History Of Prior Pelvic Radiation Research Articles

Abstract 1123: Genomic characterization of radiotherapy-associated bladder cancer

Abstract Background: Bladder cancer (BCa) is the 4th most common cancer diagnosed in men, with 82,290 new cases predicted in 2023. As BCa frequently occurs at an advanced patient age, its diagnosis may follow radiotherapy (RT) for the treatment of prostate cancer. Currently, data is limited regarding the influence of RT on the clinical course and genomic landscape of subsequent BCa, mainly due to a paucity of samples. From prior studies, pelvic radiation confers an increased risk of BCa, with resulting tumors that are largely genomically similar to non-RT tumors with the exception of an increase rate of genomic insertions. Our current study looks to expand on these findings by characterizing the genomes of the largest cohort of RT-associated bladder cancers to date. Methods: We identified BCa cases from patients with a prior history of pelvic radiation for prostate cancer, and tumor only targeted sequencing was performed using Foundation Medicine (FMI) on FFPE tissue (n=41). For control cases (CTRL), patients with no prior record of pelvic radiation and who had previously underwent standard of care FMI sequencing were included (n=41). Sequencing data were re-aligned to hg38 and mutation calling was performed on the newly aligned sequences. Results: CTRL and RT cohorts had similar distributions of patients based on race and smoking status. While cT stage was similar between the two cohorts, the CTRL cohort was biased toward higher cN and cM stages with no difference in overall survival (median OS: CTRL = 20m, RT = 23m), though the advanced stage of the CTRL cohort could mask a worse prognosis in the RT cohort. Latency specific analysis revealed short latency tumors (<10 years from RT) had a significantly shorter overall survival than long latency tumors (p<0.01, HR=5.59, CI=1.81-17.3), and a numerically, but not significantly, shorter survival than CTRL patients (p=0.17, HR=1.55, CI=0.82-2.94). Long latency tumor patients had a significantly longer overall survival than CTRL patients (p<0.01, HR = 0.22, CI=0.07-0.63). In line with prior studies, RT samples had increased numbers of insertions (p<0.01). In addition, we also detected an increase in SNVs in the RT samples (p<0.01). Of note, KDM6A alterations were enriched within the RT cohort (CTRL = 10/41, RT = 30/41, p<0.001), with series of splice site mutations exclusive to RT samples (p<0.001). Conclusion: Patients diagnosed with BCa within a short interval following pelvic radiation have a worse prognosis. Genomic analysis showed RT-associated tumors having an increased number of insertions, SNVs, and KDM6A splice site mutations compared to non-RT tumors. Overall, the spectrum of recurrent alterations within the cohorts were consistent with previous studies, with the exception of the KDM6A mutations. To our knowledge, this is the first report of a RT-associated alteration in a specific gene in bladder cancer and additional studies will be needed to validate and understand the consequences of this finding. Citation Format: N. Ari Wijetunga, Kathryn H. Gessner, Krishna Kanchi, Sara E. Wobker, David Corcoran, Matthew D. Galsky, Matthew I. Milowsky, William Y. Kim, Tracy L. Rose, Jeffrey S. Damrauer. Genomic characterization of radiotherapy-associated bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1123.

Cesium-131 Low-Dose Rate Interstitial Brachytherapy as a Salvage Re-Irradiation Technique in Treating Cervical and Uterine Cancer Pelvic Recurrence with Prior History of Pelvic Radiation

Pelvic recurrence among cervical and uterine cancer patients with prior history of pelvic radiation is a poor prognostic factor and remains challenging. The standard of care is pelvic exenteration, which is a highly morbid surgical procedure. The purpose of this study is to report local control rate and toxicity profile of Cesium-131 low-dose rate interstitial brachytherapy (LDR) as a salvage re-irradiation technique in managing pelvic relapse. We reviewed procedures and outcomes from patients with previously irradiated uterine corpus or cervix neoplasms, who subsequently relapsed and then underwent cesium-131 LDR implants between January 2016 and December 2022. Patient demographics, treatment planning variables, and disease response were reviewed. Acute toxicities, late toxicities, and local control rate were compiled for this study. A total of 12 eligible patients (6 cervical and 6 uterine cancer) with 16 cesium-131 LDR implants were included in this study. The majority (75%) of pelvic relapses occurred at the exocervix (cervix-intact) or vaginal cuff (post-hysterectomy). Median time from disease relapse to cesium implant was 32 days. The average area of implementation was 9 cm2 and average number of seeds implanted was 16. The mean prescription dose was 50 Gy. Six patients also received high-dose rate vaginal intracavitary brachytherapy in addition to cesium-131 LDR. Median follow up was 12 months. 81% of cesium implants achieved complete response at first post-treatment follow-up, while the remaining 19% demonstrated partial response. The 6-months local control rate was 79%. After cesium implant, 25% patients had local recurrence and 33% with distal metastasis. The most reported acute toxicities included vaginal mucositis (63%), dysuria (50%) and pain (19%). All patients had various degrees of vaginal stenosis and strictures long-term. Only 1 (8%) out of 12 patients, with 4 repeated cesium-131 LDR implants, developed a rectovaginal fistula and chronic pain. Cesium-131 LDR interstitial brachytherapy is a safe and feasible salvage re-irradiation technique in treating pelvic relapse among uterine corpus or cervix cancer patients with prior history of pelvic radiation. Local control rate at 6-months was acceptable with minimum toxicity. Long-term follow up is warranted to validate the efficacy of cesium-131 LDR. We conclude that cesium-131 LDR interstitial brachytherapy is a promising alternative to pelvic exenteration in selective patient population. Future prospective study is warranted.

MP56-13 PERIOPERATIVE AND SURVIVAL OUTCOMES OF PATIENTS WITH A HISTORY OF PELVIC RADIATION UNDERGOING SALVAGE ROBOT-ASSISTED RADICAL CYSTECTOMY. AN RRC-ICUD COLLABORATIVE STUDY

You have accessJournal of UrologyCME1 Apr 2023MP56-13 PERIOPERATIVE AND SURVIVAL OUTCOMES OF PATIENTS WITH A HISTORY OF PELVIC RADIATION UNDERGOING SALVAGE ROBOT-ASSISTED RADICAL CYSTECTOMY. AN RRC-ICUD COLLABORATIVE STUDY Giovanni Cacciamani, Joge Ballon, Viktor Skokic, Gus Miranda, John Sfakianos, Etienne Lavallee, Yuan Shuo Wang, Linda Dey, Arad Hosseini, Juhana Rautiola, Gunnar Steineck, Monish Aron, Inderbir Gill, Abolfazl Hosseini, Reza Mehrazin, Peter Wiklund, and Mihir Desai Giovanni CacciamaniGiovanni Cacciamani More articles by this author , Joge BallonJoge Ballon More articles by this author , Viktor SkokicViktor Skokic More articles by this author , Gus MirandaGus Miranda More articles by this author , John SfakianosJohn Sfakianos More articles by this author , Etienne LavalleeEtienne Lavallee More articles by this author , Yuan Shuo WangYuan Shuo Wang More articles by this author , Linda DeyLinda Dey More articles by this author , Arad HosseiniArad Hosseini More articles by this author , Juhana RautiolaJuhana Rautiola More articles by this author , Gunnar SteineckGunnar Steineck More articles by this author , Monish AronMonish Aron More articles by this author , Inderbir GillInderbir Gill More articles by this author , Abolfazl HosseiniAbolfazl Hosseini More articles by this author , Reza MehrazinReza Mehrazin More articles by this author , Peter WiklundPeter Wiklund More articles by this author , and Mihir DesaiMihir Desai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003309.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There are lack of data on salvage robot-assisted radical cystectomy (sRRC) after pelvic radiation therapy (RT) in patients with bladder cancer. We present perioperative, oncological, and long terms survival outcomes for patients with a history of pelvic radiation who had undergone sRRC from 3 high-volume centers. METHODS: Data from prospectively maintained databases from 3 centers (USC, Karolinska Institute, Mount Sinai) from 2009-2019 were retrospectively reviewed. Patients with a history of pelvic radiation who underwent sRRC with Intracorporeal (ICUD) or extracorporeal (ECUD) for intent to cure bladder cancer were identified. Using a propensity score estimation (based on age, BMI, gender, ASA score, neoadjuvant chemotherapy, and clinical tumor stage (Caliper size 0.2), patients were matched 1:1 to a cohort undergoing RRC without prior history of pelvic radiation. Both groups were compared for perioperative, oncologic, and survival outcomes with up to 3 years of follow-up. RESULTS: A total of 92 sRRC were PS matched to 92 patients undergoing RRC. While both groups were similar in the proportion of ICUD (70.3 vs 78.3%, p=0.29), the sRRC had a lower proportion of continent diversion (6.7 vs 22.8%, p=0.004)). There were no significant differences between the 2 groups in operative time (333.8 vs 348.2 minutes, p=0.246), postoperative complications, at 30 days (p=0.36), and 31-90 days (p=0.64), and readmission rates at 30 days (16.3 vs 19.6%, p=0.70) and 31-90 days (16.5 vs 21.8%, p=0.48). The sRRC group had a lower number of lymph nodes (LNDs) retrieved (20.1 vs 29, p≤0.001), positive LNDs (0.3 vs 1.7, p=0.007), and positive LNDs rate (0.03 vs 0.07%, p=0.035). However no significant differences observed in tumor stage (p=0.41) and LNDs stage (p=0.065) and rate (23.9 vs 29.3; p=0.5). At 3 years, OSS (59.1 vs 67.8% p=0.27), CSS (74.9 vs 74.4% p=0.59), and RFS (70.7 vs 76.1 p=0.67) were similar between sRRC and RRC. CONCLUSIONS: This largest multi-institutional contemporary study provides the best evidence to date supporting the feasibility of sRRC. Perioperative and survival outcomes were comparable between the two groups indicating that sRRC is feasible for selected patients who have underwent pelvic RT. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e779 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giovanni Cacciamani More articles by this author Joge Ballon More articles by this author Viktor Skokic More articles by this author Gus Miranda More articles by this author John Sfakianos More articles by this author Etienne Lavallee More articles by this author Yuan Shuo Wang More articles by this author Linda Dey More articles by this author Arad Hosseini More articles by this author Juhana Rautiola More articles by this author Gunnar Steineck More articles by this author Monish Aron More articles by this author Inderbir Gill More articles by this author Abolfazl Hosseini More articles by this author Reza Mehrazin More articles by this author Peter Wiklund More articles by this author Mihir Desai More articles by this author Expand All Advertisement PDF downloadLoading ...

MP42-01 CLINICAL FACTORS ASSOCIATED WITH 90-DAY MORBIDITY FOLLOWING SURGICAL MANAGEMENT OF UROSYMPHYSEAL FISTULA

You have accessJournal of UrologyCME1 Apr 2023MP42-01 CLINICAL FACTORS ASSOCIATED WITH 90-DAY MORBIDITY FOLLOWING SURGICAL MANAGEMENT OF UROSYMPHYSEAL FISTULA Elizabeth Bearrick, Jayson Kemble, Samuel Broida, Matthew Houdek, and Boyd Viers Elizabeth BearrickElizabeth Bearrick More articles by this author , Jayson KembleJayson Kemble More articles by this author , Samuel BroidaSamuel Broida More articles by this author , Matthew HoudekMatthew Houdek More articles by this author , and Boyd ViersBoyd Viers More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003280.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urosymphyseal fistula (USF) is a devastating complication associated with prostate cancer therapy treatment. Definitive surgical management including fistula decompression, removal of devitalized bone, and tissue interposition remain the gold standard. Early postoperative outcomes remain underreported. The aim of this study was to characterize 90-day morbidity and clinical characteristics associated with adverse outcomes. METHODS: A retrospective chart review of a single institutional database identified 54 patients who underwent operative treatment for USF. Clinical characteristics and 90-day morbidity were assessed. RESULTS: In total, 46/54 (85%) patients had a history of prior pelvic radiation. Cystectomy with urinary conduit was common (N=39, 72%) and 7 (13%) underwent a robotic approach. Discordance between intra and preoperative cultures was present in 34 (67%) including 10/21 (48%) with fungal growth. Median length of stay was 9 days (IQR 7-15), 90-day Clavien-Dindo grade ≥3 complications occurred in 19 (35%), including reoperation in 7 (13%) and rehospitalization in 11 (20%). Discharge to a skilled care facility was required in 5 (9%). At least one preoperative inflammatory marker (WBC, ESR, and CR) was available in 52 (96%) patients, and pre-op albumin was available in 38 (70%). Patients with a WBC >9.6×109/L while on pre-op antibiotic therapy were more likely (RR 1.60) to have culture discordance (93% vs 54%; p=0.019). Patients with pre-op ESR >28.0 mm/h (N=38) while on antibiotic therapy were more likely to have a longer hospital stay (10 days vs 6 days; p=0.007). Patients with a pre-op albumin <3.5g/dl (N=9) were more likely to have a prolonged hospital stay (13 days vs 8 days; p=0.03) or require discharged to skilled care (75% vs 18%, p=0.35). Those with CRP greater than 100.0mg/L had higher rates Clavien grade ≥3 complications (41% vs 11%, p=0.25). ESR >65 mm/h was associated with reintervention for osteomyelitis (83% vs 35%, p=0.36). CONCLUSIONS: Preoperative clinical features including ESR, CRP, WBC, and albumin are associated with an increased risk of morbidity following treatment of USF. Earlier identification of these patients may be useful to ascertain patients who could benefit from further preoperative optimization. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e566 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elizabeth Bearrick More articles by this author Jayson Kemble More articles by this author Samuel Broida More articles by this author Matthew Houdek More articles by this author Boyd Viers More articles by this author Expand All Advertisement PDF downloadLoading ...

MP08-06 OUTCOMES FOR HIGH-RISK BLADDER CANCER AFTER BCG THERAPY IN PATIENTS WITH PRIOR PROSTATE RADIOTHERAPY: A SEER-BASED STUDY

You have accessJournal of UrologyCME1 Apr 2023MP08-06 OUTCOMES FOR HIGH-RISK BLADDER CANCER AFTER BCG THERAPY IN PATIENTS WITH PRIOR PROSTATE RADIOTHERAPY: A SEER-BASED STUDY Adri Durant, Yeonsoo Lee, Lanyu Mi, Faraj Kassem, and Mark Tyson Adri DurantAdri Durant More articles by this author , Yeonsoo LeeYeonsoo Lee More articles by this author , Lanyu MiLanyu Mi More articles by this author , Faraj KassemFaraj Kassem More articles by this author , and Mark TysonMark Tyson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003223.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is evidence that patients with bladder cancer who have previously received radiation therapy (RT) are at increased risk for poorer oncological compared to non-radiated counterparts. Little is known about the impact of prior RT on the efficacy of Bacillus Calmette-Guerin (BCG) in patients with non-muscle invasive bladder cancer (NMIBC). In this context, we investigated the impact of previous prostate RT on 5-year disease progression for NMIBC patients after BCG. METHODS: Male patients with a history of high-risk NMIBC, classified as Ta, T1 and CIS disease with completion of adequate BCG (at least 5 plus 2 treatments), were identified in the Surveillance, Epidemiology, and End Results (SEER) – Medicare database. Patients were stratified into two cohorts based on their history of prior radiation use: RT for prostate cancer prior to bladder cancer diagnosis (NMIBC RT) and no history of prostate cancer radiation (NMIBC without prior RT). The primary endpoint was 5-year total progression defined as progression to systemic chemotherapy, checkpoint inhibitors, radical or partial cystectomy, metastasis or cancer-specific death. Results: In a total of 3442 patients with NMIBC, 3306 had no history of prior RT while 136 had a history of prior RT for prostate cancer. The NMIBC RT cohort varied significantly by age (77.5 v 75.0, p=0.0002) and stage (Ta 43.4%, Tis 19.1%, T1 37.5% v Ta 41.0%, Tis 10.8%, T1 48.2%, p=0.0033) at initial tumor diagnosis. There was no significant difference in risk of progression to chemotherapy (p=0.6469), checkpoint inhibitors (p=0.1096), radical cystectomy (p=0.2023), partial cystectomy (p=0.5613), cancer-specific death (p=0.0667) and 5-year total progression between the two cohorts. On multivariate analysis NMIBC RT patients did not have a significantly higher risk of 5-year total progression (HR 1.37, p=0.08). CONCLUSIONS: In patients with NMIBC who undergo adequate BCG treatment, prior history of pelvic radiation for prostate cancer is not associated with worse progression-free survival. Source of Funding: This study was supported by Grant Number P30 CA015083 from the National Cancer Institute (NCI) and from the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (M.D.T.), the Christian Haub Family Career Development Award for Cancer Research Honoring Dr. Richard Emslander (M.D.T.), and the Eric and Gail Blodgett Foundation (M.D.T.). Its contents are solely the authors' responsibility and do not necessarily represent the official view of the NIH. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e95 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adri Durant More articles by this author Yeonsoo Lee More articles by this author Lanyu Mi More articles by this author Faraj Kassem More articles by this author Mark Tyson More articles by this author Expand All Advertisement PDF downloadLoading ...

Outcomes of Initial Transcorporal Versus Standard Placement of Artificial Urinary Sphincter in Patients With Prior Radiation.

Objective: This study aimed to evaluate both device and functional outcomes of men who underwent initial artificial urinary sphincter (AUS) placement after pelvic radiation using the transcorporal versus the standard approach.Methods: A retrospective review of patients who underwent first-time AUS placement after pelvic irradiation for prostate cancer was conducted between January 2008 and June 2020. Patients were grouped by transcorporal versus standard device placement. The primary outcomes of interest included major complications (revision or explant surgery) and functional outcomes (pads per day, International Prostate Symptom Score {IPSS}, quality of life {QOL} score).Results: We identified 45 patients who underwent first-time AUS with a history of prior pelvic irradiation for prostate cancer, 27 underwent transcorporal placement and 18 underwent standard placement. Transcorporal AUS placement resulted in a significantly lower number of major complications (p=0.01), explants (p=0.02), and revisions (p=0.04) The transcorporal artificial urinary sphincter group had better postoperative pads per day (p=0.04), IPSS (p<0.01), and IPSS QOL score (p<0.01).Conclusions: Initial transcorporal artificial urinary sphincter placement is a promising technique with lower rates of major complications in patients with a history of prior pelvic radiation and had better functional urinary outcomes.

A multicenter, open-label, randomized, phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer

<h3>Objectives:</h3> Results from a phase 1b/2 study showed lenvatinib (LEN) + pembrolizumab (pembro) has efficacy in patients (pts) with advanced endometrial carcinoma following prior treatment. Here, we describe the phase III study results of LEN + pembro vs treatment of physician's choice (TPC) following platinum-based therapy in pts with advanced endometrial cancer (aEC). <h3>Methods:</h3> Pts were randomized (1:1) to receive LEN 20 mg orally QD + pembro 200 mg IV Q3W or TPC (doxorubicin at 60 mg/m² IV Q3W or paclitaxel at 80 mg/m² IV QW [3 weeks on; 1 week off]). Eligible pts had aEC with 1 prior platinum-based chemotherapy regimen or up to 2 prior platinum-based chemotherapy regimens, if 1 was given in the neoadjuvant/adjuvant setting. Randomization was stratified by DNA mismatch repair (MMR) status (centrally determined); pts with proficient (p)MMR tumors were further stratified by ECOG PS, geographic region, and prior history of pelvic radiation. Primary endpoints were PFS by blinded independent central review per RECIST v1.1 and OS. Key secondary endpoints included objective response rate (ORR) and safety. A graphical approach for multiplicity to control for type 1 error was used to test PFS for pts with pMMR aEC, then pts irrespective of MMR tumor status (ie, all comers), followed by OS (pMMR aEC, then all comers) and ORR (pMMR aEC, then all comers). Efficacy analyses were conducted in randomized pts; safety analyses were conducted in pts who received treatment. <h3>Results:</h3> A total of 827 Pts (pMMR, n=697; dMMR, n=130) received LEN + pembro (n=411) or TPC (n=416). Median follow-up was 12.2 mo for pts randomized to LEN + pembro and 10.7 mo for pts randomized to TPC (data cutoff October 26, 2020). PFS was significantly improved with LEN + pembro vs TPC in pMMR aEC (median 6.6 vs 3.8 mo; HR 0.60) and in all-comers (median 7.2 vs 3.8 mo; HR 0.56). OS was significantly longer with LEN + pembro vs TPC in pMMR aEC (median 17.4 vs 12.0 mo; HR 0.68) and in all-comers (median 18.3 vs 11.4 mo; HR 0.62). ORR was significantly greater with LEN + pembro vs TPC in pMMR aEC (30.3% vs 15.1%) and in all-comers (31.9% vs 14.7%). Additional results are in the table. Median treatment duration was 231 days with LEN + pembro and 104.5 days with TPC. Overall, any-grade treatment-emergent adverse events (TEAEs) occurred at similar rates across treatment arms. Grade ≥3 TEAEs occurred in 89% of pts with LEN + pembro and 73% of pts with TPC. In the LEN + pembro arm, 30.8% pts discontinued LEN, 18.7% discontinued pembro, and 14.0% discontinued both study treatments due to a TEAE; the most common TEAEs were hypertension (64%), hypothyroidism (57%), diarrhea (54%) and nausea (50%). <h3>Conclusions:</h3> LEN + pembro demonstrated statistically significant and clinically meaningful improvements in PFS, OS, and ORR vs TPC both in pts with aEC that was pMMR and in pts with aEC irrespective of MMR status. The safety profile of LEN + pembro was manageable and consistent with previously reported studies.

A phase 3 trial evaluating efficacy and safety of lenvatinib in combination with pembrolizumab in patients with advanced endometrial cancer.

TPS5607 Background: Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor receptors 1–3, fibroblast growth factor receptors 1–4, platelet-derived growth factor receptor α, RET, and KIT. Pembrolizumab (PEMBRO) is a monoclonal antibody targeting programmed cell death receptor 1 (PD-1). Preliminary analyses of a phase 1b/2 study of LEN + PEMBRO showed promising antitumor activity and a manageable safety profile in advanced endometrial cancer (EC). Methods: A multicenter, randomized, open-label, phase 3 study (KEYNOTE-775/E7080-G000-309; clinicaltrials.gov NCT03517449) will evaluate efficacy and safety of LEN + PEMBRO vs treatment of physician’s choice (TPC) in patients with advanced EC. Patients must be aged ≥ 18 years, have advanced EC that progressed after 1 prior platinum-based therapy, have measurable disease per RECIST v1.1, and an Eastern Cooperative Oncology Group performance status ≤ 1. Patients must have mismatch repair (MMR) status confirmed by central laboratory via immunohistochemistry on archived or fresh tumor biopsy. ~780 patients (~120 MMR-deficient; ~660 MMR-proficient) will be randomized to receive LEN 20 mg orally once daily and PEMBRO 200 mg intravenously (IV) every 3 weeks (Q3W) or TPC. Patients will be randomized first according to MMR status; MMR-proficient patients will be further stratified by ECOG PS, geographic region, and prior history of pelvic radiation. TPC is either doxorubicin 60 mg/m2 by IV Q3W or paclitaxel 80 mg/m2 by 1-hour IV infusion weekly (3 weeks on/1 week off). The dual primary endpoints are progression-free survival (PFS; per RECIST v1.1 by blinded independent central review) and overall survival (OS). The PFS analysis will occur at the planned interim analysis (~363 OS events in MMR-proficient patients; ~524 PFS events), and the study will have 99% power to detect a hazard ratio (HR) of 0.55 with a 1-sided 0.0005 significance level. A final OS analysis will occur at 518 OS events, when the study will have 90% power to detect a HR of 0.75 with a 1-sided 0.0245 significance level. Secondary endpoints include objective response rate, health-related quality of life, safety and tolerability, and pharmacokinetics. Clinical trial information: NCT03517449.

Treatment of primary rectal adenocarcinoma after prior pelvic radiation: The role of hyperfractionated accelerated reirradiation

PurposePrevious studies have reported that hyperfractionated accelerated reirradiation can be used as part of multimodality treatment of locally recurrent rectal cancer with acceptable toxicity and promising outcomes. The purpose of this study was to evaluate the outcomes and toxicity of hyperfractionated accelerated reirradiation for patients with primary rectal adenocarcinoma and a history of prior pelvic radiation for other primary malignancies. Methods and materialsWe identified 10 patients with a prior history of pelvic radiation for other primary malignancies who were treated with hyperfractionated accelerated reirradiation for primary rectal adenocarcinoma. Radiation therapy was administered with 1.5 Gy twice daily fractions to a total dose of 39 Gy to 45Gy. ResultsThe median follow-up time was 3.2 years (range, 0.6-9.0 years). Seven of 10 patients received surgery after reirradiation. The 3-year freedom-from-local-progression rate was 62% for all patients and 80% for patients who underwent surgery. The 3-year overall survival rate was 100%, with 3 deaths occurring at 4.7, 6.5, and 9.0 years after reirradiation. One patient had an acute Grade 3 toxicity of diarrhea, and 1 patient experienced a late Grade 3 toxicity of sacral insufficiency fracture. ConclusionsHyperfractionated accelerated reirradiation was well tolerated with promising rates of freedom from local progression and overall survival in patients with primary rectal cancer with a history of prior pelvic radiation therapy. This approach, along with concurrent chemotherapy and surgery, appears to be a viable treatment strategy for this patient population.

MP46-07 MULTICENTER ANALYSIS OF ARTIFICIAL URINARY SPHINCTER OUTCOMES IN PATIENTS AFTER BOTH RADICAL PROSTATECTOMY AND ANASTOMOTIC URETHROPLASTY

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy1 Apr 2017MP46-07 MULTICENTER ANALYSIS OF ARTIFICIAL URINARY SPHINCTER OUTCOMES IN PATIENTS AFTER BOTH RADICAL PROSTATECTOMY AND ANASTOMOTIC URETHROPLASTY Jonathan Wingate, Jeremy Myers, Gregory Murphy, Nejd Alsikafi, Bradley Erickson, Benjamin Breyer, and Bryan Voelzke Jonathan WingateJonathan Wingate More articles by this author , Jeremy MyersJeremy Myers More articles by this author , Gregory MurphyGregory Murphy More articles by this author , Nejd AlsikafiNejd Alsikafi More articles by this author , Bradley EricksonBradley Erickson More articles by this author , Benjamin BreyerBenjamin Breyer More articles by this author , and Bryan VoelzkeBryan Voelzke More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1446AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We sought to assess artificial urinary sphincter (AUS) outcomes in a subset of patients who have had a history of radical prostatectomy and anastomotic urethroplasty in order to describe outcomes after having two prior urethral transecting surgeries. Our null hypothesis is that multiple transections of the urethra do not increase the possibility of urethral erosion following artificial urinary sphincter placement. METHODS We performed a retrospective review from five participating centers in the Trauma and Urologic Reconstruction Network of Surgeons. The study period included February 2010 - January 2016. Of the 445 incontinence procedures in our prospective database, there were 35 patients who underwent an AUS and had both a radical prostatectomy and anastomotic urethroplasty. Patients were excluded if they did not have a minimum of 6 months of follow up after AUS placement. Twenty-two patients met inclusion criteria. The surgeon independently determined choice of transcorporal or standard cuff technique. RESULTS Median age was 67.5 years. Mean follow up time was 32.2 months (IQR 16.6 - 44.6 months). Twelve patients had a history of prior pelvic radiation for prostate cancer. Of the 22 patients, twenty patients had transcorporal cuff placement. There were 7 complications - 2 erosions, 3 hematomas, 1 infection, and 1 pump migration. Of these complications, four required additional surgery - the two erosions underwent AUS removal, one hematoma required exploration, and the patient with pump migration had his pump location adjusted. The overall AUS in situ rate in our cohort was 90.9% (20/22). History of prior radiation was not associated with AUS complications (p = 0.23). CONCLUSIONS AUS implantation can be performed in patients after two urethral transecting surgeries with an in situ rate of 90.9% at medium term follow up. Surgeons appear to prefer transcorporal placement in these scenarios. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e621 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Jonathan Wingate More articles by this author Jeremy Myers More articles by this author Gregory Murphy More articles by this author Nejd Alsikafi More articles by this author Bradley Erickson More articles by this author Benjamin Breyer More articles by this author Bryan Voelzke More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Proton Therapy for Vaginal Reirradiation.

Primary or recurrent gynecologic cancers in operable patients with a history of prior pelvic radiation are typically treated with surgery based on the risk of late toxicities historically associated with reirradiation. A number of studies have demonstrated that, compared with conventional radiation therapy (RT) using photons, proton therapy (PT) offers dosimetric advantages for patients with gynecologic cancers by reducing radiation dose to healthy tissues. Thereby, we expect that, in appropriately selected cases, PT may reduce long-term treatment-related morbidities without compromising treatment efficacy. Herein, we describe the treatment planning, technique, and long-term follow-up of a patient who was treated with PT for a primary vaginal carcinoma nearly 30 years after a prior course of pelvic RT. Using this case, we illustrate the utility and advantages of PT in the treatment of cancers that occur at less favorable sites, adjacent to normal structures with low radiation tolerance, or in paients with a history of prior irradiation. Additionally, we provide a brief discussion and review of literature of prior case series of pelvic reirradiation, illustrating the value of identifying treatment approaches that can reduce treatment-related morbidities, particularly late treatment toxicities.

MP15-06 BIPOLAR INCISION OF BLADDER NECK CONTRACTURE WITH INTRALESIONAL INJECTION OF MITOMYCIN C: A SINGLE INSTITUTION EXPERIENCE

INTRODUCTION AND OBJECTIVES: Transurethral incision of bladder neck contracture (TUIBNC) has high failure rates, prompting concomitant injection of a scar modulator. We present our single institution series of bipolar TUIBNC with immediate mitomycin C (MMC) injection to determine if the combination therapy could improve patency rates. METHODS: Records for all patients who underwent TUIBNC with intralesional MMC at a single institution from 2013e2014 were retrospectively reviewed. Instruments used were the biopolar Gyrus ACMI PK button electrode or PK Plasma-CISE . A total of 2mg of 40% mitomycin C solution was injected in four quadrants of the treated BNC. Postoperatively, patients were monitored for stricture recurrence using a combination of serial postvoid residuals, uroflowometry and flexible cystoscopy. Failure was defined as the need for subsequent intervention. RESULTS: Fifteen patients underwent bipolar TUIBNC with MMC. All were Caucasian males with a median age of 66 years (IQR 6). Etiologies included radical prostatectomy (8), transurethral prostate resection (3), radical cystoprostatectomy (2), and prostate brachytherapy (2). Fourteen (93%) patients had failed at least one prior intervention. Overall, 7 (47%) patients recurred following an initial TUIBNC with MMC at a median follow up of 9.9 months (IQR 9.2). Six of the 7 chose to undergo repeat TUIBNC with MMC, 2 (33%) of whom recurred during median follow up of 7 months (IQR 11). Likelihood of BNC recurrence was not significantly associated with history of prior pelvic radiation (33% vs 56%, p 1⁄4 0.4). Two patients experienced a postoperative complication but no serious adverse events occurred. CONCLUSIONS: Bipolar TUIBNC with MMC injection had lower than expected efficacy with a 10-month failure rate near 50%.

Use of desipramine for the treatment of overactive bladder refractory to antimuscarinic therapy.

To evaluate the use of desipramine in the treatment of overactive bladder (OAB). We retrospectively evaluated 43 patients who were treated with desipramine for OAB refractory to antimuscarinic therapy. These OAB patients were stratified by the presence or absence of bladder pain. Forty-three patients were evaluated with a mean follow up time of 12.2 ± 4.6 months. The mean age of the patients was 71 ± 16 years. Twelve patients (28%) discontinued desipramine, 9 due to perceived lack of efficacy, 2 due to central anticholinergic side effects, and 1 due to the development of oropharyngeal sores. Patients were stratified into two subgroups based upon treatment with desipramine for OAB alone (n = 29) or OAB and bladder pain (n = 14). There was no difference between the groups in regard to sex (P = .34), prior history of radiation (P = .19), side effects (P = .16), and specifically evaluated central anti-cholinergic side effects (P = .66). There was no statistical difference in the self-reported success rate of the medication (P = .48). In the OAB plus bladder pain subgroup, 71% of patients reported improvement in their pain. Overall, 13 (30%) patients had history of prior pelvic radiation and 10 of those (77%) reported improvement with desipramine. Desipramine is a potential useful treatment for patients with OAB. In addition, it can be used in patients with OAB and bladder pain and patients with complex OAB such as OAB caused by pelvic radiation.

Reirradiation for Cancers of the Rectum and Anal Canal

The purpose of this study is to retrospectively determine freedom from progression, overall survival and toxicity in patients with a prior history of pelvic radiation who were treated with re-irradiation for rectal and anal cancers.

Slings for Stress Urinary Incontinence in Men: An Update

Stress urinary incontinence is usually caused by iatrogenic injury during prostate cancer surgery. Most treatment options are surgical in nature and include periurethral bulking, artificial urinary sphincter, and male slings. During the past decade, innovations in male sling surgery have contributed to an increased interest in their use among treating urologists and their patients. Currently, male slings are most efficacious in men with mild to moderate stress incontinence, with no prior history of pelvic radiation, and without prior artificial sphincter placement. In this population, high efficacy rates and low complication rates are typically achieved.

Vaginal intraepithelial neoplasia: A retrospective analysis of clinical features and colpohistology

To analyze the clinical features and colpohistology of women with vaginal intraepithelial neoplasia (VAIN). Patients with VAIN treated at Rajavithi Hospital between April 1986 and October 2007. Of 68 patients, 52.9% had VAIN2/3. The mean age of patients was 50.85 +/- 13.17 years (range: 22-80). The most common presentation was abnormal cytology. History of prior pelvic radiation, associated neoplasia of the lower genital tract and history of prior hysterectomy were documented in 7.4, 67.6 and 54.4% of patients, respectively. Median intervals from previous lower genital tract neoplasia to current diagnosis of VAIN, and between hysterectomy to diagnosis of VAIN were 23.9 and 29.7 months, respectively. The upper third of the vagina was the most common site of VAIN (86.8%). The most common colposcopic finding was the presence of acetowhite epithelium. Punctation was significantly associated with VAIN2/3 (P < 0.05). Mosaic was rare and found in VAIN3. VAIN can occur at any age and is commonly associated with neoplasia of the lower genital tract. Most patients have disease located in the upper third of the vagina. The most common colposcopic finding is acetowhite epithelium while punctation and mosaic pattern are more prevalent in VAIN2/3.

A SARC multicenter phase III study of gemcitabine (G) vs. gemcitabine and docetaxel (G+D) in patients (pts) with metastatic soft tissue sarcomas (STS)

9514 Background: We sought to compare the response of metastatic STS to G vs. G+D in a phase III study using a novel Bayesian adaptive randomization strategy. Methods: Entry criteria included non-GIST STS diagnosis, age &gt; 10, measurable disease, ≤ 3 prior regimens, normal organ function, and Grade (Gr) ≤ 1 neuropathy. Pts were stratified by histology (leiomyosarcoma [LMS] vs. other), and history of prior pelvic radiation (PPR) or not, yielding 4 diagnostic subgroups. Therapy was G 1200 mg/m2 (over 120 min, d1+d8) or G 900 mg/m2 (over 90 min, d1+d8) and docetaxel (100 mg/m2 d8) q21d; all pts received (peg)-filgrastim starting d9. 25% dose reductions were employed for PPR or toxicity. The primary endpoint was tumor response (CR, PR, or 24+ weeks stable), using a double-blind Bayesian adaptive randomization procedure to incrementally assign more pts to the superior treatment arm, while accounting for possible treatment-subgroup interactions. Although this study is not based on a 1:1 randomized phase III design, enrolling ∼120 pts would show a difference between a response rate (RR) of 10% for G and 30% with G+D with a power of 0.8 and two-sided alpha of 0.05. Results: 122 pts were randomized; 119 pts had evaluable outcomes. Median number of prior regimens was 1; median number of cycles was 4 (range 1–26). 49 pts were adaptively randomized to G and 73 to G+D, indicating superiority of G+D. Of 119 evaluable pts, 27% (G) and 32% (G+D) showed response as defined. The odds of pts with LMS receiving G+D instead of G increased from 1:1 at the start of the study to ∼6:1 at its completion. RR was 10% (G) vs. 16% (G+D) (p=0.15, Fisher exact test). Consistent with the RR outcomes, progression free survival (PFS) was 6.2 m (G+D, K-M 95%CI 3.6–8.8) vs. 2.6 m (G, 95%CI 2.0–3.2). Overall survival (OS) was 18.0 m (G+D, K-M 95%CI 11.7–24.1) vs. 11.2 m (G, 95%CI 6.8–15.5). Pts receiving G+D had a higher rate of discontinuation due to toxicity than those receiving G (p&lt;0.01, log rank). Conclusions: We observed substantial clinical activity in this pre-treated STS population. G+D yields superior PFS and OS to G, but at the price of increased toxicity. Adaptive randomization is an effective method that substantively reduces the number of pts receiving inferior therapy. [Table: see text]

Complications of cystectomy in patients with a history of pelvic radiation

Objectives. To compare the complications occurring during the first year of follow-up after radical cystectomy in two groups, one with and one without a history of pelvic radiation. Radical cystectomy and urinary diversion is the treatment of choice for invasive bladder cancer. Methods. One hundred ninety-four cystectomies were performed between January 1995 and June 2000 by a single surgeon. Twenty-three patients were identified with a history of external beam radiotherapy to the pelvis (EBRT group), and 23 additional patients without a history of pelvic radiation were randomly selected to serve as the control group. Results. Although the overall risk of having a complication was not statistically different in the EBRT group (48%) than in the control group (30%; P = 0.183), complications directly related to surgery were higher in the EBRT group than in the control group (48% versus 26%; P = 0.045). The patients in the EBRT group were more likely to require an invasive procedure (39% versus 9%; P = 0.018). In addition, 5 (22%) of 23 patients in the EBRT group had a symptomatic fluid collection, which was diagnosed as a urine leak (n = 2) or an abdominal abscess (n = 3). In contrast, no patient in the control group developed a symptomatic fluid collection. Conclusions. Cystectomy after pelvic radiation is associated with acceptable morbidity; however, compared with cystectomy performed in a nonirradiated pelvis, the risk of complications that will require invasive intervention is increased. A history of prior pelvic radiation significantly increases the risk of a symptomatic fluid collection.

Management of Early and Late Complications of Ileocolonic Continent Urinary Reservoir (Miami Pouch)

Abstract Purpose. The object of this study is to review our experience and formulate a plan for early recognition and effective management of early and late complications seen in patients who have undergone construction of the ileocolonic continent urinary reservoir. Method. Charts of patients who underwent continent urinary diversion at the Division of Gynecologic Oncology, University of Miami School of Medicine, from 1988 to 1996 were reviewed. We analyzed our data in terms of early and late (beyond 6 weeks) complications resulting directly from the operation or from this form of urinary diversion. Results. Urinary diversion via the continent ileocolonic reservoir has been performed at our institution since February 1988. Sixty-six women have undergone construction of the Miami pouch over the past 81 years. Sixty-three of 66 patients needed a reservoir as a part of total pelvic exenteration for persistent or recurrent gynecologic malignancy. Three patients underwent reservoir construction for repair of vesicovaginal fistula. Sixty-two of 66 patients (95%) have a history of prior pelvic radiation. A total of 35 patients (53%) suffered early complications resulting in an operative mortality rate of 9% (6 of 66 patients). Early complications related to the construction of the reservoir included ureteral stricture/obstruction [10], anastomotic leak [4], reservoir-cutaneous fistula [4], difficulty in catheterization [5], pyelonephritis [10], sepsis [6], DIC [2], and ARDS [1]. Nonsurgical management strategies used for reservoir-related complications in these cases included percutaneous nephrostomy, peripheral hyperalimentation, intravenous antibiotics, and ultrasound-guided catheter placement. Eighty-four percent (16/19) of functional complications of the reservoir resolved with conservative management, whereas 3/19 patients needed surgical revision. One or more late complications (beyond 6 weeks) occurred in 25 patients (37%). Late complications seen included ureteral stricture/obstructions [6], incontinence [8], difficulty in catheterization [7], and urinary stones [4]. Nonsurgical management strategies used included percutaneous nephrostomy, balloon dilation, scheduled catheterization, ultrasound-guided catheter placement, and endoscopic/percutaneous lithotripsy. Four of 25 patients needed reoperation, whereas in 84% (21/25) of patients problems resolved with initial conservative management. Conclusion. Successful conservative therapy constitutes establishment of drainage, adequate nutrition, avoidance of sepsis, close observation, and patience. This article reviews the complications of the continent ileocolonic form of urinary diversion and formulates a treatment outline emphasizing an initial conservative approach that offers optimal management of early and late complications seen in this patient group.

Management of Early and Late Complications of Ileocolonic Continent Urinary Reservoir (Miami Pouch)

Purpose.The object of this study is to review our experience and formulate a plan for early recognition and effective management of early and late complications seen in patients who have undergone construction of the ileocolonic continent urinary reservoir.Method.Charts of patients who underwent continent urinary diversion at the Division of Gynecologic Oncology, University of Miami School of Medicine, from 1988 to 1996 were reviewed. We analyzed our data in terms of early and late (beyond 6 weeks) complications resulting directly from the operation or from this form of urinary diversion.Results.Urinary diversion via the continent ileocolonic reservoir has been performed at our institution since February 1988. Sixty-six women have undergone construction of the Miami pouch over the past 81 years. Sixty-three of 66 patients needed a reservoir as a part of total pelvic exenteration for persistent or recurrent gynecologic malignancy. Three patients underwent reservoir construction for repair of vesicovaginal fistula. Sixty-two of 66 patients (95%) have a history of prior pelvic radiation. A total of 35 patients (53%) suffered early complications resulting in an operative mortality rate of 9% (6 of 66 patients). Early complications related to the construction of the reservoir included ureteral stricture/obstruction [10], anastomotic leak [4], reservoir-cutaneous fistula [4], difficulty in catheterization [5], pyelonephritis [10], sepsis [6], DIC [2], and ARDS [1]. Nonsurgical management strategies used for reservoir-related complications in these cases included percutaneous nephrostomy, peripheral hyperalimentation, intravenous antibiotics, and ultrasound-guided catheter placement. Eighty-four percent (16/19) of functional complications of the reservoir resolved with conservative management, whereas 3/19 patients needed surgical revision. One or more late complications (beyond 6 weeks) occurred in 25 patients (37%). Late complications seen included ureteral stricture/obstructions [6], incontinence [8], difficulty in catheterization [7], and urinary stones [4]. Nonsurgical management strategies used included percutaneous nephrostomy, balloon dilation, scheduled catheterization, ultrasound-guided catheter placement, and endoscopic/percutaneous lithotripsy. Four of 25 patients needed reoperation, whereas in 84% (21/25) of patients problems resolved with initial conservative management.Conclusion.Successful conservative therapy constitutes establishment of drainage, adequate nutrition, avoidance of sepsis, close observation, and patience. This article reviews the complications of the continent ileocolonic form of urinary diversion and formulates a treatment outline emphasizing an initial conservative approach that offers optimal management of early and late complications seen in this patient group.