Treatment-free Survival Research Articles

Active Surveillance—Is It Feasible for Intermediate-risk Localised Prostate Cancer?

BackgroundAlthough active surveillance (AS) is a well-recognised treatment option for localised low-risk prostate cancer (LRPC), its role in the management of localised intermediate-risk prostate cancer (IRPC) is not clear yet and the available literature is slightly contradictory. ObjectiveTo compare the outcome of AS between LRPC and IRPC patients. Design, setting, and participantsBetween November 2002 and August 2019, 372 men with localised prostate cancer (PC) underwent AS in our hospital based on local departmental protocol. Outcome measurements and statistical analysisThe primary outcome measures were overall survival, disease progression–free survival, treatment-free survival, and biochemical recurrence–free survival. Survival times in the low- and intermediate-risk groups were compared using Cox regression analysis. Results and limitationsOut of 372 localised PC patients, 276 (74%) had LRPC and 96 (26%) IRPC. Overall, 86 (31.2%) low-risk and 25 (26%) intermediate-risk patients developed disease progression, and 86 (31.2%) low-risk and 22 (23%) intermediate-risk patients underwent active treatment. Among the treated patients, eight (2.9%) LRPC patients and one (1%) IRPC patient developed biochemical recurrence. In total, only one patient (from the low-risk group) had metastasis and 25 patients passed away (18 from the low-risk and seven from the intermediate-risk group). No death was recorded due to PC in the cohort. There was no difference in any of the survival outcomes between LRPC and IRPC patients in unadjusted analysis as well as when analysis was performed after adjusting the potentially confounding factors. Limitations include relatively short median follow-up time and failure to objectively define the criteria for the selection of IRPC patients suitable for AS. ConclusionsThe option of AS could be considered for carefully selected and well-informed patients with IRPC provided close structured monitoring is maintained. Patient summaryIn this report, we looked at various survival outcomes of active surveillance between low- and intermediate-risk prostate cancer patients in a large British population. There was no difference in any of the survival outcomes between the two groups. We concluded that carefully selected intermediate-risk prostate cancer patients could be offed the option of active surveillance.

The clinical impact of strict criteria for active surveillance of prostate cancer in Korean population: Results from a prospective cohort.

PurposeTo evaluate the clinical impact of strict selection criteria for active surveillance (AS) of prostate cancer in a Korean population.Materials and MethodsA single-center, prospectively collected AS cohort from December 2016 to February 2019 was used. Following pre-determined criteria, patients were categorized into “strict AS” and “non-strict AS” groups. Clinicopathological progression-free survival (PFS) and treatment-free survival (TFS) of the two groups were compared using the Kaplan–Meier curve and log-rank test. Age-adjusted hazard ratios for clinicopathological progression was calculated using Cox proportional regression analysis.ResultsOf 54 eligible patients, 25 and 29 were assigned to “strict AS” and “non-strict AS,” respectively. Clinicopathological progression and definitive treatment rates were 24.0% (6 of 25 patients) vs. 51.7% (15 of 29 patients) and 32.0% (8 of 25 patients) vs. 62.1% (18 of 29 patients) in “strict AS” and “non-strict AS” groups. Progress to high-risk cancer (pathologic T3 or surgical Gleason Grade 2 over) in radical prostatectomy was higher in “non-strict AS” than “strict AS”. PFS (mean 34.6±2.9 mo vs. 22.6±2.7 mo; p=0.025) and TFS (mean 31.8±3.2 mo vs. 19.6±2.4 mo; p=0.018) favor the “strict AS” group than “non-strict AS” group. Age-adjusted hazard ratio for clinicopathological progression of strict criteria was 0.36 (95% confidence interval, 0.14–0.94; p=0.04).ConclusionsPFS and TFS were better in the “strict AS” group than in the “non-strict AS” group. This finding should be informed to relevant patients during decision making and considered in Korean guidelines.

This Month in Adult Urology

This Month in Adult Urology

A reduced panel of eight genes (ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53) as an estimator of the tumor mutational burden in chronic lymphocytic leukemia.

IntroductionMutational complexity or tumor mutational burden (TMB) influences the course of chronic lymphocytic leukemia (CLL). However, this information is not routinely used because TMB is usually obtained from whole genome or exome, or from large gene panel high‐throughput sequencing.MethodsHere, we used the C‐Harrel concordance index to determine the minimum panel of genes for which mutations predict treatment‐free survival (TFS) as well as large resequencing panels.ResultsAn eight gene estimator was defined encompassing ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53. TMB estimated from either a large panel of genes or the eight gene estimator was increased in treated patients or in those with a short TFS (<2 years), unmutated IGHV gene or with an unfavorable karyotype. Being an independent prognostic parameter, any mutation in the eight gene estimator predicted a shorter TFS better than Binet stage and IGHV mutational status among patients with an apparently non‐progressive disease (TFS >6 months). Strikingly, the eight gene estimator was also highly informative for patients with Binet stage A CLL or with a good prognosis karyotype.ConclusionThese results suggest that the eight gene estimator, that is easily achievable by high‐throughput resequencing, brings robust and valuable information that predicts evolution of untreated patients at diagnosis better than any other parameter.

Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia

AbstractCombination chemotherapy with fludarabine plus cyclophosphamide (FC) was compared with the standard regimen of fludarabine monotherapy in first-line treatment of younger patients with chronic lymphocytic leukemia (CLL). Between 1999 and 2003, a total of 375 patients younger than 66 years who predominantly had advanced CLL were randomly assigned to receive either fludarabine (25 mg/m2 for 5 days intravenously, repeated every 28 days) or FC combination therapy (fludarabine 30 mg/m2 plus cyclophosphamide 250 mg/m2 for 3 days intravenously, repeated every 28 days). Both regimens were administered to a maximum of 6 courses. FC combination chemotherapy resulted in significantly higher complete remission rate (24%) and overall response rate (94%) compared with fludarabine alone (7% and 83%; P < .001 and P = .001). FC treatment also resulted in longer median progression-free survival (48 vs 20 months; P = .001) and longer treatment-free survival (37 vs 25 months; P < .001). Thus far, no difference in median overall survival has been observed. FC caused significantly more thrombocytopenia and leukocytopenia but did not increase the number of severe infections. In summary, first-line treatment with FC increases the response rates and the treatment-free interval in younger patients with advanced CLL.

Salvage Surgery in Patients with Local Recurrence After Radical Prostatectomy

BackgroundSince the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, isolated local recurrence after radical prostatectomy (RP) can be delineated accurately. ObjectiveTo describe and evaluate surgical technique, biochemical response, and therapy-free survival (TFS) after salvage surgery in patients with local recurrence in the seminal vesicle bed. Design, setting, and participantsWe retrospectively assessed 40 patients treated with open salvage surgery in two centres (11/2014-02/2020). All patients presented with biochemical recurrence (BCR) after RP with a singular local recurrence at PSMA PET imaging. Thirty-three (82.5%) patients received previous salvage radiation therapy. Surgical procedureOpen salvage surgery with PSMA radioguidance. MeasurementsProstate-specific antigen (PSA) nadir and percentage of patients with complete biochemical response (cBR) without further treatment (PSA < 0.2 ng/ml) after 6–16 wk were assessed. BCR-free survival and TFS were calculated using Kaplan-Meier estimates. Clavien-Dindo complications were evaluated. Results and limitationsPrior to salvage surgery, median PSA was 0.9 ng/ml (interquartile range [IQR]: 0.5–1.7 ng/ml). Postoperatively, median PSA nadir was 0.1 ng/ml (IQR: 0–0.4 ng/ml). In 31 (77.5%) patients, cBR was observed. During the median follow-up of 24.4 months, 22 (55.0%) patients experienced BCR and 12 (30.0%) received further therapy. At 1 yr of follow-up, BCR-free survival rate was 62.2% and TFS rate was 88.3%. Three (7.5%) Clavien-Dindo grade III complications were observed. The main limitations are the retrospective design, short follow-up, and lack of a control group. ConclusionsSalvage surgery of local recurrence within the seminal vesicle bed is feasible. It may present an opportunity in selected, locally recurrent patients to prolong BCR-free survival and increase TFS. Further studies are needed to confirm our findings. Patient summaryWe looked at the outcomes from prostate cancer patients with locally recurrent disease after radical prostatectomy and radiotherapy. We found that surgery in well-selected patients may be an opportunity to prolong treatment-free survival.

PCN333 Analysis of Hospital Episode Statistics Data to Demonstrate the Secondary Care Treatment Pathway and Outcomes of Patients with Cutaneous T-Cell Lymphoma in England

This study aimed to describe the real-world demographics, management, clinical outcomes and healthcare resource use (HCRU) and costs of UK patients with Mycosis Fungoides (MF) and Sézary Syndrome (SS). Patients with ICD-10 diagnoses of MF (C84.0) or SS (C84.1) in the National Health Service’s Hospital Episode Statistics (HES) database between 1-Oct-2010 and 31-Mar-2019 were included, with secondary care activity tracked from diagnosis to study end date/death. Overall survival (OS) was calculated from date of diagnosis until death (or censored at study end date, if still alive). Next treatment-free survival (NTFS) was calculated from diagnosis until the date a new systemic (non-topical) treatment (of those available in HES) was started or added to existing treatment, or death. OS and NTFS were also calculated from the start of the next new systemic treatment. HCRU costs were estimated per patient/week. 1,737 patients with MF and 165 patients with SS (MF: mean age at diagnosis=65 years, 62% male; SS: mean age=66 years, 48% male) were included. 513 (30%) patients with MF and 58 (35%) with SS had ≥1 change in treatment and 554 (32%) MF and 88 (53%) SS patients died during the study period. Median OS for SS was 2.6 years (median not reached for MF) and median NTFS was 4.6 years (MF) and 1.0 years (SS). From start of the next new treatment, median OS was 1.5 years (MF) and 1.0 years (SS) and median NTFS was 0.3 years (MF) and 0.3 years (SS). Mean total HCRU costs varied between £53.07-£105.70 (MF) and £ 29.36-£135.93 (SS) per patient/week depending on the treatment line. HES data highlighted the significant real-world burden of MF and SS in England, demonstrating that many patients managed within the secondary care setting experience multiple treatment changes and poor survival outcomes, with high HCRU costs.

Circulating Tumour DNA in Advanced Melanoma Patients Ceasing PD1 Inhibition in the Absence of Disease Progression.

Simple SummaryImmunotherapy is an effective treatment that harnesses the immune system to fight cancer. Drugs such as immune checkpoint inhibitors have demonstrated efficacy in the treatment of advanced melanoma. However, the optimal duration of treatment is not well established. The aim of our retrospective study was to analyse the outcomes of patients who have stopped immunotherapy treatment for advanced melanoma after durable disease control. Furthermore, we assessed circulating tumour DNA (ctDNA), which is shed from the tumour into the bloodstream, to determine its validity as a predictive biomarker of disease progression after treatment was stopped. We demonstrated that stopping treatment after durable disease control results in excellent short- to medium-term prognosis and ctDNA present at the time of stopping treatment is a strong predictor of disease recurrence.Immunotherapy is an important and established treatment option for patients with advanced melanoma. Initial anti-PD1 trials arbitrarily defined a two-year treatment duration, but a shorter treatment duration may be appropriate. In this study, we retrospectively assessed 70 patients who stopped anti-PD1 therapy in the absence of progressive disease (PD) to determine clinical outcomes. In our cohort, the median time on treatment was 11.8 months. Complete response was attained at time of anti-PD1 discontinuation in 61 (87%). After a median follow up of 34.2 months (range: 2–70.8) post discontinuation, 81% remained disease free. Using ddPCR, we determine the utility of circulating tumour DNA (ctDNA) to predict progressive disease after cessation (n = 38). There was a significant association between presence of ctDNA at cessation and disease progression (p = 0.012, Fisher’s exact test) and this conferred a negative and positive predictive value of 0.82 (95% CI: 0.645–0.930) and 0.80 (95% CI 0.284–0.995), respectively. Additionally, dichotomised treatment-free survival in patients with or without ctDNA at cessation was significantly longer in the latter group (p < 0.001, HR: 0.008, 95% CI: 0.001–0.079). Overall, our study confirms that durable disease control can be achieved with cessation of therapy in the absence of disease progression and undetectable ctDNA at cessation was associated with longer treatment-free survival.

A single-center long-term experience of active surveillance for prostate cancer: 15 years of follow-up.

PurposeTo describe a single-center 15-year experience of active surveillance (AS) for prostate cancer (PCa).Materials and MethodsWe retrospectively reviewed patients who underwent AS between 2003 and 2018. One hundred fifty-three patients were selected according to the following criteria: (1) biopsy Gleason pattern ≤3+4 with (2) ≤two positive core(s) and (3) ≤50% core involvement, clinical-stage ≤T2a, and prostate-specific antigen (PSA) ≤20 ng/mL. Follow-up included PSA measurement every six months, prostate biopsies at one year and then every 2–3 years, and MRI every year. Intervention was triggered by (1) Gleason score (GS) upgrading, (2) >two positive cores, or (3) PSA doubling-time in <3 years.ResultsMean (±standard deviation) follow-up was 36.4 (±31.9) months. Ninety-three (60.8%) and 20 (13.1%) patients received second and third biopsies, respectively. Seventy-two patients (47.1%) discontinued AS for various reasons (59, intervention; 13, follow-up loss). Reasons for intervention consisted of GS upgrading (42.4%), >two positive cores (8.5%), abnormal PSA kinetics (11.9%), and patient preference (37.3%). Notably, 12 (25.5%) patients had pathologic GS ≥4+3 (unfavorable disease) and 3 (6.4%) patients had pathologic stage ≥T3a at radical prostatectomy. Median time to treatment-free survival was 19.5 months. Of the 59 patients who switched to intervention, biochemical recurrence was reported in only one (0.7%) patient.ConclusionsAS is an available option for low-risk PCa in carefully selected patients. Further larger prospective studies are needed to determine the optimal criteria for AS, especially in Korean PCa patients.

SURG-31. SURGICAL OUTCOME ANALYSES ON 244 CENTRAL NERVOUS SYSTEM HEMANGIOBLASTOMA

Abstract BACKGROUND Surgical resection of the central nervous system hemangioblastoma is often challenging, with vascular-rich nature and surrounding critical structures. von Hippel-Lindau (VHL) disease cases make the management more difficult with repeated surgeries required for multiple lesions. Here we investigated the surgical outcome of CNS HGBs on a large cohort to clarify the clinical and radiological parameters pertaining to the surgical success. METHODS Retrospective analysis of consecutive, neurosurgically managed CNS HGB at Mayo Clinic, 1988-2018. RESULTS Total 244 surgeries were performed for 172 patients. Gross total resection (GTR) was achieved in 90.0%, which was lower in cases brainstem lesions (78.3%) and was associated with the tumor, especially solid-portion volume (p=0.017). Intraoperative blood loss correlated with the size of solid portions, and the transfusion was performed in 7.5%. Postoperative complication was observed in 52.2%, including new/worsening neurological deficit in 45.4%, wound complication in 9.1% and systemic complication in 4.0%. Postoperative rehabilitation was introduced in 61.7% of the patients, which was statistically associated with age, non-GTR and tumor location (brainstem and spine) on multivariate analysis (p=0.0031, 0.027 and 0.0066, respectively). Treatment-free survival was longer in VHL (vs sporadic) cases and GTR (vs non-GTR) cases, and multivariate analysis showed GTR was the only factor associated with treatment-free survival (p=0.0015). CONCLUSIONS Surgery for CNS HGBs was shown to be challenging, with abundant intraoperative bleeding and high risk of postoperative complications necessitating rehabilitation. GTR of the lesion is of utmost importance, which increases the chance of long treatment-free survival as well as favorable direct postoperative clinical course.

ENESTop 5-Year Update: Durability of Treatment-Free Remission Following Second-Line Nilotinib and Exploratory Analysis of Molecular Response Regain after Nilotinib Re-Initiation in Patients with Chronic Myeloid Leukemia

ENESTop 5-Year Update: Durability of Treatment-Free Remission Following Second-Line Nilotinib and Exploratory Analysis of Molecular Response Regain after Nilotinib Re-Initiation in Patients with Chronic Myeloid Leukemia

Efficacy and Safety of Front-Line Nilotinib Treatment and Discontinuation in Older Patients (≥65 years) with Chronic Myeloid Leukemia in Chronic Phase Who Have Achieved MR4.5: Results from ENESTfreedom

Efficacy and Safety of Front-Line Nilotinib Treatment and Discontinuation in Older Patients (≥65 years) with Chronic Myeloid Leukemia in Chronic Phase Who Have Achieved MR4.5: Results from ENESTfreedom

CTP Synthase 2: A Novel Prognostic Biomarker and Potential Therapeutic Target in Chronic Lymphocytic Leukemia

Introduction CTP synthase 2 (CTPS2) is a critical regulator in lymphocytes proliferation and nucleotides synthesis. Yet, the role of CTPS2 has not been explored in chronic lymphocytic leukemia (CLL). Hence, the aim of this study was to investigate the clinical significance and functional mechanism of CTPS2 regulation in CLL pathogenesis and progression. Methods In the present study, 1030 clinically annotated CLL patients from multiple cohorts were enrolled with informed consents. Peripheral blood samples from 66 de novo CLL patients were collected at the Department of Hematology in Shandong Provincial Hospital. Expression levels of CTPS2 in CLL cells were determined by quantitative RT-PCR and western blotting. Lentiviral vectors were utilized to stably silence CTPS2. RNA-sequencing and functional enrichment analysis were performed. Besides, cell viability, apoptosis and cell cycle were assessed by cell counting kit-8, annexin V-PE/7AAD and PI/RNase staining, respectively. All investigators comply with the guiding principles for experimental procedures found in the Declaration of Helsinki of the World Medical Association. Results Aberrantly increased expression of CTPS2 was detected in CLL primary cells and cell lines (MEC1 and EHEB) at mRNA and protein level compared with normal B cells (p&amp;lt;0.001; Figure 1A). To validate the altered pattern of CTPS2 expression in CLL, we further investigated and found CTPS2 over-expression in CLL patients in 3 independent microarrays (p&amp;lt;0.01; Figure 1B-C). In addition, we observed elevated CTPS2 expression in significant correlation with advanced Binet stage (p&amp;lt;0.001; Figure 1D), unmutated IGHV (p=0.007; Figure 1E), and deletion of 11q23 (p&amp;lt;0.001; Figure 1F). Kaplan-Meier curves showed stratified CTPS2high patients were observed with significantly shorter overall survival versus the CTPS2low group in 2 independent cohorts (cohort 1, HR=4.488, p=0.001, Figure 2A; cohort 2, HR=1.614, p=0.049, Figure 2B). Besides, enhanced expression of CTPS2 were revealed to predict inferior treatment-free survival (cohort 1, HR=2.715, p=0.003, Figure 2C; cohort 2, HR=1.909, p=0.008, Figure 2D). Univariate cox regression analysis suggested that CTPS2 high expression predicted adverse survival (HR=1.785, p=0.003). Moreover, multivariate cox regression analysis confirmed the prognostic value of CTPS2 overexpression in CLL patients independent of age and Binet stage (HR=1.724, p=0.007; Figure 2E). To investigate the biological processes of CTPS2 involving in CLL progression, functional assays were performed. CLL cells with CTPS2 silencing exhibited attenuated cell proliferation, increased fast-onset apoptosis and induced G2/M phase arrest (Figure 3A-E). Additionally, down-regulated Bcl-2 expression as well as promoted cleaved-PARP, Bax and p21 expression were observed in CTPS2 knock-down transfected CLL cells (Figure 3F). To further explore the mechanism of CTPS2 regulation in the tumorigenesis of CLL, RNA-sequencing was conducted in CLL transfected cells. Annotations of differentiated genes implicated that CTPS2 was functionally enriched in cell cycle, DNA replication activation and oncogenic pathways (Figure 4A). Accordantly, activation of p-ATM, p-BRAC1, p-H2AX were visibly elevated, illuminating the potential mechanism of CTPS2 regulating DNA damage in CLL pathogenesis (Figure 4B). Collectively, the interactive network of CTPS2 and its down-stream targets was established, illuminating the potential mechanism of CTPS2 regulation in CLL progression (Figure 4C). Conclusion Taken together, the present study was the first investigation on the role of CTPS2 in CLL tumorigenesis by in silico analysis and ex vivo evaluation. CTPS2 was up-regulated and conferred independent inferior prognostic significance, highlighting the effectiveness and potential of CTPS2 in risk stratification and targeted strategy in CLL patients. Disclosures No relevant conflicts of interest to declare.

Association Between Black Race And Improved Survival Following Sipuleucel-T Immunotherapy In Metastatic Castrate-Resistant Prostate Cancer: Implications For Immune Biology And Integration Of Radiation Therapy With Immunotherapy

The biology of prostate cancer in black patients may differ from white patients. For example, recent data suggests that black patients may harbor tumors that are more sensitive to radiation or immune-directed therapy. Sipuleucel-T, a cell-based immunotherapy approved for use in men with metastatic castrate-resistant prostate cancer (mCRPC), is currently also being studied in early-stage non-metastatic prostate cancer. To explore possible immunologic differences and opportunities for synergy with radiation therapy, we examined the association between race and overall survival (OS) among patients receiving sipuleucel-T therapy for mCRPC using a novel real-world database. Using the CancerLinQ database, we identified 474 patients with mCRPC managed with sipuleucel-T. We used Cox modeling to examine the association between race (black vs white) and OS, with or without adjustment for other prognostic variables (age, prior systemic therapy, and prostate-specific antigen [PSA]), and performed subgroup analyses stratifying by the median PSA (16.6 ng/mL). In secondary analyses, we used Cox modeling to estimate treatment-free survival following sipuleucel-T and we used competing risks regression to model time to initiation of a subsequent systemic therapy. Median follow-up was 38.8 months. Black patients (n = 68) experienced significantly improved OS compared to white patients (n = 406) (median 43.1 months vs 30.2 months, hazard ratio [HR] = 0.638, 95% confidence interval [CI] 0.443-0.920, p = 0.016). These results persisted on multivariable analysis (adjusted HR 0.542, 95% CI 0.371-0.792, p = 0.002). Among patients with PSA > 16.6 ng/mL, median OS was 37.7 months vs 20.3 months (HR = 0.463, 95% CI 0.277-0.775, p = 0.003). For patients with PSA < = 16.6 ng/mL, there was no significant difference in median OS (43.1 months vs 40.6 months, HR = 0.842, 95% CI 0.487-1.456, p = 0.538). There were no significant differences in treatment-free survival (HR = 0.777, 95% CI 0.581-1.040, p = 0.090) or initiation of a subsequent systemic therapy (HR = 1.287, 95% CI 0.802-2.065, p = 0.295) by race. Black patients were more likely to receive subsequent cabazitaxel therapy compared to white patients (26.5% vs 15.0%, p = 0.019) but there were no significant differences in the receipt of other therapies (docetaxel, abiraterone, enzalutamide, radium-223). Among men with mCRPC who received sipuleucel-T, black patients had significantly longer OS compared to white patients but no difference in the time to subsequent systemic therapy, mirroring the results of prior immunotherapy studies. This finding may reflect differences in the underlying immune biology of prostate cancer in black versus white patients and may have implications for the integration of radiation therapy and immunotherapy in prostate cancer.

Combined Expression of CD34 and FLT3-Internal Tandem Duplication Mutation Predicts Poor Response to Treatment in Acute Myeloid Leukemia.

BackgroundAcute myeloid leukemia (AML) is a common hematological malignancy associated with different cytogenetic and genetic abnormalities.MethodsFLT3-internal tandem duplication (FLT3/ITD) mutation and CD34 expression levels were assessed in the bone marrow (BM) aspirates of 153 de novo AML patients. Data were correlated with relevant clinic-pathological features of the patients, response to treatment, disease-free survival (DFS), and overall free survival (OS) rates.ResultsFLT3-ITD mutation was detected in 27/153 (17.6%) AML patients (P=0.001), and CD34 was expressed in 83/153 (54.2%) patients (P=0.293) compared to those with wild FLT3 and CD34− expression, respectively. Patients with FLT3-ITD mutation showed increased peripheral blood and BM blast cells, abnormal cytogenetics, poor DFS and OS compared to those with wild FLT3 (P=0.013, P<0.001, P=0.010, P=0.008 and P=0.004, respectively), while there was no significant association with response to treatment (P=0.081). There was no significant association between CD34 expression and response to treatment, DFS, and OS (P>0.05). FLT3-ITD mutation and FAB subtypes were independent prognostic factors for DFS. Older age ≥39 years, HB <7 mg/dL PB blast ≥54%, and FLT3-ITD mutation were independent prognostic factors for poor OS in AML patients. The presence of both FLT3-ITD mutation and CD34 expression associated significantly with resistance to therapy (P=0.024), short DFS and OS rates (P=0.006, P=0.037, respectively).ConclusionCombined expression of both FLT3-ITD mutation and CD34 expression is an important prognostic and predictive factor for poor disease outcome in AML patients.

Impact of Early Confirmatory Tests on Upgrading and Conversion to Treatment in Prostate Cancer Patients on Active Surveillance

To assess the impact of confirmatory tests on active surveillance (AS) biopsy disease reclassification and progression to treatment in men with favorable risk prostate cancer (FRPC). We searched the MUSIC registry for men with FRPC managed with AS without or with a confirmatory test. Confirmatory tests included (1) repeat prostate biopsy, (2) genomic tests, (3) prostate magnetic resonance imaging (MRI), or (4) MRI followed by a post-MRI biopsy. Confirmatory test results were deemed reassuring (RA) or nonreassuring (nonRA) according to predefined criteria. Kaplan-Meier curves and multivariable Cox regression models were used to compare surveillance biopsy disease reclassification-free survival and treatment-free survival. Of the 2,514 men with FRPC who were managed on AS, 1211 (48%) men obtained a confirmatory test. We noted differences in the 12-month unadjusted surveillance biopsy disease reclassification-free probability (68%, 83%, and 90%, P < .0001) and 24-month unadjusted treatment-free probability (55%, 81%, and 79%, P < .0001), for men with nonRA confirmatory tests, no confirmatory test, and RA confirmatory tests, respectively. Excluding patients with genomic confirmatory tests, men with RA confirmatory tests were associated with a lower hazard (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.38-0.84, P = .005) and men with nonRA confirmatory tests had an increased hazard (HR 1.97, 95% CI 1.22-3.19, P = .006) of surveillance disease reclassification compared with men without confirmatory tests in the multivariable model. These data suggest men with RA confirmatory tests have less surveillance biopsy reclassification and remain on AS longer than men with nonRA test results. Confirmatory tests may help risk stratify men considering active surveillance.

Technical Refinements in Superextended Robot-assisted Radical Prostatectomy for Locally Advanced Prostate Cancer Patients at Multiparametric Magnetic Resonance Imaging

BackgroundThe feasibility and efficacy of robot-assisted radical prostatectomy (RARP) in locally advanced prostate cancer (PCa) patients with iT3 lesion at magnetic resonance imaging (MRI) are currently not explored. ObjectiveTo describe our revised RARP technique (ie, superextended RARP [SE-RARP]) for PCa patients with posterior iT3a or iT3b at MRI. Design, setting, and participantsData from 89 patients with posterior iT3a or T3b disease who underwent SE-RARP at a single high-volume centre between 2015 and 2018 were analysed. Surgical procedureRARP was performed using a DaVinci Xi system. The surgical approach provided an inter- or extrafascial RARP where Denonvilliers’ fascia and perirectal fat were dissected free and left on the posterior surface of the seminal vesicles. MeasurementsPerioperative outcomes, and intra- and postoperative complications were assessed. Postoperative outcomes were assessed in patients with complete follow-up data (n = 78). Biochemical recurrence (BCR) was defined as two consecutive prostate-specific antigen values of ≥0.2 ng/ml. Urinary continence (UC) recovery was defined as the use of zero or one safety pad. Kaplan-Meier and multivariable Cox regression models were used. Results and limitationsThe median operative time, blood loss, and length of stay were 204 min, 300 ml, and 5 d, respectively. The median bladder catheterisation time was 5 d. Overall, 28%, 28%, and 27% of patients had pathological grade group (GG) 4–5, pT3b, and positive surgical margins (PSMs), respectively. Three patients (3.4%) experienced intraoperative complications. Among patients with available follow-up data (n = 78), 14 (18%) experienced 30-d postoperative complications. The median follow-up was 19 mo. Overall, 11 patients received additional treatment. At 2 yr of follow-up, BCR-free and additional treatment–free survival were 55% and 66%, respectively. Pathological GG 4–5 (hazard ratio [HR] 3.2) and PSM (HR 5.8) were independent predictors of recurrence, as well as of additional treatment use (HR 5.6 for GG 4–5 and 5.2 for PSM). The 1-yr UC recovery was 84%. ConclusionsWe presented our revised RARP technique applicable to patients with posterior iT3a or iT3b at preoperative MRI. This technique is associated with good morbidity and continence recovery rates, and might guarantee biochemical control of the disease and postpone the use of additional treatments in patients with low-grade and negative surgical margins. Patient summaryA revised robot-assisted radical prostatectomy technique applicable to prostate cancer patients with posterior iT3a or iT3b lesion at magnetic resonance imaging was described. This novel technique is feasible and safe in expert hands.

Surveillance active du cancer de prostate : survie sans traitement curatif selon critères d’éligibilité stricts ou élargis

Overtreatment is an actual problem in low risk localized prostate cancer (PC) management. Active surveillance (AS) is a solution to limit this problem, but eligibility criteria remained discussed. The aim was to assess possibilities of widening selection criteria for patient in AS, studying curative treatment free survival (CTFS) according to restricted or expanded eligibility criteria. We retrospectively studied patients beginning AS between 2008 and 2014, for Gleason 6 localized PC, PSA<15ng/ml,<cT3. The group "strict criteria" was defined:≤cT2a, PSA<10ng/ml, 2≤positive biopsies (PB+), total tumoral length≤3mm, tumoral invading≤50%, PSA density≤0,15ng/ml/cm3. MRI was performed at baseline and during follow-up. Radical treatment was proposed in case of biological, histological or clinical progression. Criteria associated with AS survival were analyzed by Cox regression. One hundred eighty patients were included (follow-up 46 months). One hundred and eleven patients had "strict" criteria vs. 69 "expanded" criteria. Eighty-two patients (45%) were treated with median time of 18.2 months (CTFS was 71% at 2 years, 52% at 5 years.). The widening of the inclusion criteria was not associated with CTFS (65 vs 54% at 5 years, P=0.13). Factors significatively associated with discontinuation of AS were bilaterality (HR=2.12) and abnormal rectal digital examination cT2 (HR=2,07); MRI target (HR=2,48)) tended towards significance. Our study concludes that curative treatment free survival is similar for patients included with expanded criteria compared with those included with strict criteria. However, high initial cancer volume) is associated with AS discontinuation. 3.

Résultats de la surveillance active des angiomyolipomes sporadiques du rein de plus de 4 cm : un plaidoyer en faveur de la surveillance active

Active surveillance (AS) of sporadic renal angiomyolipomas (AML) is under-utilised because of an old dogma fearing a life-threatening retroperitoneal hemorrhage when tumour size exceeds 4cm. The objective of this study was to report the outcome of AS in patients with sporadic AML greater than 4cm. The results of AS in 35 patients managed for sporadic renal AML greater than 4cm were analysed. During AS, tumour growth, occurrence of new symptoms and/or complications, discontinuation of AS protocol, reason for discontinuation as well as subsequent treatment options were reported. Within a median follow-up of 36months, 16 (46%) patients discontinued AS at the end of the study period (mean follow-up 55±66, median 36months). Patients who discontinued AS were more symptomatic at diagnosis but had similar age, mean tumour size and sex ratio. Active treatment-free survival was 66% at 5years. Retroperitoneal hemorrhage was reported in 3 (8.5%) patients. None of these bleedings required transfusion or monitoring in an intensive care unit. Other reasons for discontinuation were pain (37%), patient preference (19), changes in the radiological appearance of the tumour (19%), and hematuria (6%). This study showed that AS in AML bearing patients was feasible even in the setting of tumours larger than 4cm. More than 50% of the patients were still on AS at 5 years. Discontinuation of AS was not related to bleeding complications in most cases. 3.

713P Treatment-free survival, with and without toxicity, after immuno-oncology vs targeted therapy for advanced renal cell carcinoma (aRCC): 42-month results of CheckMate 214

713P Treatment-free survival, with and without toxicity, after immuno-oncology vs targeted therapy for advanced renal cell carcinoma (aRCC): 42-month results of CheckMate 214