-HSCT, were enrolled in this prospective study. Disease stages (ISS) were as follows: stage I, II and III were observed in 9, 11 and 9 patients, respectively. Induction of remission included bortezomib-containing regimens (VCD, PAD) in all 29 patients. Immunomodulatory drugs and bendamustine were each used twice. Distribution of patients by type of anti-tumor responses (IMWG) after induction was as follows: CR, very good partial remission and partial remission were observed in 16 (55%), 12 (41%) and 1 (4%) patients, respectively. Single and tandem auto-HSCT were conducted in 25 and 4 patients, respectively. In order to determine MRD status, bone marrow examination using a six-color flow cytometric assay was performed on Day 100 following auto-HSCT with the use of an antibody panel to the following antigens: CD38, CD138, CD45, CD56, CD117, CD19. MRD-negative status was defined as presence of less than 20 clonal plasmatic cells among 2,000,000 white blood cells (<0.001%, detection limit - 10-5).After auto-HSCT, all patients were followed up and received no MT. The analysis of MRD status was conducted every 3 months until the development of a disease relapse with the use of a six-color flow cytometric assay. The follow-up period since the moment of MRD detection on Day 100 following auto-HSCT was 3 to 33 months (median value = 12 months). The evaluated parameters included the time to loss of MRD-negative status (period since the moment of detection of MRD-negative status on Day 100 following auto-HSCT till the appearance of minimal residual population), RFS (period since the moment of detection of MRD-status on Day 100 following auto-HSCT till the assertion of a disease relapse according to IMWG 2014 criteria), TFS (period since the moment of detection of MRD-negative status on Day 100 following auto-HSCT till the initiation of the next line of therapy). Statistical analysis was done using SAS 9.4. The compared groups were overall balanced for known significant factors.Results: Following auto-HSCT, stringent CR was achieved in 21 (72%) patients, while MRD-positive status was detected in 8 (28%) cases. Loss of MRD-negative status was ascertained in 7 (33%) out of 21 patients during the period from 3 to 13 months. MRD positive free survival was 60% within 33 months (Fig. 1).Immunochemical disease relapse was established in 3 (15%) patients with MRD-negative status and 5 (63%) patients with MRD-positive status achieved after auto-HSCT. Two-year RFS in patients with MRD-positive status was significantly lower compared to the patients with MRD-negative status: 25% vs. 80% (log-rank test, p=0.05, hazard ratio = 2.5, 95% CI = 0.9-6.4) (Fig. 2).TFS was significantly higher in patients with MRD-negative status achieved after auto-HSCT: 90% versus 20% within 28 months (p=0.03). It should be noted that only one patient from MRD-negative group required the initiation of the next line of therapy throughout the entire follow-up period as compared to 5 (63%) patients in MRD-positive group (Fig. 3).Conclusion: The values of time to loss of MRD-negative status in MM patients following auto-HSCT, which were determined in the study, confirmed the hypothesis of favorable prognosis without the use of MT. Prescription of additional treatment to patients who have achieved a stringent complete remission after auto-HSCT does not have any pathogenetical basis, is related to the risk of adverse events and requires the use of concomitant therapy. High values of RFS and TFS rates observed in patients with MRD-negative status following auto-HSCT also confirm our hypothesis. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Obinutuzumab (Gazyva) and High-Dose Methylprednisolone (HDMP) Combination for Patients with Chronic Lymphocytic Leukemia (CLL) - a Phase Ib/II Study

Obinutuzumab (Gazyva) and High-Dose Methylprednisolone (HDMP) Combination for Patients with Chronic Lymphocytic Leukemia (CLL) - a Phase Ib/II Study

Rituximab Maintenance for Two Years in Previously Untreated Follicular Lymphoma: No Difference in Outcome between Patients Receiving Treatment at Two Month Versus Three Month Interval

Rituximab maintenance (MR) improves progression free survival (PFS) in patients with follicular lymphoma after induction treatment. The PRIMA trial demonstrated a PFS benefit using a maintenance protocol in which rituximab was administered every 2 months in previously untreated follicular lymphoma (Salles et al, Lancet 2011). The EORTC 20981 trial showed a similar benefit in relapsed or refractory follicular lymphoma using a schedule in which rituximab was administered every 3 months (Van Oers et al. JCO 2010). These maintenance protocols have not been formally compared. This multi-center retrospective study compares the clinical outcome of patients with previously untreated follicular lymphoma receiving MR at 3 month intervals versus 2 month intervals.A total of 112 patients completed MR for follicular lymphoma after first line induction between 2005 and 2015: 71 (63%) received MR at 3 month interval and 41 (37%) at a 2 month interval. The GELF criteria (Brice et als, JCO, 1997) were met in 41 (59%) patients in the 3 month interval group and in 33 (79%) patients in the 2 month interval group. All patients received an induction regimen containing rituximab and 78% received R-CVP. Median follow up time was 59 months and was significantly longer in the 3 month interval group with 70 months compared to 40 months in the 2 month interval group (p < 0.001). Before the publication of PRIMA, most patients with previously untreated follicular lymphoma received MR at a 3 month interval which explains the longer follow up in this group. Progression was documented in 14 (20%) of the patients in the 3 month interval group and in 11 (26%) in the 2 month interval group. PFS at 40 months was similar in both groups with 88% in the 3 month interval group and 80% in the 2 month interval group (HR 0.454, 95% CI: 0.202 - 1.021, p 0.056). Twelve (17%) of the patients in the 3 month interval group and 8 (19%) in the 2 month interval group required second line therapy. Time to next treatment was not reached in either group. Treatment free survival at 40 months was similar between the two groups with 91% in the 3 month interval group compared to 80% in the 2 month interval group (HR 0.487, 95% CI: 0.193 - 1.230, p 0.128). Six (9%) of the patients in the 3 month interval group died, 4 (6%) of these deaths were attributed to the lymphoma, and 1 (2%) patient died in the 2 month interval group. Overall survival at 40 months was not statistically different between the 3 and 2 month interval groups with 96% and 100% respectively (HR 1.761, 95% CI: 0.194 - 15.982, p 0.615).The administration of MR at an interval of 3 months compared to 2 months does not seem to adversely affect the survival outcomes of patients with previously untreated follicular lymphoma. The administration of rituximab every 3 months instead of every 2 months would decrease the cost and potentially the infectious complications of MR. Although this study has limitations, such as a limited number of patients and a disparity between the two groups regarding the presence of GELF criteria, it provides preliminary data supporting the interest of further investigation of the administration of MR every 3 months in previously untreated follicular lymphoma. DisclosuresFleury:Amgen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Doucet:Abbvie: Consultancy; Roche: Consultancy; Janssen: Consultancy, Other: Speaker; Lundbeck: Consultancy; Celgene: Consultancy; Gilead: Consultancy.

“Duration of Deep Molecular Response” Has Most Impact on the Success of Cessation of Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia - Results from the EURO-SKI Trial

“Duration of Deep Molecular Response” Has Most Impact on the Success of Cessation of Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia - Results from the EURO-SKI Trial

Pembrolizumab for the treatment of renal cell carcinoma

ABSTRACT Introduction The acquisition of resistance to VEGF-inhibiting therapies has prompted research toward immunotherapy for the treatment of metastatic renal cell carcinoma (mRCC). Among several, checkpoint inhibitors including PD-1 and PD-L1 inhibitors are the most promising approach. Areas covered This review addresses the clinical efficacy of the anti-PD-1 monoclonal antibody pembrolizumab in first- and second-line treatment for mRCC regarding the most recent and significant published and ongoing studies. Attention is also given to its pharmacological characteristics as well as adverse events and its impact on patients’ quality of life. Expert opinion Immunotherapy has become the backbone for the treatment of advanced RCC. With the approval of several therapeutic options, research needs now to focus on defining the appropriate therapy for each patient. Axitinib plus pembrolizumab belongs to the combinations of tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors for the first-line treatment of metastatic RCC. New combinations of pembrolizumab plus TKI for the evaluation in first- and second-line treatment of mRCC available. However, studies directly comparing the various treatment regimens using predictive biomarkers and long-term endpoints, including treatment-free survival, are lacking.

Laterally Extended Endopelvic Resection Versus Chemo or Targeted Therapy Alone for Pelvic Sidewall Recurrence of Cervical Cancer

BackgroundLaterally extended endopelvic resection (LEER) has been introduced for treatment of pelvic sidewall recurrence of cervical cancer (PSRCC), which occurs in only 8% of patients with relapsed cervical cancer. LEER can only be performed by a proficient surgeon due to the high risk of surgical morbidity and mortality, but there is no evidence as to whether LEER is may be more effective than chemo or targeted therapy alone for PSRCC. Thus, we aimed to compare the efficacy and safety between LEER and chemo or targeted therapy alone for treatment of PSRCC.MethodsWe prospectively recruited patients with PSRCC who underwent LEER between December 2016 and December 2019. Moreover, we retrospectively collected data on patients with PSRCC who received chemo or targeted therapy alone between January 2000 and December 2019. We compared treatment-free interval (TFI), progression-free survival (PFS), treatment-free survival (TFS), overall survival (OS), tumor response, neurologic disturbance of the low extremities, and pelvic pain severity in the different patient groups.ResultsAmong 1295 patients with cervical cancer, we included 28 (2.2%) and 31 (2.4%) in the prospective and retrospective cohorts, respectively. When we subdivided all patients into two groups based on the median value of prior TFI (PTFI, 9.2 months), LEER improved TFI, PFS, TRS and OS compared to chemo or targeted therapy alone (median, 2.8 vs. 0.9; 7.4 vs. 4.1; 30.1 vs. 16.9 months; P ≤ 0.05) in patients with PTFI < 9.2 months despite no difference in survival in those with PTFI ≥ 9.2 months, suggesting that LEER may lead to better TFI, PFS, TRS and OS in patients with PTFI < 9.2 months (adjusted hazard ratios, 0.28, 0.27, 0.44 and 0.37; 95% confidence intervals, 0.12-0.68, 0.11-0.66, 0.18-0.83 and 0.15-0.88). Furthermore, LEER markedly reduced the number of morphine milligram equivalents necessary to reduce pelvic pain when compared with chemo or targeted therapy alone.ConclusionCompared to chemo or targeted therapy alone, LEER improved survival in patients with PSRCC and PTFI < 9.2 months, and it was effective at controlling the pelvic pain associated with PSRCC.Trial RegistrationClinicalTrials.gov, identifier NCT02986568.