bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Wnt signaling pathway (WSP) aberrations in advanced prostate cancer.
Authors: Ghali Fady , Patel Devin , Jamieson Christina , Parsons J Kellogg , McKay Rana R.
Published: February 2020

203

Background: Aberrations in Wnt signaling pathway (WSP) are implicated in disease progression and resistance of multiple malignancies including prostate cancer (PCa). We sought to characterize the clinical phenotype and molecular genotype of PCa patients with WSP alterations. Methods: Eligible patients included those with PCa having undergone clinical-grade next generation DNA sequencing of tumor derived from prostate or metastasis tissue. We identified patients with somatic activating mutations in CTNNB1 and RSPO2, or inactivating mutations in APC, RNF43, or ZNRF3. Patient and disease characteristics were collected. Clinical and outcome parameters were associated with WSP mutation status using STATA(V. 13.1, College Station, Texas). Results: A total of 169 patients were identified of whom 29 (18.1%) had a WSP activating mutation. Median age of the overall cohort was 64.85 (IQR 56.77, 70.36). 115 (68.0%) patients had Gleason 8-10 disease, 34 (20.1%) presented with de novo metastatic disease, 85 (50.3%) developed CRPC and 23 (13.6%) developed visceral metastases. Clinical characteristics were similar between biomarker groups. There was no association with the presence of a Wnt activating mutation and RB1, p53, pTEN, or BRCA1/2 alteration. Median time to CRPC was 39.42 (IQR 14.50 – 87.52) and 24.39 (IQR 14.99 – 46.03) months for no-WSP and WSP-aberrant respectively. Median 5-year OS was 83.7% (95% CI 73.0-90.4%) and 79.6% (95% CI 52.9 – 92.2%) months for no-WSP and WSP-aberrant respectively. Table evaluates biomarker status with time to CRPC development and overall survival (OS). Conclusions: We observe that somatic WSP activating mutations are present in 18.1% of patients with mPCa, consist with prior reports. Understanding the clinical significance of WSP alterations is critical to inform treatment strategies in patients with advanced disease.[Table: see text]
The psychological impact of early prostate cancer: A prospective evaluation.
Authors: Dresler Hadas , Keizman Daniel , Sarid David , Oren Debi
Published: February 2020

210

Background: Early prostate cancer is often considered as being associated with a good prognosis and quality of life. However, early prostate cancer research mainly focus on its medical aspects, rarely considering its psychological impact. We aimed to prospectively analyze the correlation between illness perception, quality of life (QOL) and psychological distress among prostate cancer patients, in comparison to healthy controls. Methods: Early prostate cancer patients and healthy controls were prospectively recruited through convenience sampling. Participants filled questionnaires of demographic, illness perception (IPQ-R), QOL (MOS SF-36) and anxiety and depression (HADS). We compared the illness perception, QOL and psychological distress between patients and healthy controls. Results: 51 early prostate cancer patients and 65 healthy men controls were included. Median age was 69. Patients and healthy participants differed in illness perception ['consequences' (p<.001), 'emotional representations' (p<.001)] and psychological distress (p<.01). There was a correlation between the patient illness perception and QOL (p<.05) and psychological distress (p<.05). Among patients, the correlation between psychological distress and QOL was mediated by illness perception (p<.05), while it was not among controls. Conclusions: Diagnosis of early prostate cancer may have a psychological impact. Among early prostate cancer patients, a correlation may exist between illness perception, and quality of life (QOL) and psychological distress. Our results emphasize the need to identify patient distress and to implement therapeutic interventions also in a disease which usually is associated with a good prognosis.
Cost-effectiveness of upfront therapeutic options in low-volume de novo metastatic hormone-sensitive prostate cancer.
Authors: Parikh Neil Rohit , Chang Eric M. , Nickols Nicholas George , Rettig Matthew , Raldow Ann C. , Steinberg Michael L. , Koontz Bridget F. , Vapiwala Neha , Deville Curtiland , Feng Felix Y , Spratt Daniel Eidelberg , Reiter Robert Evan , Phillips Ryan , Tran Phuoc T. , Kishan Amar Upadhyaya
Published: February 2020

211

Background: Low-volume de novo metastatic hormone-sensitive prostate cancer (mHSPC) has historically been treated with lifelong androgen deprivation therapy (ADT). Recently, however, the addition of several advanced therapeutic options – radiation therapy (RT) to the primary, advanced hormonal therapy agents such as abiraterone acetate/prednisone (AAP), and chemotherapy – to ADT have been shown to improve survival in low-volume mHSPC. The objective of this study was to compare the cost-effectiveness of treating low-volume mHSPC patients upfront with RT+ADT, AAP+ADT, or docetaxel+ADT. Methods: A Markov-based cost-effectiveness analysis was constructed comparing three treatment strategies for low-volume mHSPC patients: (1) upfront RT+ADT --> salvage AAP+ADT --> salvage docetaxel+ADT; (2) upfront AAP+ADT --> salvage docetaxel+ADT, and (3) upfront docetaxel+ADT --> salvage AAP+ADT. Transition probabilities were calculated using data from STAMPEDE arms C/G/H, COU-AA-301, COU-AA-302, and TAX-327. RT was delivered via five-fraction stereotactic body radiation therapy. The analysis utilized a 10-year time horizon, and a $100,000/quality adjusted life year (QALY) willingness-to-pay threshold. Utilities were extracted from the literature; costs were taken from Medicare fee schedules and VA oral drug contracts. Results: At 10 years, total cost was $140K, $259K, and $189K, with total QALYs of 4.66, 5.03, and 3.72 for strategies (1) upfront RT+ADT, (2) upfront AAP+ADT, and (3) upfront docetaxel+ADT, respectively. Compared to upfront RT+ADT, upfront AAP+ADT was not cost-effective (ICER: $321K/QALY). This result remained unchanged even after modification of various model inputs in 1-way sensitivity analysis. Upfront docetaxel+ADT was both more costly and less effective than upfront RT+ADT (ICER: -$53K/QALY). Conclusions: At 10 years, RT+ADT is cost-effective compared to other advanced systemic therapy options alone, and should be considered as a viable treatment strategy in all patients with a low-burden of metastatic disease. Additional studies are needed to determine whether any benefit exists in combining RT to the primary with upfront advanced systemic therapy.
The effect of androgen deprivation therapy on 68GA-PSMA-tracer uptake in nonmetastatic prostate cancer patients.
Authors: Cem Onal , Guler Ozan Cem , Torun Nese , Reyhan Mehmet , Yapar Ali Fuat
Published: February 2020

22

Background: To evaluate the effect of neoadjuvant androgen deprivation treatment (ADT) on prostate specific membrane antigen (PSMA) tracer uptake demonstrated in 68Ga-PSMA-positron emission tomography (PET/CT) in non-metastatic hormone-naïve prostate cancer patients. Methods: The clinical data of 108 prostate cancer patients who received neoadjuvant ADT were retrospectively analyzed. All patients had a baseline 68Ga-PSMA-PET/CT scan and a second scan was delivered median of 2.9 months after initiation of ADT. Patients with clinical and radiological evidence of distant metastasis were excluded from the study. The maximum standardized uptake value (SUVmax) of primary tumor (SUVp) and metastatic lymph nodes (SUVln) as well as PSA response were assessed between pre- and post-ADT 68Ga-PSMA-PET/CT scans. Results: The median SUVp and SUVln were 14.0 (range, 4.9 – 78.4) and 13.2 (range, 3.6 – 64.5), respectively. There was a significant moderate correlation between baseline serum PSA and SUVp (Spearman = 0.513, p<0.001). There were significant decreases in post-treatment serum PSA, SUVp, and SUVp. A decrease in SUVp was seen in 91 patients (84%) with a median value of 66% (range, 5% – 100%), while 17 patients (16%) had no change in or an increase in PSMA tracer uptake with a median value of 24% (range, 0% – 198%). Patients with Gleason score (GS) of 7 had significantly higher metabolic response rates compared to other patients. The disease progression was significantly higher only in patients with GS > 7 disease compared to GS 7 disease. The PSA response to ADT was lowest in patients with ISUP high-grade tumors. A total of 16 patients (15%) had progressive disease, and in 9 patients (8%), radiotherapy decisions were modified according to post-treatment 68Ga-PSMA-PET/CT scans. Conclusions: The current study includes the largest number of patients analyzed to date and demonstrates that ADT causes a significant decrease in serum PSA values and SUVp and SUVln. The authors demonstrate that 68Ga-PSMA-PET/CT may be used as a quantitative imaging modality after neoadjuvant ADT in hormone-naïve non-metastatic PC patients.
Comparative efficacy of local versus systemic salvage therapies for recurrent prostate cancer after primary radiotherapy.
Authors: Bauman Glenn , Ding Keyue , Chin Joseph , Iaboni Alessandra , Klotz Laurence , Dearnaley David P. , Horwitz Eric M. , Crook Juanita M. , O'Callaghan Christopher J.
Published: February 2020

221

Background: We sought to compare two common salvage strategies for radio-recurrent prostate cancer: androgen deprivation therapy (ADT: PR7 RCT NCT00003653) or local salvage ablation using cryotherapy (CRYO: single institution study Williams, Eur Urol. 2011;60(3):405). Methods: Pre-salvage therapy prognostic variables common to the two datasets (Gleason score at initial treatment, time from original RT, use of ADT at time of original RT, PSA at time of salvage, patient age) were used for propensity matching between patients from previously published ADT (1) and CRYO (2) datasets. Progression free survival (PFS, defined as time from initial treatment to development of castrate resistance or death); Disease Specific Survival (DSS, defined as time from salvage to prostate cancer related death) and Overall Survival (OS, defined as time from salvage to death from any cause) were compared between the propensity matched cohorts using Log-Rank and Cox PH regression statistics. Raw linear propensity scores included in the PH model to account for residual variability. A planned subset analysis examined the effect of neoadjuvant ADT among the CRYO cohort (no CRYO patients had adjuvant ADT). Results: Overall, 1119/1386 (ADT) and 172/187 (CRYO) patients were included in the propensity matched analysis. Median follow up was 6.7 yrs (ADT) and 18.7 yrs (CRYO). Median PFS (95% CI) was 10.7 yrs (9.5, 12.3) for CRYO vs. 7.0 yrs (6.1, 10.0) for ADT (HR 0.63 (0.44, 0.89), p = 0.009). Median OS was also longer for CRYO vs. ADT: 12.3 (11.0, 13.8) vs. 10.2 (9.4, not reached) yrs (HR 0.69; p = 0.02). 10 year DSS event rate was 16.5% CRYO vs. 18.5% ADT but was not statistically different. Neoadjuvant ADT did not affect outcomes in CRYO. Conclusions: A 3-year PFS and 2-year OS benefit was noted for the CRYO vs. ADT cohorts while no difference was noted in DSS. Potential explanations include residual bias not corrected for in the propensity scoring, variable follow-up duration, adverse effects from differing cumulative exposure to ADT or a combination of these factors. Prospective comparisons are required to control for these potential biases and compare other important outcomes such as side effects and quality of life.
Extension of bone marrow involvement and cytopenias in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Preto Daniel D Almeida , Soares Marcella de Oliveira Gonçalves Prince , Alves Wilson Eduardo Furlan Matos , de Lima Marcos Alves , Neif Joao Antonio Junior , Zucca Luis Eduardo Rosa , Carcano Flavio Mavignier
Published: February 2020

222

Background: Most of bone metastatic castration-resistant prostate cancer (mCRPC) patients present variable extension of bone marrow involvement which in some cases may influence hematopoiesis. Cytopenias may hinder clinical practice, especially in decision making, regarding the use of myelotoxic drugs. The aim of this study was to assess whether the extension of bone marrow involvement in mCRPC patients is a prognostic factor for developing cytopenias. Methods: We retrospectively reviewed 1649 hemograms from 103 bone mCRPC cases. Patients were pooled in two groups, according to the extension of bone metastasis assessed by skeletal scintigraphy: ≤10 lesions (group A) and >10 lesions or superscan (group B). Time for cytopenia event (event-free survival) and overall survival (time from first cytopenia event until death) were calculated using the Kaplan-Meier method and differences between survivals were tested using the log-rank test. Univariable analysis were performed to determine any significant prognostic factor. Results: The median event-free survival (EFS) was longer in patients with ≤10 bone lesions (group A) on the margin of significance (41.9 vs 23.6 months; p=0.051). The exploratory analyses for severe cytopenia events (grade 3-4) also showed a longer EFS for group A (51.8 vs 31.7 months; p=0.050). When group B was stratified into two subgroups (11-20 bone lesions vs >20 or superscan), there was no significant difference in EFS (19.1 vs 24.2 months; p=0.14). The median overall survival (OS) was 3.3 (1.9-4.6) months, regardless the extension of bone involvement. Patients in the group with more bone lesions showed higher mean PSA levels (55.5 vs 40.3 ng/mL; p=0.01). ECOG, stage disease, Gleason score, visceral metastases, types of cytopenia event (anemia, neutropenia or thrombocytopenia), number of chemotherapy lines, and antialgic radiotherapy did not show difference between groups. Conclusions: The extension of bone metastasis in mCRPC seems to be a prognostic factor for developing cytopenias, but is not related to OS. Additional analyzes with a larger sample are needed to assess whether any clinical variables may be associated with cytopenia event.
Real-world utilization of radium-223 (Ra-223) for the treatment of metastatic castration-resistant prostate cancer (mCRPC): A U.S. tertiary oncology center analysis.
Authors: McKay Rana R. , Silver Rebecca , Bhak Rachel , Korves Caroline , Cheng Mu , Appukkuttan Sreevalsa , Simmons Stacey J. , Duh Mei Sheng , Taplin Mary-Ellen
Published: February 2020

223

Background: Guidelines for optimal sequencing of approved mCRPC therapies do not exist. This study evaluated treatment patterns and overall survival (OS) among patients (pts) with mCRPC treated with Ra-223 in an academic clinical setting. Methods: A retrospective chart review study was conducted at Dana-Farber Cancer Institute of bone metastases-predominant mCRPC pts treated with Ra-223. Treatment patterns from 2013-2018 were evaluated including Ra-223 initiation pre- vs. post-chemotherapy (chemo). OS was examined using Kaplan-Meier medians and 95% confidence intervals (CIs). Results: 220 pts were treated with Ra-223 (64 pre-chemo, 83 post-chemo, 73 no chemo). Median Ra-223 injections per pt was 6.0 and 5.0 in the pre- vs. post-chemo cohorts, respectively (p<0.001). Mean chemo cycles received was 9.0 (pre-chemo) and 9.2 (post-chemo); on average, Ra-223 was given in the 3rd and 5th mCRPC line of therapy (pre- and post-chemo, p<0.001). 41.8% of pts were treated with Ra-223 in combination (combo) with another mCRPC therapy, commonly abiraterone acetate (37.0%) or enzalutamide (44.4%). The majority received combo therapy for the duration of Ra-223 treatment. 17.6% started another agent after Ra-223 initiation; 17.6% initiated Ra-223 while on an established therapy. Median OS from Ra-223 initiation was 12.4 months (95% CI 10.2, 13.9). Median OS from first mCRPC treatment was slightly longer for pts with Ra-223 pre- vs. post-chemo (by 2 months) and for pts with Ra-223 combo vs. monotherapy (by 3 months). Conclusions: Ra-223 improves OS in mCRPC, and longest OS was seen in those with Ra-223 pre-chemo. Retrospective analysis of 5 years of Ra-223 treatment data from an academic center demonstrates that pts treated pre-chemo on average obtained 1 additional cycle of Ra-223, subsequent chemo administration was not limited and OS measured from first mCRPC therapy was not significantly different.[Table: see text]
FDG and PSMA PET in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Zukotynski Katherine A. , Jadvar Hossein , Cho Steve Y. , Kim Chun Ki , Cline Kathryn , Emmenegger Urban , Hotte Sebastien J. , Pond Gregory Russell , Winquist Eric
Published: February 2020

23

Background: We hypothesized 18F-DCFPyL (PSMA-based tracer) and/ or 18F-FDG (glucose metabolism-based tracer) PET/CT might provide different/complementary molecular imaging information in men with mCRPC treated with abiraterone (A) or enzalutamide (E). Methods: In this prospective cohort study (MISTER trial) mCRPC patients (pts) had conventional imaging and both PSMA and FDG PET/CT prior to standard treatment with A or E, repeated after ~10 weeks on treatment. The main objective was to compare changes in PET/CT findings with conventional imaging. Median of PET maximum standardized uptake value (SUVmax) was measured across all PET avid disease sites and change in SUVmax was evaluated in the 5 hottest sites per patient. Review of PET/CT was performed by 3 experts based on consensus. Results: 36 men were enrolled between 2/2017-12/2018, of whom 28 had treatment and followup imaging. To date, 13 cases have been reviewed: mean age 71.2 years, 7 (53.9%) were ECOG=0, median duration since diagnosis of initial cancer 7.5 months and 8 (61.5%) were stage II/III. PSMA detected more skeletal metastases, positive nodes and non-skeletal, non-nodal metastases in 5/5/3 (39%/39%/23%) men, while FDG detected more non-skeletal, non-nodal metastases in 1 man. Following treatment, new lesions were seen in 3 men on both PSMA and FDG, 3 with PSMA only, and 1 with FDG only. 12 men had baseline FDG-avid disease with median SUVmax 6.5 pre-treatment and 3.8 following therapy (all men had lower SUVmax post-treatment). All 13 men had PSMA-avid disease with median SUVmax 17.6 at baseline and 18.7 post-therapy. Following treatment, 8/12 men (67%) had SUV declines ≥30% (2 had new lesions), 4 had declines of 0-30% (2 had new lesions) using FDG; at followup, 1/13 men had PSMA SUVmax declines ≥30% or more, 6 had declines of 0-30% (2 had new lesions), 5 had SUV increases of 0-30% (4 had new lesions) and 1 had >30% increase. Conclusions: In early analyses, PSMA identified more disease burden in mCRPC pts and was more avid than FDG. SUVmax for FDG declined following treatment in all men, while PSMA changes were heterogeneous. Potential prognostic value of early PSMA and FDG imaging changes on clinical outcomes will be correlated with conventional imaging along with review of remaining cases. Clinical trial information: NCT02813226.
The impact of race and insurance status on survival of prostate cancer patients.
Authors: Matthews Hew Trevanne Rose , Hew Jason Desmond , Chhatrala Hardik Satish , Tfirn Ian , Kadakia Meet , Gautam Shiva , Pham Dat C.
Published: February 2020

233

Background: While prostate cancer mortality has declined in the in the general population, it remains high in African Americans. The aim of our study is to determine whether race and insurance type affect treatment outcomes in prostate cancer patients at our institution. Methods: A retrospective chart analysis between 2012 and 2017 of 2763 prostate cancer patients was done at our institution. We collected data on age, race, stage, insurance, treatment history, date of diagnosis, Gleason score, date of death. The healthcare insurance information was categorized into Medicare with and without supplement, VA, Medicaid, no insurance/self- pay, City Contract and private. City Contract is the city sponsored health care access for person with low income living in the Duval County. Univariate and multivariate chi square analysis with odd ratio was performed, 95 % confident intervals were evaluated with P value < 0.05. Results: African Americans were 2.93 times more likely to experience death than Caucasians (Odds Ratio, OR, 1.79-4.78, 95 % CI). Both Private and VA insurance were more likely to have a lower stage of prostate cancer compared to City Contract (0.53 times, 0.30-0.93, and 0.411 times, OR 0.23-0.84 95 % CI respectively). African Americans were significantly more likely to have a more advanced cancer stage when compared to Caucasians (1.85 times, 1.49 -2.29 95 % CI). Every insurance type was significantly less likely to undergo surgery compared to City Contract. All except Medicaid, were more likely to undergo radiation compared to City Contract. African Americans are more likely to undergo surgery (2.68 times, 2.01-3.56, 95% CI) and were less likely to have radiation or chemotherapy when compared Caucasians (0.25 times, 0.20-0.31 95% CI). Conclusions: Disparities in race and insurance type can affect the stage at presentation, type of treatment received and survival.[Table: see text]
Effect of core needle biopsy number on intraductal carcinoma diagnosis in patients with metastatic castration-sensitive prostate cancer.
Authors: Kato Masashi , Tsuzuki Toyonori , Yamamoto Akiyuki , Fujita Takashi , Gotoh Momokazu
Published: February 2020

243

Background: The number of core needle biopsies performed to diagnose metastatic prostate cancer are sometimes reduced in daily clinical practice. Intraductal carcinoma of the prostate (IDC-P) is associated with adverse prognostic parameters and has recently received attention as a valuable indicator for the prediction of disease severity. Currently, the relationship between IDC-P diagnosis and the number of core prostate biopsies is unclear. In the present study, we analyzed the effect of core needle biopsy number on IDC-P diagnosis in patients with metastatic castration-sensitive prostate cancer. Methods: We retrospectively evaluated data from 150 patients diagnosed with metastatic prostate cancer at our hospital between 2002 and 2012. Percentage of the core involved with cancer and the maximum cancer occupancy were 100% in median of all the patients. Subjects were allocated to three groups according to the number of core biopsies performed: ≤5, 6–9, and ≥10. The study endpoints were the cancer-specific survival (CSS) and overall survival (OS) rates. Results: Twenty-seven (18%) patients had ≤5 core biopsies, 67 (45%) patients had 6–9 core biopsies, and 56 (37%) patients had ≥10 core biopsies. For patients who underwent ≥10 core biopsies, a significant difference on CSS was detected between with or without IDC-P ( p = 0.002). On the other hand, the difference decreased as the number of core biopsies became smaller (6–9; p = 0.322 and ≤5; p = 0.815). A similar trend was identified for the OS outcome. A significant difference on OS was also found between with or without IDC-P in patients who underwent ≥10 and 6–9 core needle biopsies ( p = 0.0002 and 0.015, respectively), but not in those who underwent ≤5 core biopsies ( p = 0.3407). IDC-P served as a stronger prognostic marker for CSS and OS than did the other factors included in the multivariate analysis. ( p = 0.0024, and p = 0.0014, respectively). Conclusions: Given the IDC-P detection and its value as a prognostic marker, we recommend the performance of ≥10 core biopsy procedures in patients diagnosed with metastatic prostate cancer. Sampling error effects the IDC-P value in smaller number of core needle biopsies.
Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer.
Authors: Narita Shintaro , Nomura Kyoko , Hatakeyama Shingo , Takahashi Masahiro , Sakurai Toshihiko , Kawamura Sadafumi , Hoshi Senji , Ishida Masanori , Kawaguchi Toshiaki , Ishidoya Shigeto , Shimoda Jiro , Sato Hiromi , Mitsuzuka Koji , Tochigi Tatsuo , Tsuchiya Norihiko , Ohyama Chikara , Arai Yoichi , Nagashima Kengo , Habuchi Tomonori ,   Michinoku Japan Urological Cancer Study Group
Published: February 2020

247

Background: The treatment strategy for patients with newly diagnosed metastatic hormone naïve prostate cancer (mHNPC) has changed in recent years. Thus, an accurate assessment of prognosis is critical. Conditional net survival provides the more appropriate method of estimating survival from cancer. The purpose of this study was to identify predictive factors associated with conditional net survival in patients with mHNPC initially treated with androgen deprivation therapy (ADT). Methods: The medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer-specific survival (CSS) and overall survival (OS) for up to five years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. Results: During follow-up (median, 2.95 years), 208 patients died, 169 from progressive prostate cancer. At baseline, the 5-year CSS and OS rates were 65.5% and 58.2%, respectively. The overall conditional 5-yearnet OS rate at baseline was 0.582, and the overall conditional 5-year net OS rates for patients who survived for1, 2, 3, 4, and 5 years were 0.566 (−0.16), 0.615 (+3.3), 0.550 (−0.32), 0.702 (+1.2), and 0.811 (+2.29), respectively. Conditional 5-year net CSS and OS survival gradually increased for all the patients. In patients given a 5-year survivorship, the conditional 5-year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) ≥2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. Conclusions: The conditional 5-year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient’s risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5-year follow-up. Conditional net survival can play a role in clinical decision-making, providing intriguing information for cancer survivors.
TMPRSS2: ERG expression in prostate cancer—Imaging and clinicopathological correlations.
Authors: Fasulo Vittorio , Lazzeri Massimo , Corbetta Marinella , Paciotti Marco , Maffei Davide , Soldà Giulia , Domanico Luigi , Frego Nicola , Regis Federica , Diana Pietro , Asselta Rosanna , Buffi Nicolo' , Casale Paolo , Saita Alberto , Chiereghin Chiara , Lughezzani Giovanni , Zuradelli Monica , Hurle Rodolfo , Duga Stefano , Guazzoni Giorgio Ferruccio
Published: February 2020

284

Background: The TMPRSS2:ERG gene fusion (T:E) is found in up to 70% of prostate cancers (PCa) and results in androgen dependent overexpression of ERG, promoting tumor growth. The early identification of T:E may be helpful even in low-risk PCa. Although T:E can be non-invasively detected in urine, its correlation with new imaging tools (MRI and high-frequency ultrasound) and clinical outcome remains vague.This study investigates T:E expression in patients scheduled for random/software-assisted MRI or micro-ultrasound (29Mhz) fusion biopsy. Methods: This is a prospective cohort study in patients with suspected PCa enrolled between 2016 and 2019, approved by local authorities with Prot. N. 336/19, 14/05/2019. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they had ³1 suspicious lesion (PI-RADS V.2 >2) at mpMRI or PRIMUS >2 at MICRO-US. For each patient, 1 prostatic core from the highest PI-RADS or PRIMUS lesion was collected for T:E analysis (a core from the right lobe in negative patients). Histological analyses were performed by experienced genitourinary pathologists. RNA was extracted from a dedicated fresh biopsy and RT-PCR was performed with different primer couples to detect the most frequent T:E fusions. All amplified products were checked by sequencing. Results: The cohort consists of 92 patients (median PSA 7.13 ng/ml, IQR 5.25-11.04 - average age 65ys), 81 with a diagnosis of PCa after biopsy. mpMRI was performed on 63 (68.5%) patients and was positive in 58 (92%), who underwent fusion biopsy. T:E fusion transcripts were detected in 23.5% of individuals with a diagnosis of PCa. Among patients positive for T:E, those analyzed by MRI were 100% positive (73% PI-RADS ≥4), those analyzed by MICRO-US were 83% positive. Sensitivity of the T:E assay for any PCa was 23.5%, specificity 100%, with negative and positive predicting values of 15% and 100%. There was no correlation between T:E and family history, PSA, PIRADS, PRI-MUS and Gleason score. Conclusions: Our finding showed a 100% of specificity making T:E an attractive tool for early cancer detection. In the future, identification of T:E in semen could represent a screening test for clinical stratification of patients with suspected PCa.
Characterization of PSMA and 18F-fluciclovine transporter gene expression in localized prostate cancer.
Authors: Chu Carissa , Alshalalfa Mohammed , Sjöström Martin , Zhao Shuang , Herlemann Annika , Chou Jonathan , Mahal Brandon Arvin Virgil , Kishan Amar Upadhyaya , Spratt Daniel Eidelberg , Karnes Jeffrey , Small Eric Jay , Wong Anthony C. , Porten Sima P. , Hope Thomas , Davicioni Elai , Nguyen Paul L. , Carroll Peter , Schaeffer Edward M. , Feng Felix Y , Cooperberg Matthew R.
Published: February 2020

295

Background: While 18F-fluciclovine PET/CT is approved in the US and recommended by the NCCN, prostate-specific membrane antigen (PSMA) PET/CT is more common in Europe/Australia and recommended by the EAU. Less is known about the biology of lesions detected by either modality. 18F-fluciclovine PET relies on radiotracer uptake by amino acid transporters LAT1-4 and ASCT1-2. PSMA PET is dependent on surface expression of PSMA. We compared relative expression of PSMA and fluciclovine transporter genes in radical prostatectomy (RP) samples to determine their distribution across subtypes and correlation with outcomes. Methods: Gene expression data of 19,102 RP samples were analyzed using the Affymetrix Human Exon 1.0 ST microarray. 1,135 patients had long term follow up. Associations between expression of PSMA and fluciclovine transporter genes (LAT1-4 and ASCT1-2) and pathologic variables, molecular subtypes, and clinical outcomes were conducted. Results: All fluciclovine transporter genes (LAT 1-4, ASCT1-2) were expressed at lower levels than PSMA (p <0.0001). PSMA expression was positively correlated with genomic risk score and pathologic Gleason score (p<0.0001), but LAT2-3 and ASCT2 were inversely correlated with genomic risk in primary tumors (p<0.0001) and less expressed in GS 9-10 tumors (p<0.0001). PSMA expression was associated with worse metastasis-free survival (MFS) (HR 1.45, p=0.001) and lymph node involvement (HR 2.14, p<0.0001). Expression of LAT2, LAT3, ASCT2 expression was associated with better MFS (HR 0.85, 0.63, 0.74, p<0.0001-0.04). After multivariable adjustment, PSMA expression remained independently prognostic of poorer MFS (HR 1.3, p=0.028). Luminal B subtype was notable for PSMA overexpression; Luminal A was enriched in ASCT2 and LAT2 (p<0.0001). PSMA expression did not correlate with ERG fusion prostate cancers, but LAT2, ASCT1, and ASCT2 were overexpressed in ERG fusion negative tumors (p<0.0001). Conclusions: PSMA expression is associated with more aggressive disease and poorer clinical outcomes than fluciclovine transporter genes in localized prostate cancer. Molecular subtypes of prostate cancer vary in PSMA and fluciclovine transporter gene expression.
Disparities in receipt of molecular imaging in biochemical recurrent prostate cancer.
Authors: Borno Hala , Lin Tracy Kuo , Odisho Anobel Y. , Desai Arpita , Koshkin Vadim S , Werner Kalin , Legaspi Nichole , Bell Alexander , Hope Thomas
Published: February 2020

297

Background: Molecular imaging with novel radiotracers is changing treatment landscape in prostate cancer (PCa). Currently, standard of care includes both conventional and molecular imaging, leaving uncertainty in prescription decision. This study evaluated the determinants of and disparities in utilization of molecular imaging for biochemical recurrent (BR) PCa. Methods: This is an observational, single institution, cohort study within the University of California, San Francisco (UCSF). Data were obtained on all men with BR PCa seen at UCSF from June 2018 to May 2019, regardless of histologic subtype. Multivariate logistic regression models were employed to analyze the primary outcome: receipt of molecular imaging (e.g. Fluciclovine PET, Prostate Specific Membrane Antigen PET) as part of diagnostic work-up for BR PCa. Multivariate linear regression models were used to analyze the secondary outcome: overall healthcare cost (hereafter cost) within a one-year time-frame. Results: The study sample included 245 patients; 88% non-Hispanic White (White), 2 % non-Hispanic Black (Black), 9% Asian/Pacific Islander (Asian), and 10% Other. The majority were 55 years or older (66%) and privately insured (73%). Analysis indicated that a one unit reduction in PSA is associated with 1.4 times higher likelihood of receiving molecular imaging (p<0.01). Analysis found that privately insured patients experienced approximately $500,000 more in cost (p<0.01) as compared to the publicly insured. Additionally, a one unit increase in PSA is associated with $5,075 increase in cost (p<0.05). Correlations between race and imaging type and having received radical prostatectomy (RP) and imaging type were identified but were not statistically significant (p<0.10). Conclusions: Higher PSA was associated with lower likelihood for molecular imaging and higher cost in a one year time-frame. Higher cost was also associated with private insurance, but there was no clear relationship between insurance type and imaging type. This study identified several factors – which may impact prescription pattern – that are worth exploring within a larger patient sample; namely, race/ ethnicity and RP as determinants for receipt of molecular imaging.
The Personalized Medicine for Prostate Cancer (PMPC) Study: The role of race, genomics, and patient complexity in treatment outcomes.
Authors: Greenfield Sheldon , Uchio Edward M. , Litwin Mark S. , Gin Gregory , Garraway Isla , Daskivich Timothy J. , Garland Harwood , Kaplan Sherrie H.
Published: February 2020

302

Background: Matching of patients with optimal treatment for localized prostate cancer (PCa) requires accurate estimates of risk for progression or recurrence. Traditional risk assessment methods may underestimate risk for certain patient subgroups, (e.g. minorities). In the PMPC study, we replicated an expanded risk model, adding genomic data to improve risk prediction and optimize treatment assignment for PCa. Methods: A prospective cohort of 660 patients with early PCa was identified from 3 teaching hospitals and 2 VA Hospitals in Southern California. Risk model data were collected from electronic medical records, patient questionnaires and tissue-based genomic data provided by GenomeDx. Complexity variables included demographic characteristics, clinical markers (PSA levels, Gleason score), patient-reported health status measures (e.g. comorbidity burden, depression, stress) and Decipher score. We compared individual components of the complexity score for 425 Non-Hispanic White (NHW) and 104 African American (AA) men using t-tests. Composite complexity scores were derived from weights from general linear models. Mean complexity scores were compared using t-tests. Results: Compared with NHW men, AA men had statistically significantly more comorbidity, poorer health ratings, poorer physical functioning, more depression, less energy, more fatigue, more stress and less resilience. More AA men had Gleason scores >6 (60.0%) than NHW men (46.6%), p=.0134. Fewer AA men (41.5%) had ‘low risk’ Decipher scores compared to NHW men (53.8%). More AA men had high complexity scores compared with NHW men (63.4% vs. 45.1%, p=.008), however, there were no statistically significant differences in the proportion of NHW vs. AA men on active surveillance, 46.0% vs. 40.7%, p=.384. Using clinical variables alone there were no significant differences in low risk between NHW and AA men. Conclusions: The addition of genomic data improved the complexity model developed earlier. AA men may be at higher risk for suboptimal treatment than predicted by clinical variables alone. Data from the longitudinal cohort will test accuracy of model prediction for disease progression or recurrence. Clinical trial information: NCT03770351.
A prospective study evaluating oral-only hormonal therapy with radiation for intermediate or high-risk prostate cancer in men age ≥ 70 years or with moderate comorbidity.
Authors: Onderdonk Benjamin Ernst , Dorn Paige L. , Arif Fauzia , Golden Daniel William , Karrison Theodore , Pitroda Sean P. , Szmulewitz Russell Zelig , Liauw Stanley L.
Published: February 2020

303

Background: Androgen deprivation therapy (ADT) improves disease control in intermediate (IR) and high risk (HR) prostate cancer (PCa) treated with radiation therapy (RT), but also causes toxicity which may be worse in men of older age or with comorbidity. We hypothesized that dual agent ADT, replacing GnRH agonist for an oral 5-alpha-reductase inhibitor (5AR), would improve hormonal health-related quality of life (HRQOL) without compromising PCa outcomes. Methods: Patients with localized IR or HR PCa, age > 70 years and/or with Charlson comorbidity index (CCI) score > 2 were treated with bicalutamide and finasteride or dutasteride (oADT). A synchronous standard of care (SOC) cohort received bicalutamide and GnRH agonist. Median RT dose was 78 Gy. Dual agent ADT was given for 4 months (mo), while 5AR or GnRH agonist continued for an additional 2 years. The primary endpoint was the Expanded Prostate Cancer Index Composite (EPIC-26) hormonal HRQOL global score at 6 mo, with success defined as < 30% decline, requiring 40 men in the oADT group. Secondary endpoints included a log-rank comparison of freedom from biochemical failure (FFBF), and overall survival (OS). Results: Between 1/2011 and 8/2018, 40 and 30 men were prospectively enrolled in the oADT and SOC cohorts, respectively, with similar CCI scores > 2 (73% vs 66%, p=0.58), and age (mean 71, p=0.99). Median follow-up was 36 mo. Global scores for hormonal HRQOL at baseline, 6 mo, and 2 yr were 89, 88, 84 for the oADT group, and 92, 81, 83 for the SOC group; the declines from baseline to 6 mo (p=0.04) and 2 yr (p=0.05) were smaller in the oADT group. Sexual HRQOL was better preserved at 6 mo (p<0.01) in the oADT group, which maintained higher testosterone at 2 years (452 vs 44, p<0.01). There were no differences in urinary or bowel HRQOL. The 3-year FFBF was 90% vs 96% (p=0.83) and OS was 83 vs 86% (p=0.77) between the oADT and SOC groups, respectively. Conclusions: oADT improves hormonal and sexual HRQOL compared to SOC ADT in men age ≥ 70 or moderate comorbidity treated with RT. These groups could be further evaluated in a randomized comparison; post-ADT RNA expression to evaluate the relative biologic effects will be performed. Clinical trial information: NCT01342367.
A prospective comparison of MRI-planned versus CT-planned radiotherapy for prostate cancer.
Authors: Schmidt Daniel R , Bhagwat Mandar , Glazer Daniel I. , Chen Ming-Hui , D'Amico Anthony Victor
Published: February 2020

312

Background: Chronic rectal toxicity significantly decreases the quality of life for men who receive radiotherapy for prostate cancer. The volume of rectum exposed to 70 Gy or more is a validated metric that predicts the risk of late rectal toxicity. We hypothesized that MRI as compared to CT-based prostate radiotherapy treatment planning can reduce the volume of rectum exceeding 70 Gy. Methods: This prospective study single arm study enrolled 15 men treated with external beam radiation therapy for localized prostate cancer. At the time of treatment planning a 3 Tesla T2-weighted magnetic resonance imaging examination of the prostate was obtained. A radiotherapy plan was designed by a medical physicist using identical constraints for both CT and MRI-based consensus volumes defined by a radiologist and radiation oncologist. The volume of rectum exposed to 70 Gy or more was calculated and compared using the paired Signed Rank Test. Results: The median age was 70 years (range 56-84), median PSA 7.3 ng/mL (range 3.2 – 22.1), and median prostate volume 40 mL (range 25 - 65) by transrectal ultrasound. Sixty percent (n=9) were intermediate risk and 40 percent (n=6) high risk by NCCN guidelines. The majority were either clinical stage T1c (n=7) or T2 (n=6). Two men had extracapsular extension (T3a). None of the participants had seminal vesicle invasion (T3b), rectal or bladder involvement (T4), or lymph node metastasis (N1). All 15 men enrolled on the study completed both a standard radiation planning CT and research MRI examination. For CT-based treatment plans the median volume of rectum receiving 70 Gy or more was 9.3 cubic centimeters (cc) [IQR 7.0 to 10.2] compared with 4.9 cc [IQR 4.1 to 8.7] for MRI-based plans. This resulted in a median volume reduction of 2.1 cc [IQR 0.5 to 5.3, P < .001]. Conclusions: MRI-planned prostate radiotherapy can reduce the volume of rectum receiving radiation doses in excess of tolerance (70 Gy or more) and should be considered in men who are at high risk for late rectal toxicity. Clinical trial information: NCT02470910.
Risk of secondary sarcoma after abdominopelvic cancer treatment: Results from a contemporary cohort.
Authors: Hird Amanda Elizabeth , Matta Rano , Magee Diana E. , Kulkarni Girish S. , Kodama Ronald , Herschorn Sender , Nam Robert
Published: February 2020

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Background: Our objective was to explore the risk of sarcoma in a large cohort of patients with localized abdominopelvic cancer treated with radiotherapy (RT) compared to surgery. The risk of other secondary non-sarcoma solid organ tumors was also explored. Methods: This is a population-based retrospective cohort study examining the risk of sarcoma in patients with localized prostate, bladder, colorectal, cervical, uterine, and testis cancer between January 1, 2002-December 31, 2016. Multivariable Cox proportional hazard analysis was used to compare time from primary treatment (radical surgery or RT) to second cancer, adjusting for age, comorbidity, income quintile, and rurality, accounting for death as a competing risk. The standardized incidence rate (SIR) was calculated as the ratio of the observed divided by the age- and sex-stratified expected number of sarcoma cases from the Ontario population. Results: 173,580 patients were included (79,662 underwent surgery and 93,918 underwent RT). Most patients had genitourinary (51.4%) or colorectal cancer (39.9%) and 24.4% received chemotherapy. Overall, 332 sarcomas developed over a median 5.7 years (IQR: 2.2-8.9) and were more common in the RT group (239/93918 [0.3%]) compared to the surgery group (93/79662 [0.1%], p<0.001). RT exposure (unadjusted HR=2.67, 95%CI:2.10-3.40, p<0.001, adjusted HR=2.59, 95%CI:2.03-3.31, p<0.001) and perioperative chemotherapy use (HR=1.31, 95%CI:1.03-1.69, p=0.038) were associated with an increased relative rate of sarcoma. Patients who received RT had an increased risk of sarcoma compared to the general population (SIR=1.46, 95%CI:1.12-1.90, p=0.005). For our secondary outcome, patients who received RT had an increased hazard of developing a second non-sarcoma solid malignancy compared to patients who underwent surgery (HR=1.16, 95%CI:1.10-1.22, p<0.001). Conclusions: This is the largest cohort investigating sarcoma in patients with abdominopelvic cancer. Patients treated with RT have a markedly increased risk of sarcoma compared to the general population. RT was an independent risk factor for sarcoma and non-sarcoma second malignancy.
Evaluating the tolerability of a simultaneous focal boost to the gross tumor in prostate SABR: A toxicity and quality-of-life comparison of two prospective trials.
Authors: Alayed Yasir , Davidson Melanie , Chu William , Liu Stanley K. , Tseng Chia-Lin , Cheung Patrick , Vesprini Danny , Chung Hans T. , Morton Gerard , Musunuru Hima Bindu , Ravi Ananth , Korol Renee , Deabreu Andrea , Commisso Kristina , Bhounr Zeeba , D'alimonte Laura , Mittmann Nicole , Dragomir Alice , Zhang Liying , Loblaw Andrew
Published: February 2020

319

Background: Dose-escalated SABR to the whole prostate may be associated with better outcomes, but at a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on MRI. We report the toxicity and quality of life (QOL) outcomes of two phase II trials of prostate and pelvic SABR, with or without a simultaneous DIL boost. Methods: The first trial treated patients with high-risk prostate cancer (PCa) to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk PCa to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities and QOL were assessed. Results: 30 patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 GI or GU toxicity between the two trials, or cumulative worst late GI or GU toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the two trials. Conclusions: Prostate and pelvic SABR with a simultaneous DIL boost was feasible and did not lead to a significant change in toxicity or QOL when compared to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes. Clinical trial information: NCT02911636.
Real-world analysis of prostate-specific antigen (PSA) outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide (ENZA).
Authors: Freedland Stephen J. , Schultz Neil M. , Coutinho Anna D. , Fuldeore Rupali , Hedlund Nancy , Feng Qi , Ramaswamy Krishnan , Hong Agnes
Published: February 2020

33

Background: ENZA showed efficacy in chemotherapy-naïve men with mCRPC in a clinical trial setting (PREVAIL). We report real-world outcomes with ENZA for this population in a urology practice setting. Methods: This retrospective cohort study included men with prostate cancer newly initiating ENZA in the IntrinsiQ Specialty Solutions™ urology electronic medical records database between September 1, 2014 and February 28, 2018. Due to the approved indication in the study time frame, prescription of ENZA (first claim date = index date) was used as a proxy for mCRPC. Patients with evidence of prior chemotherapy and/or abiraterone were excluded. PSA value closest to index date (±30 days) was used as baseline. Men were followed until the earliest of: discontinuing ENZA, leaving practice, death, or study end. Best PSA response (largest decline or smallest increase in absence of decline from baseline), PSA declines of ≥50% and ≥90%, undetectable PSA, and time to PSA progression were analyzed. Results: We identified 931 eligible men. Most (>95%) were ≥60 years old; hypertension (54.6%) and diabetes (17.0%) were the most common comorbidities. Median (interquartile range [IQR]) baseline PSA was 9.0 (2, 37) ng/dL. Median (IQR) follow-up time was 12.5 (7.6, 19.4) months, during which a median (IQR) of 4 (3, 6) PSA tests were observed. Median time between two adjacent PSA tests was 2.0 months. A ≥50% and ≥90% PSA decline was observed in 55.0% and 23.8%, respectively. Best PSA response was a median (IQR) PSA decline of 58% (-89%, 1%), with 14.2% reaching an undetectable PSA value. Median time to PSA progression was 18.5 months (95% confidence interval 15.6, 23.7). Conclusions: This real-world study supports the effectiveness of ENZA in patients with mCRPC. The median PSA at treatment was much lower than PREVAIL, potentially explaining the longer time to PSA progression vs. PREVAIL. However, a lower proportion had PSA declines of ≥50% and ≥90% vs. PREVAIL, which may be attributed to more frequent PSA monitoring within a clinical trial setting and thus more opportunity to capture the true best PSA response.