bluuebunny/crossref_metadata_2025 huggingface dataset:
PSA status after neoadjuvant androgen deprivation therapy before high-dose-rate brachytherapy as biomarker for prediction of long-term outcome in high-risk prostate cancer patients.
Authors: Wedde Trude , Cvancarova Milada , Hayman Jonathan S. , Tran Phuoc T. , Tafjord Gunnar , DeWeese Theodore L. , Lilleby Wolfgang
Published: February 2020

301

Background: The aim is to investigate the clinical significance of biochemical response after Androgen Deprivation Therapy (ADT) prior to high-dose-rate brachytherapy (HDR-BT) for early identification of patients at increased risk of recurrence. Measured outcomes included biochemical relapse free survival (bRFS), distant metastasis free survival (DMFS) and overall survival (OS). Methods: A total of 324 patients with high-risk Prostate Cancer (PCa) were identified in the Norwegian Radium Hospital brachytherapy database. Neo-adjuvant ADT was administered for 3-6 months, followed by two 10 Gy HDR-BT treatments to the prostate, each spaced by two weeks, followed by conformal external beam radiation to 50 Gy to the prostate gland and seminal vesicles. Total length of ADT ranged from 12 to 36 months. PSA (ng/mL) and testosterone values (T, nmol/L) after 3-6 months of neo-adjuvant ADT were measured. Kaplan Meier and Cox regression analyses were performed. Results: Median age at diagnosis was 66 years and median follow-up was 10 years. At last follow-up, 277 patients (85,2%) were alive, 10 patients (3.1%) had died of prostate cancer and 37 patients (11.4%) died of other causes. 24 patients (7.4%) had biochemical relapse and 9 patients (2.8%) had distant metastasis within the first 5 years. Patients with PSA > 1 after neo-adjuvant therapy had 4.3 (95%CI 1.7 to 11.1) higher odds of biochemical relapse within 5 years compared to patients with PSA < 1 (p = 0.002). ROC analysis confirmed that PSA < 1 had a prediction accuracy of 0.76 (sensitivity 68% and specificity 67%). T < 0.7 and PSA < 1 after neo-adjuvant therapy were associated with improved bRFS, DMFS and OS (p < 0.001). Neither the length of neo-adjuvant nor total ADT treatment impacted outcomes (p > 0.05). Conclusions: Dose intensification with 2 HDR-BT boosts resulted in excellent survival in our cohort. PSA > 1 after neo-adjuvant ADT may be able to predict patients at increased risk of relapse and worse OS and identify patients in whom increased monitoring and/or intervention is warranted. ADT > 1 year did not improve outcome, indicating that shorter course of ADT may be used.
Deep learning using preoperative MRI information to predict early recovery of urinary continence after robot-assisted radical prostatectomy.
Authors: Sumitomo Makoto , Teramoto Atsushi , Fukami Naohiko , Fukaya Kosuke , Zennami Kenji , Ichino Manabu , Takahara Kiyoshi , Kusaka Mamoru , Shiroki Ryoichi
Published: February 2020

310

Background: Urinary incontinence remains one of the most bothersome postoperative complications even after robot-assisted radical prostatectomy (RARP). We aimed to make a novel prediction system that can be used preoperatively to inform patients of the accuracy of early recovery of urinary continence after RARP using a deep learning (DL) model from magnetic resonance imaging (MRI) information and preoperative clinicopathological parameters. Methods: A retrospective cohort study was conducted on prostate cancer (PC) patients who had undergone RARP at our hospital between August 2015 and July 2019. Patients using no pads/no leakage of urine or the use of a safety pad within 3 months after RARP is categorized into “good” continence and others into “no good” continence. MRI DICOM data from axial, coronal and sagittal imaging as well as preoperative clinicopathological covariates (age, BMI, prostate volume, serum PSA level, Gleason score, clinical stage) were assessed. Supervised DL algorithms, which included AdaBoost, Naive Bayes, Neural Network, Random Forest, and SVM were trained and tested as binary classifiers (good or no good). To evaluate the DL models from the testing data set, their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), as well as area under the receiver operating characteristic curve (AUC) were analyzed. Results: Data were available for 497 patients in the study period. The AdaBoost DL algorithm using MRI information in addition to clinicopathological parameters had the highest performance with sensitivity at 92%, specificity at 77%, PPV at 79%, NPV at 91%, and AUC at 84% for predicting good continence, while that using clinicopathological parameters only had the performance with sensitivity at 50%, specificity at 69%, PPV at 60%, NPV at 60%, and AUC at 60%. Conclusions: Our results suggest that the DL algorithms using MRI imaging information are highlighted as an accurate method for strongly predicting early recovery of urinary continence after RARP. Thus, DL predictions may help allocation of treatment strategies for PC patients who dislike prolonged urinary incontinence after RARP.
Impact of somatic SPOP (Speckle-Type POZ protein) mutation (mtSPOP) on response to systemic therapy and survival outcome in men with de novo metastatic castration-sensitive prostate cancer (d-mCSPC).
Authors: Swami Umang , Isaacsson Velho Pedro , Nussenzveig Roberto , Sacristan Santos Victor , Erickson Stephanie , Dharmaraj Divya , Alva Ajjai Shivaram , Vaishampayan Ulka N. , Esther John , Hahn Andrew W , Maughan Benjamin Louis , Antonarakis Emmanuel S. , Agarwal Neeraj
Published: February 2020

329

Background: Men with metastatic castration resistant prostate cancer harboring somatic mutant SPOP (mt SPOP) have improved progression free survival (PFS) on abiraterone than those with wild-type SPOP (wt SPOP) (Boysen et al, CCR 2018; PMID: 30068710). We hypothesized that mtSPOP will be associated with improved response to systemic therapy and outcomes in mCSPC. Methods: This retrospective study included patients from 4 academic institutions. Eligibility criteria: receipt of standard androgen deprivation therapy (ADT) without intensification (chemotherapy or novel hormonal agents) for the diagnosis of d-mCSPC, no prior history or treatment for prostate cancer, and established SPOP status determined by targeted next-generation sequencing. PFS was defined per PCWG2 defined PSA or investigator assessed radiographic progression. Overall survival (OS) was calculated from date of starting ADT for d-mCSPC to date of death. Kaplan-Meier analysis and t-test were used to compare variables in these two cohorts. Results: Of 110 mtSPOP men with advanced prostate cancer identified, 37 had d-mCSPC of which 25 received ADT. Of 353 wtSPOP patients, 184 had d-mCSPC of which 97 received ADT. Baseline demographics and disease characteristic were similar (table). mtSPOP was associated with significantly improved PFS [35 vs. 14 months, HR 0.519 (95% CI 0.312-0.861), p=0.011] and OS [97 vs. 69 months, HR 0.4392 (95% CI=0.207-0.931); p=0.032] with ADT as compared to wtSPOP patients. Conclusions: Men with d-mCSPC with somatic mtSPOP have improved outcomes with ADT than those with wtSPOP. Once validated, these hypothesis generating data may aid with counselling and treatment selection, as well as patient stratification in future trials in d-mCSPC.[Table: see text]
Concordance between MRI fusion versus TRUS prostate biopsy and final pathology at radical prostatectomy: Data from the PURC.
Authors: Talwar Ruchika , Michel Katharine , Malhotra Aseem , Fonshell Claudette , Danella John , Ginzburg Serge , Lanchoney Thomas , Raman Jay D. , Reese Adam , Tomaszewski Jeffrey , Trabulsi Edouard John , Smaldone Marc C. , Uzzo Robert Guy , Lee Daniel , Guzzo Thomas J.
Published: February 2020

354

Background: Studies suggest that MRI-fusion guided biopsies are superior to the transrectal ultrasound guided (TRUS) technique. Herein, we present the Pennsylvania Urologic Regional Collaborative (PURC) experience with MRI fusion biopsy. We aimed to calculate concordance rates between TRUS prostate needle biopsy versus MRI fusion biopsy and final pathology at the time of radical prostatectomy within our cohort. Methods: Within PURC, a prospective quality improvement collaborative of urology practices in Pennsylvania and New Jersey, we identified all men who underwent a TRUS or MRI fusion prostate needle biopsy followed by radical prostatectomy for the treatment of prostate cancer from 2015 to 2018. We analyzed International Society of Urological Pathology Grade Group (GG) scoring and calculated the concordance and upgrading rates at the time of biopsy versus final pathology at radical prostatectomy. To assess for differences between our rates, we performed a test of equal proportions and Pearson's chi-squared test (significance = p<0.05). Results: We identified 1,437 men who underwent TRUS (n=1247) or MRI Fusion (n=196) biopsies followed by radical prostatectomy. Overall pathologic grading distribution at time of biopsy was: 35.8% (n=515) Grade Group (GG) 1, 28.5% (n=409) GG 2, 13.3% (n=191) GG 3, 11.5% (n=165) GG 4, and 10.9% (n=157) GG 5. Median number of cores at TRUS biopsy was 12 (IQR: 12,13). Median number of cores at MRI Fusion biopsy was 15 (IQR 13,18). Therefore, we inferred patients who underwent MRI Fusion biopsy also underwent standard TRUS biopsies at that time. On average, exact concordance rate between MRI Fusion biopsy and final pathology was 9.1% higher than concordance rate of TRUS biopsy (44.4% vs 35.3%, 95% CI: 1.6%-16.5%, p < 0.01). The overall rate of upgrading on final pathology for MRI fusion biopsies was 5.7% lower than for TRUS biopsies, but this was not statistically significant (35.2% vs 40.9%, 95% CI: 1.5-13.0%, p=0.06). Conclusions: MRI fusion biopsies demonstrated higher concordance rates with final pathology at the time of radical prostatectomy than TRUS prostate biopsies alone.
The relationship between socioeconomic status and treatment for prostate cancer in a universal healthcare system: A population-based analysis.
Authors: Oake Justin , Harasemiw Oksana , Tangri Navdeep , Ferguson Thomas , Saranchuk Jeff W. , Bansal Rahul K. , Drachenberg Darrel , Nayak Jasmir G.
Published: February 2020

361

Background: A large body of research has shown that there are strong socioeconomic disparities in access to cancer treatment. However, whether these inequalities persist among men with prostate cancer has not been previously explored in the equal-access, universal Canadian health care system. The aim of this study is to compare whether socioeconomic status is associated with the type of treatment received (radical prostatectomy (RP) versus radiation therapy (RT)) for men diagnosed with nonmetastatic prostate cancer in Manitoba, Canada. Methods: Men who were diagnosed with non-metastatic prostate cancer between 2004 and 2016 and subsequently treated with RP or RT were identified using the CancerCare Manitoba Registry and linked to provincial databases. SES was defined as neighbourhood income by postal code and divided into income quintiles (Q1-Q5, with Q1 the lowest quintile and Q5 the highest). Multivariable logistic regression nested models were used to compare whether socioeconomic status was associated with treatment type received. Results: We identified 4,560 individuals between 2004-2016 who were diagnosed with non-metastatic prostate cancer. 2,554 men were treated with RP and 2,006 with RT.As income quintile increased, men were more likely to undergo RP than RT (Q3 vs Q1: aOR 1.45 (1.09-1.92); Q5 vs. Q1: aOR 2.17, 95% CI 1.52-2.86). Conclusions: Despite a universal health care system, socioeconomic inequities are present for men seeking primary treatment for prostate cancer. Further investigation into the decision making process among patients diagnosed with prostate cancer may inform decision making to ameliorate these disparities.
Redefining the role of adjuvant versus salvage radiation therapy for prostate cancer after radical prostatectomy for T3 disease and/or positive margins.
Authors: Goy Barry W. , Liu In-Lu Amy
Published: February 2020

367

Background: SWOG 8794 recommends adjuvant radiation therapy (ART) after radical prostatectomy (RP) for T3 and/or positive margins. Our purpose was to assess 12-year outcomes on 862 RP patients who had either T3 and/or positive margins who underwent surveillance, salvage radiation therapy (SRT), or hormonal therapy (HT), while categorizing these patients into very low risk (VLR), low risk (LR), high risk (HR), and ultra high risk (UHR) groups. Methods: From 2004 - 2007, 862 RP patients had adverse factors of extracapsular penetration (T3a), seminal vesicle invasion (T3b), positive margins, and/or detectable post-operative PSA. Management included surveillance (54.8%), SRT (36.8%), and HT (8.5%) as first salvage therapy, and 21.5% eventually received hormonal therapy. Twenty patients underwent ART, and were excluded from this analysis. We assessed prognostic factors using multivariable analysis, and 12-year estimates of freedom from biochemical failure (FFBF), freedom from salvage therapy (FFST), distant metastases-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS). VLR were those with Gleason Score (GS) of 6. LR were GS 3+4 with only T3a or positive margins, but an undetectable postoperative PSA <0.1. HR were T3b with GS 7-10, any GS 7-10 with T3a/b and positive margins, but an undetectable PSA. UHR were those with a detectable PSA with a GS 7-10. Results: Median follow-up was 12.1 years. Median age was 61.6 years. Median time to first salvage treatment for VLR, LR, HR, and UHR were 10.8, 11.1, 5.3, and 0.6 years, p<0.001. 12-year estimates of FFBF for VLR, LR, HR, and UHR were 60.2%, 52.9%, 28.4%, and 0%, p<0.0001. For FFST, 70.9%, 68.6%, 40.5%, and 0%, p<0.0001. For DMFS, 99.1%, 97.8%, 88.6%, and 63.6%, p<0.0001. For PCSS, 99.4%, 99.5%, 93.5%, and 78.9%, p<0.0001. For OS, 91.8%, 91.8%, 81.0%, and 69.9%, p<0.0001. Conclusions: Outcomes of T3 and/or positive margins using surveillance or SRT as initial management yields excellent outcomes for VLR and LR groups, in which ART should be avoided. For HR, ART can be considered reasonable, since FFBF is only 28.4%. For VHR, these patients may benefit from combined hormonal therapy and ART.
PIVOTALboost Trial contouring RTQA.
Authors: Syndikus Isabel , Tree Alison , Staffurth John , Mayles Helen , Naismith Olivia Frances , Montazeri Amir , Hall Emma
Published: February 2020

373

Background: The PIVOTALboost trial (ISRCTN80146950) recruits patients with intermediate and high risk, localised prostate cancer; it tests the role of pelvic node radiotherapy and the effectiveness of a focal intra-prostate IMRT boost. Prior to opening to recruitment a contouring QA program was designed aiming to improve consistency in clinical outlining. Methods: Intra-prostatic boosting was a new treatment method for all but 3 trial centers. Guidelines for boost contouring and pelvic node outlining were circulated. Clinicians were sent two different cases with the clinical case description, biopsy details, the diagnostic pre-biopsy multi-parametric MRI (T2W and DWI sequences) and planning CT and MRI scans. They were asked to contour prostate, seminal vesicle (CTVp, CTVpsv), lymph node (CTVn) for 1 case and boost volume (GTVpb) for both cases. The 3 lead trial clinicians contoured the cases independently, agreed on gold standard outlines and criteria for failing the submission. Center’ benchmark case submissions were reviewed and standardized feedback forms returned to each clinician. General issues were addressed during a trial launch workshop. Results: There was good agreement of the contours for CTVp, CTVpsv and CTVn between the 3 lead clinicians for the gold standard; more discussions were required to agree GTVpb. Criteria for re-submission were: contours >6mm beyond or >3mm inside the superior and inferior level, included OARs, excluded SV base or extracapsular extension. In addition, for GTVpb, the wrong segment, extension outside CTVp, outlining abnormalities <5mm in diameter or a volume > or < 50% of the gold standard. 35 center and 54 clinicians submitted outlines: for CTVp/psv 24/54 failed, CTVn 14/54 failed, GTVpb 23/48 failed (6 investigators did not submit a volume). All center passed the re-submission; for the on trial outlining review, 9 centres have not recruited a patient for the on trial review process, 18 passed and 8 failed. Conclusions: Errors and inconsistencies were common in the benchmark outlining exercises for the trial. Individual feedback, guidelines and clinical support has reduced outlining variations without delaying the opening of the trial; it has helped to standardize contouring and engage clinicians in the trial process. Clinical trial information: 80146950.
Benefit of prophylactic anticoagulation before and during first-line chemotherapy on patients with metastatic germ cell tumors.
Authors: Fankhauser Christian Daniel , Tran Ben , Ruiz Morales Jose Manuel , Gonzalez-Billalabeitia Enrique , Seidel Christoph Alexander , Bokemeyer Carsten , Hermanns Thomas , Rumyantsev Alexey , Goncalves Margarida Brito , Flechon Aude , Kwan Edmond Michael , Castellano Daniel , Garcia del Muro Xavier , Hamid Anis , Ottaviano Margaret , Reid Alison Helen , Bedard Philippe L. , Sweeney Christopher , Connors Jean M.
Published: February 2020

402

Background: Recent trials randomising patients (pts) receiving systemic cancer therapy showed that prophylactic anticoagulation (PAK) halves the risk of venous thromboembolic events (VTE) and doubles the risk of bleeding (Khorana et al. & Carrier et al., both NEJM 2019). In pts with metastatic germ cell tumors (mGCT) VTE is a frequent complication but it remains unclear whether PAK should be recommended because the number of mGCT pts in those trials was small. We aimed to determine the risk of VTE before, during and after chemotherapy and in mGCT pts without and with risk factors for VTE (retroperitoneal lymph nodes, Khorana score, venous access device) and to calculate the number needed to treat (NNT) and number needed to harm (NNH) of PAK. Methods: This retrospective analysis included mGCT pts treated with first-line platinum-based chemotherapy. We excluded patients who received PAK, with a known history of coagulopathy or VTE and extracted data about VTE and bleeding events. Cumulative VTE incidence was calculate for patients without and with increasing number of known risk factors for VTEs. NNT and NNH were calculated by assuming similar hazard ratios (HR) to reduce VTEs and increase bleeding as previously published (HR 0.66 and 1.96, Khorana et al., NEJM 2019). Results: Out of 1039 pts, 132 (13%) presented with VTE, 6 (1%) with bleeding. One patients died of VTE and 1 because of bleeding. Patients without any VTE risk factors experience VTE in 20/347 (5%) which translated into a NNT of 55 compared to the NNH of 84 respectively. Before start of chemotherapy 52 (5%) pts (NNT=60) presented with VTE of which 22 were reported symptomatic 21 asymptomatic/incidentally detected VTE on staging scans (9 unknowns). During chemotherapy 79 (8%) pts (NNT=40) were diagnosed with VTE whereas 19 (2%) pts (NNT=162) were diagnosed with VTE after chemotherapy. Conclusions: Our analysis revealed that even mGCT patients without risk factors for VTE show a relevant cumulative VTE incidence of 7%. Especially before and during but not after chemotherapy the benefits of PAK to prevent VTE outweighs the small increased risk of bleeding.
Fracture rates in radium223 (Ra223) treated mCRPC patients (pts): A real-world analysis in 177 pts treated at a single community center 2010-2018.
Authors: Cao Yen Thi Kim Hong , Elias Michael , Trieu Janson , Rojas Vanessa , Anderson Michael J. , Vogelzang Nicholas J.
Published: February 2020

41

Background: Ra223 was FDA approved 5/15/13 as a life extending therapy in conjunction with Standard of Care (SOC) agents for mCRPC in the ALSYMPCA trial. However, agents such as abiraterone (abi) and enzalutamide (enza) were not part of the SOC regimens allowed during conduct of ALSYMPCA. Phase 2 and expanded access programs (EAPs) suggested enhanced activity when abi or enza were given with Ra223. A phase 3 trial (ERA223 Smith et al. Lancet Oncology 2019) comparing Ra223 +/-abi showed an increased fracture (Fx) rate (29% vs 11%) and no survival advantage for the combo, leading to regulatory restrictions on abi and Ra223 combination therapy. However, only 41% of pts in ERA223 received bone health agents (BHAs). This center participated in ALSYMPCA and in the US EAP and based on those data, BHAs were consistently administered monthly during Ra223. The Fx rate in ERA223 did not mirror our clinical experience and thus our institutional Ra223 database was reviewed. Methods: Cohort analysis of pts who received Ra223 for mCRPC under the supervision of NJV. Follow-up was until date of death or last data entry. Results: 177 pts received Ra223 between 11/2010 and 8/2018. Median age 73 at 1st Ra223 (range 40-93); Median PSA (15.8- at 1st Ra223 (range 0.1-1952); Demographics-AA-10, C-130, Asian-9, unspecified- 28; Median Gleason score 8, Median Alk Phos 95 at 1st Ra233 (range 25-1515). Median mos of prior ADT 23 (range 0-247mos). Pts on concurrent abi + pred + Ra223 69 (39%); abi + Ra223 7 (4%); abi + pred prior to Ra223 54 (31%); abi prior to Ra223 4 (2.3%). Enza + Ra223 51 (29%); enza prior to Ra223 39 (22%). 164 pts (93%) were on BHAs before or during Ra223 (denosumab 86 concurrent vs zoledronic acid 64 concurrent). 10 pts (5.6%) had Fxs reported after the start of Ra223 (4 with concurrent abi, 3 with concurrent enza, 3 on Ra 223 w/o concurrent abi or enza; 8/10 Fxs occurred while on BHA’s). Conclusions: In contrast to the ERA223 study where 11-29% of pts experienced Fxs, this real-world experience with Ra223 in which 164/177 pts (93%) received BHAs before or during Ra223 saw a 5.6% Fx rate. When Ra223 was given concurrently with abi or enza and BHAs, the Fx rate was 6/177 (3.4%).
NAD(P)H: Quinone oxidoreductase (NQO1) and catalase expression in nonseminomatous germ cell tumors.
Authors: Hashemi-Sadraei Neda , Adra Nabil , Kessler Kenneth A. , Idrees Muhammad T. , Einhorn Lawrence , Boothman David A.
Published: February 2020

413

Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme which detoxifies quinones and reduces oxidative stress. NQO1 is expressed in multiple tumor types at levels up to 200-fold above normal tissue, including in breast, pancreatic, and non-small cell lung cancers. NQO1 bioactivatable drugs have the potential to deliver tumor-selective DNA damage and cell death by exploiting the elevation of NQO1. Alterations in catalase expression can cause marked cytoprotection. The ratio of NQO1:catalase activities is presumed to be a predictive marker for therapeutic activity of NQO1 bioactivatable drugs. There is no data available on NQO1 and catalase expression in germ cell tumors. Methods: Patients with germ cell tumor who underwent orchiectomy/tumor resection between January 2016 and December 2018 were identified from the Indiana University Melvin and Bren Simon Cancer Center database. Patients with non-seminomatous germ cell tumor of testis or primary mediastinal non-seminomatous germ cell tumor were selected. Immunohistochemistry staining for NQO1 and catalase was performed on tumor tissue. Results: NQO1 and catalase expression were assessed in 16 patients. Fifteen of 16 tumors stained positive for NQO1, 13 of which were moderately to strongly positive. Conversely, the majority of tumors were catalase deficient or only mildly positive for catalase. The details of the Immunostaining is summarized in the table below. Conclusions: Non-seminomatous germ cell tumors appear to have overexpression of NQO1 and deficiency of catalase. NQO1 bioactivatable agents could be beneficial in treating patients with refractory non-seminomatous germ cell tumors.[Table: see text]
Semi-ResMass Study: Residual masses after salvage chemotherapy in men with pure seminoma—A multicenter retrospective analysis.
Authors: Baciarello Giulia , Brard Caroline , Aldea Mihaela , Oing Christoph , De Giorgi Ugo , Morelli Franco , Pouessel Damien , Secondino Simona , Vincenzi Bruno , Tardy Magalie Pascale , Crouzet Laurence , Ladoire Sylvain , Foulon Stéphanie , Fizazi Karim
Published: February 2020

420

Background: Only scarce data exist on the management of residual masses in men who have received two lines of chemotherapy for advanced seminoma. Due to the lack of data, the role of PET scanning, surgery and other additional treatments is controversial in these men. Methods: Data from men with pure seminoma and residual masses after salvage chemotherapy were retrospectively collected from 10 high-volume centers in 3 European countries. We analyzed the clinical management of residual masses (imaging, surgery, pathological data, and additional treatment modalities) and long-term outcomes. Residual mass was defined as a lesion of ≥1 cm after two lines of platin-based chemotherapy. Results: To date, data from 48 patients (pts) with non-progressing residual masses after second line (salvage) chemotherapy have been collected and are included in this analysis. Median age at diagnosis was 36 years (range 31; 42). A post-chemotherapy PET-FDG was performed in 32 (67%) pts. Surgery was performed in 20/48 (41%) pts irrespectively of FDG uptake (no, n=8; yes, n=5). Complete necrosis was found in 16 (80%), viable seminoma in 3 (15%), and teratoma in 1 pt, respectively. All pts with a negative PET (PET-) who underwent surgery (8/8) had complete necrosis. 5/11 pts with a positive PET (PET+) underwent surgery: 3 had a complete necrosis while 2 had viable seminoma. Among those with a PET+, 3 pts (28%) experienced either viable seminoma in residual masses or a subsequent relapse. The absence of FDG uptake correlated with absence of viable cancer (p=0.04). A second relapse occurred in 5/48 pts (10%). Only 2/20 pts who had residual masses resected post 1st salvage chemotherapy subsequently relapsed (one had viable seminoma in the residuals). At a median follow up of 4 years (IC95% [3.5-5.5]), 41/48 pts (87%) were alive. 7/48 patients died of cancer progression. Conclusions: Most men with residual masses after 1st salvage chemotherapy for advanced seminoma may achieve a cure. Pending validation with more pts in this rare situation, PET-FDG may help guide who should be selected for post-chemotherapy resection. Updated results will be presented at the congress.
Clinical presentation and outcomes of patients with testicular tumors in cryptorchid testis.
Authors: Joshi Amit , Simha Vijai , Prabhash Kumar , Noronha Vanita , Menon Santosh , Murthy Vedang , Bakshi Ganesh , Prakash Gagan , Agrawal Archi , Popat Palak , Sable Nilesh , Krishnatry Rahul
Published: February 2020

428

Background: Undescended testis which occurs in 2-4% of all boys confers a natural risk for development of testicular cancer. Cryptorchidism accounts for 10% of all testicular germ cell tumours. The presentation, natural history and outcomes of testicular tumours occurring in cryptorchid testis has not been described in literature so far. Methods: Case records of patients enlisted in the prospectively maintained ‘ testicular cancer database’ at our tertiary cancer care hospital were retrospectively reviewed. Any patient who presented with testicular germ cell tumour with the testis being absent in the scrotum was considered as ‘undescended testis’. Results: From our database of 490 patients with testicular tumours presenting from the year 2014 -2018, 42 patients had testicular cancer in cryptorchid testis. The mean age was 32.9 years (Range:17-56). 24(57.14%) had seminoma and 18(42.86%) had non seminomatous tumors. Orchidopexy was done in 22(52.3%) patients at median age of 30 yrs (Range 2-33). 23 patients had prior undescended testis underwent high inguinal orchidectomy, 13 patients had testis located in pelvis and 6 patient had testis located in the upper abdomen. The average maximum size of tumours presenting with after orchidopexy was 7.34cm (4-10.5cm), in those presenting with pelvic tumours was 9.86cm (7-12.6cm) and in those with intraabdominal tumours was 14.3cm (9-20cm). The median follow-up for these patients was 36 months (3-64 months). There were 6 patients who relapsed after front line therapy whom 3 were salvaged with second line chemotherapy and 2 patients had residual disease at their last follow up. There was one death due to disseminated tumour with brain metastasis. The disease free survival for the whole cohort was 92.85%. Conclusions: The tumours developing in intraabdominal location of testis presented with a larger size and orchiopexy apart from its role in prevention of testicular cancer also helps in surveillance and early detection leading to effective treatment of these highly curable cancers. In the first of its series on testicular tumours in the cryptorchid, we show that they are also as curable as the germ cell tumours developing in the descended testis.
Survival outcomes associated with different palliative systemic therapies (PSTs) in patients with metastatic bladder cancer (mBC).
Authors: Vafaei-Nodeh Saba , Beigi Arshia , Huang Longlong , Mimmack Gillian , Sun Shaun Zheng , Ko Jenny J.
Published: February 2020

450

Background: Cisplatin-based (Cis) chemotherapy (C) is considered standard first-line regimen for treating mBC. In individuals medically unfit for Cis, carboplatin-based (Cb) regimens may be considered. Alternative PSTs include immunotherapy (I) as first or second-line treatments. The purpose of this study is to investigate current trends and clinical outcomes of PSTs in patients with mBC. Methods: A retrospective analysis was conducted on patients initially diagnosed with bladder cancer from Sep 2014 to Dec 2016 and had de novo or recurrent mBC. Kaplan-Meier method and Log-Rank test were used to compare survival outcomes among patients receiving different PSTs. Results: In 273 patients, 123 (45.1%) had de novo and 150 (54.9%) had recurrent disease. The median overall survivals (mOS) were 5.3 (95% CI: 3.7-8.2) and 6.5 months (95% CI 5.1-8.9), respectively (p=0.54). Patients received one of the following: C (23.1%), I (6.2%), C followed by I (C/I, 10.6%), and no treatment (NT, 60.1%). The mOS were 9.5 (95% CI: 7.1-12.5), 9.2 (95% CI: 6.1 - not estimable (NE)), 23.9 (95% CI: 16.30-NE), and 3.5 months (95% CI: 3.03-4.30), respectively. Each treatment group had a longer mOS than the NT group (p<0.01 in all three pairwise comparisons). Additionally, patients receiving C/I had a longer mOS than those receiving either C or I (p<0.001 and p=0.0497, respectively). The mOS were not statistically different between C vs I (p=0.2649). In patients receiving any C, 50.0% received Gemcitabine (G) plus Cis and 30.4% received G plus Cb. The mOS were 11.0 (95% CI: 8.7-19.7) and 14.4 months (95% CI:10.7-19.2), respectively, which were not significantly different (p=0.36). Conclusions: Despite the general preference for G plus Cis over Cb, this study showed that G plus Cb as a PST may be a comparable and efficacious treatment. While C currently remains the preferred initial line of PST, patients receiving I had similar survival outcomes to the C group despite many of the patients having Cis ineligibility. Real-world mOS of 2 years in patients who receive both C and I is unprecedented and indicates efficacy of PST. This study provides further evidence for immunotherapy as first or second-line regimen in treating mBC.
Proposal of a new subcategory of the pT3 classification: Effects of tumor location and subclassification of renal pelvic pT3 to predict the prognosis of pelvic carcinoma more accurately than the current TNM classification.
Authors: Sano Tomoyasu , Hattori Ryohei , Yamada Shin , Kamihira Osamu , Kobayashi Hiroaki , Tsuji Yoshikazu , Sassa Naoto , Gotoh Momokazu , Tsuzuki Toyonori
Published: February 2020

455

Background: Whether pT3 urothelial carcinoma of the renal pelvis (UCRP) and urothelial carcinoma of the ureter (UCU) show the same prognosis or not remains controversial.This study aims to reveal whether the prognosis of pT3 UCRP shows similar to those of pT3 UCU. Methods: We retrospectively evaluated 954 patients who underwent nephroureterectomy between 1983 and 2017 at our institutions.None of the patients received neoadjuvant therapy.All HE slides for each patient were reviewed by a single genitourinary pathologist (TT).pT3 UCRP was subdivided pT3a (urothelial carcinomas that extend only to the renal medulla) and pT3b (urothelial carcinomas that extend to the renal cortex and/or peripelvic adipose tissue) according to the criteria previously we proposed.Fine and Gray model was developed to predict the reccurence-free survival (RFS) and cancer-specific survival (CSS). Results: Overall, 954 patients were eligible for this study, 493 of whom were pT3 with only renal pelvis and 461 of whom were pT3 with only ureter. A total of 202 cases were pT3 UCRP and 146 were pT3 UCU. The pT3 subclassification of UCRP resulted in 79 pT3a and 120 pT3b cases.No significant difference was found in the 5-yr RFS and 5-yr CSS between pT3a UCRP and pT2 UCRP and pT2 UCU. (RFS; pT3a UCRP vs pT2 UCRP: HR = 1.19 p = 0.74; pT3a UCRP vs pT2 UCU HR = 0.88, p = 0.72, CSS;pT3a UCRP vs. pT2 UCRP: HR = 0.69; p = 0.56; pT3a UCRP vs. pT2 UCU: HR = 0.66, p = 0.31) The RFS rate was significantly higher in the pT3a UCRP than that of pT3b, (pT3a vs pT3b: HR = 2.59, p = 0.0038) and so was the CSS rate. (pT3a vs. pT3b: HR = 3.1 p = 0.001) In fine and gray model analysis for RFS, pT stage, lymph node metastasis, WHO/ISUP grade, lymphovascular invasion were independently associated with tumor recurrence, whereas pT stage, lymph node metastasis, operation method, histologic type, lymphovascular invasion, gross type, adjuvant chemotherapy were independently associated with cancer mortality. Conclusions: Subclassifying pT3 UCRP into pT3a and pT3b was useful in determining the prognosis of different patients.The pT3b UCRP showed similar outcome compared to those of UCU.
Micropapillary urothelial carcinoma (mpUC): A comparative analysis of oncologic outcomes compared to conventional urothelial carcinoma (CUC).
Authors: Diamantopoulos Leonidas Nikolaos , Khaki Ali Raza , Gadzinski Adam John , Winters Brian , Vakar-Lopez Funda , Tretiakova Maria S. , Gore John L. , Schade George R. , Psutka Sarah P. , Hsieh Andrew Caleb , Lee John Kyung , Yezefski Todd , Schweizer Michael Thomas , Cheng Heather H. , Yu Evan Y. , Lin Daniel W. , Montgomery Robert B. , Grivas Petros , Wright Jonathan L.
Published: February 2020

459

Background: MpUC is a rare variant associated with adverse outcomes. We describe our institutional experience and compare clinicopathologic features and survival between patients with mpUC and CUC. Methods: Patients with mpUC or CUC at radical cystectomy (RC) or transurethral resection of bladder tumor were identified from a retrospective institutional RC database. Clinicopathologic/treatment data were extracted and compared using T-test and χ2 test. Recurrence free survival (RFS) and overall survival (OS) from RC to first recurrence or death were estimated using the KM method. Factors identified as significant in univariable (UVA) Cox regression analysis for OS were included in multivariable analysis (MVA). Results: 64 consecutive patients with mpUC and 457 with CUC were identified (2003 - 2018); 36 (56%) and 188 (41%) received neoadjuvant chemotherapy (NAC). MpUC had higher incidence of pT3/4 (41% vs. 28%) or pN+ disease (39% vs. 17%), carcinoma in-situ (52% vs. 24%) and lymphovascular invasion (LVI, 39% vs. 16%) at RC, compared to CUC (all p < 0.05). Rates of ypT0N0 after NAC were comparable between groups (25% vs. 35%, p = 0.26). Median follow-up was 62 months (95% CI 55.4 – 68.3). 5-year RFS was 24% (mpUC) vs. 58% (CUC), p = 0.001. 5-year OS was 40% (mpUC) vs. 69% (CUC), p = 0.001. MpUC histology was not independently associated with OS after adjusting for pT stage, node ratio (# nodes +/ # nodes removed) and ECOG status (Table). Conclusions: Patients with mpUC presented with advanced stage at RC, while they showed inferior RFS and OS, when compared to CUC. However, rates of pathologic response to NAC were comparable to CUC and mpUC was not associated with OS in MVA. Further studies are needed to define the optimal management of this variant. [Table: see text]
Outcomes of urothelial carcinoma patients with central nervous system metastases.
Authors: Andrews Erik , Curran Catherine , Grivas Petros , Diamantopoulos Leonidas Nikolaos , Kanesvaran Ravindran , Wang Jue , Jain Rohit K. , Tandon Ankita , Drakaki Alexandra , Sonpavde Guru
Published: February 2020

468

Background: Urothelial carcinoma (UC) metastatic to the central nervous system (CNS) is extremely rare. Given the lack of systematic data regarding outcomes in UC metastatic to the CNS, we conducted a retrospective multicenter study to more broadly characterize outcomes. Methods: Patients (pts) diagnosed with metastatic UC to the CNS were identified from collaborating institutions. Data were collected for demographics, clinical and pathological variables. Descriptive statistics were reported to examine tumor regression, time to treatment discontinuation or failure (TTF), and overall survival (OS). Results: 39 pts with UC metastatic to the CNS were evaluable from 6 institutions. The ECOG-PS ranged from 0-4 (median 2), the median age was 67 (range 39-82), and 8 (20.5%) were female. The histology consisted of pure urothelial, mixed predominant urothelial, and mixed predominant non-urothelial in 26 (66.7%), 8 (20.5%), and 5 (12.8%) pts, respectively. The sites of CNS metastases (mets) were the brain, meninges, and a combination of CNS sites in 37 (95%), 1 (2.5%) and 1 (2.5%) pts, respectively. 33 (84.6%) pts received radiation therapy (RT) to their mets and 6 (15.4%) did not. Of 16 pts who received systemic therapy (ST), cisplatin-based chemotherapy, non-cisplatin based chemotherapy, and PD-1/L1 inhibitors were administered in 6 (37.5%), 5 (31.25%), and 5 (31.25%) pts, respectively. The overall median TTF and OS were 90 and 154 days (d). The median OS for pts who had ST compared to those who did not was 193.5 (n=12) versus 71 (n=17) d. The median OS for pts who had RT compared to those who did not was 92 (n=25) versus 15.5 (n=4) d. The median OS for pts who received neither ST nor RT, compared to pts receiving both, was 12 (range 7-19) versus 232 (n=11) d. Best response to systemic therapy PR, CR, SD and PD were seen in 2 (12.5%), 1 (6.25%), 1 (6.25%) and 12 (75%) pts, respectively. For the 5 pts who received RT only, best response PR and PD were seen in 2 (40%) and 3 (60%) pts, respectively. Conclusions: Pts with UC metastatic to the CNS present with a poor performance status and have outcomes that are dismal and appear worse than those with metastases to other organs. A combination of systemic and radiation therapy might achieve improved outcomes in selected pts.
Efficacy of neoadjuvant chemotherapy followed by resection in primary and secondary muscle-invasive bladder cancer (MIBC).
Authors: An Josiah , Sanchez Kevin , Mott Sarah L. , Garje Rohan
Published: February 2020

497

Background: Neoadjuvant chemotherapy followed by cystectomy in MIBC is associated with improved survival compared to cystectomy alone. Recent retrospective studies indicated that secondary MIBC (non-MIBC progressed to MIBC) had worse outcome with cisplatin based neoadjuvant chemotherapy when compared to primary MIBC. To further evaluate this observation, we queried our database to assess the differential response and determine if prior use of intravesical therapy diminishes the effect of cisplatin based neoadjuvant chemotherapy. Methods: A total of 387 patients diagnosed with T2-4 or N0-3 and M0 from 2000-2018 and underwent cystectomy were retrospectively chart reviewed for demographics, treatment and outcomes at University of Iowa Holden Comprehensive Cancer Center. Cox regression models were utilized to assess differences in recurrence-free survival (RFS) and overall survival (OS). Time was calculated from cystectomy to recurrence or death due to any cause for RFS and OS, respectively. Results: Of the 387 patients, 324 patients had primary MIBC and 63 had secondary MIBC. Median follow up was 25.8 months. Intravesical therapy was administered to 98% (62/63) of secondary MIBC patients. Neoadjuvant chemotherapy was administered to 38% (122/324) of primary MIBC patients and 21% (13/63) of secondary MIBC patients. NAC had no difference in response rates (CR and PR) for primary vs secondary MIBC (p=0.73). Additionally, there was no difference between the primary and secondary MIBC with regards to RFS (p=0.54) and OS (p=0.12) on univariate analysis. The effect of neoadjuvant chemotherapy did not differ based on prior use of intravesical therapy in terms of RFS (p=0.61) or OS (p=0.40). Additionally, neoadjuvant chemotherapy irrespective of prior use of intravesical therapy was not associated with RFS (p=0.66) or OS (p=0.15). Conclusions: Prior intravesical therapy was not associated with differential efficacy of neoadjuvant chemotherapy in secondary MIBC when compared to primary MIBC.
Association of an immune gene signature with pathologic response and outcome after neoadjuvant pembrolizumab (pembro), compared to neoadjuvant chemotherapy (NAC), in muscle-invasive bladder cancer (MIBC).
Authors: Necchi Andrea , Raggi Daniele , Briganti Alberto , Farè Elena , Giannatempo Patrizia , Marandino Laura , Bianchi Marco , Gallina Andrea , Salonia Andrea , Gandaglia Giorgio , Fossati Nicola , Capitanio Umberto , Montorsi Francesco , Boormans Joost L. , Liu Yang , de Jong Joep , Black Peter C. , Dittamore Ryan , Davicioni Elai , Gibb Ewan
Published: February 2020

533

Background: In the PURE01 study (NCT02736266), neoadjuvant pembro resulted in 42% pathologic complete responses (pT0) in patients (pts) with MIBC. In this study, we investigated immune transcriptome signatures and molecular subtyping as potential predictors of pembro efficacy. Methods: Pts enrolled in the PURE01, which is still recruiting pts in its amended design, had predominant urothelial carcinoma histology and stage cT≤4N0 MIBC. Biomarker analyses included transcriptome profiling for 78 pts. A cisplatin-based NAC cohort of 140 cT≤4N0 MIBC pts was used for comparison. The association of Immune190, immune hallmark RNA signatures and molecular subtypes (TCGA, Consensus classifier, Genomic subtyping classifier [GSC]) was evaluated with respect to pT0 and recurrence-free survival (RFS). Multivariable logistic regression analyses (MVA) were used adjusting for the clinical T-stage and gender. Results: The Immune190 signature was significant for pT0 on MVA (OR: 1.54, 95%CI: 1.1-2.3, p=0.02) in the PURE01 cohort, but not in NAC cohort (OR: 0.96, 95%CI: 0.8-1.2, p=0.73). The hallmarks for IFN-γ (OR: 1.10, 95%CI: 1-1.2, p=0.007) and IFN-α response (OR: 1.07, 95%CI: 1-1.1, p=0.009) were also associated with pT0 for PURE01, but not for NAC (IFN-γ: OR: 0.99, 95%CI: 0.9-1.1, p=0.846 and INF-α: OR: 0.99, 95%CI: 0.95-1.04, p=0.806). In PURE-01, patients with Immune190 scores >0.35 had 100% 2-y RFS vs 80% of those with ≤0.35; no difference was observed in NAC pts, as well as for the other hallmarks in both groups. The neuroendocrine (NE)-like subtype had the worst 2-y RFS in all three subtyping models (33%, p<0.01) whereas the GSC Claudin-low subtype had the best outcome with no recurrences within 24 months. The other subtypes had RFS ranging from 75-86% in TCGA, 53-89% in Consensus, and 74-92% in the GSC. Conclusions: We found RNA Immune190 signature was reliably associated with response and outcome after neoadjuvant pembro. Molecular subtyping revealed special subtypes with outlier outcomes. These data suggest RNA profiling may provide a potential tool for personalizing the neoadjuvant therapy approach. Clinical trial information: NCT02736266.
BCG shortage: Reassessing the clinical viability of Bacillus Calmette-Guerin (BCG) after reconstitution.
Authors: Brooks Nathan , Nagaraju Supriya , Matulay Justin T. , Han Xiang-Yang , Kamat Ashish M.
Published: February 2020

534

Background: To address the current worldwide shortage of BCG, the AUA and SUO recommend reducing the dose to 1/3rd vial and enabling 3 patients to be treated in one setting. The manufacturer states that BCG must be used immediately after reconstitution, despite literature in the bacteriological world suggesting that M. Bovis might be viable for longer than a few hours. Herein we sought to study the viability of BCG after re-constitution at time points relevant to clinical practice. Methods: TICE BCG from separate lots was reconstituted per the manufacturer’s guidance and stored at 4 °C without light exposure. At predetermined time points, BCG was inoculated on Selective Middlebrook 7H11 agar in triplicate and incubated at 37°C with 5% CO2. M. smegmatis served as a positive control and un-inoculated media was incubated for 2 weeks as a negative control. CFUs were assessed between 3 and 4 weeks from plating. Acid-fast staining confirmed the presence of BCG. Data was analyzed as the mean of replicated experiments and compared to the reference (Time 0) using Student’s T-tests. Results: No significant difference in CFUs was observed for BCG between 0 and 8 hours after reconstitution (Table). Colony forming units significantly declined starting 24 hours after reconstitution, though the magnitude of this difference was less than 10 fold (which falls within the range of CFUs listed for the vial by manufacturer). Viability remained constant for both lots analyzed. Conclusions: Given the recurrent shortages of BCG, split dosing may become a clinical necessity. This often presents logistic quandaries since the manufacturer recommends each vial must be used within 2 hours. We have shown that the viability of TICE BCG is unaltered at least 8 hours after reconstitution and only begins to decline at 24 hours after reconstitution. This should allow pharmacists and physicians administering BCG more leeway in scheduling patients for split dose therapy. [Table: see text]