bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient opinions on controversies: In regard to low-risk prostate cancer, is Gleason 6 the old Gleason 5?
Authors: Wolinsky Howard , Schraidt James , Lichty Mark , Segal Philip , Berlin Alejandro , Siddiqui Mohummad Minhaj , Washington Samuel L. , Geller Herbert M. 
Published: March 2023

329 Background: In 2005, the International Society of Urologic Pathology effectively eliminated Gleason patterns 1 and 2, thus removing Gleason grades 2-5 as a cancer diagnosis. Today, patients with low-risk Gleason 6 prostate cancer, prostate cancer clinicians, guideline writers, and policymakers are facing issues about whether Gleason 6 lesions should be reclassified as noncancer. Some of the issues being discussed among urologists, radiation oncologists, and pathologists focus on whether to reclassify low-risk Gleason 6 prostate lesions as a noncancer with the goal of reducing patient anxiety and financial toxicity. We also asked about biopsy methods, which affects both the low-risk and favorable intermediate-risk populations, that have been a major topic in support organizations over the past two years. We conducted this survey of patients on active surveillance to determine where patients stand on these issues to help guide clinicians, policymakers, and guideline writers. Methods: We conducted a survey in October 2022 asking patients their views on these issues. We invited patients on active surveillance or previously on active surveillance for low-risk prostate cancer to respond to a 40-question survey to share their views on a range of topics related to the diagnosis of Gleason grade 6 lesions as cancer, as well as complementary issues related to innovations in biopsy and active surveillance. We had access to email lists containing ~2,500 names from the AnCan Foundation’s Active Surveillance Virtual Support Group, Active Surveillance Patients International, Prostate Cancer Support Canada, and The Active Surveillor newsletter. Other major prostate cancer support groups also distributed links to the questionnaire posted on SurveyMonkey. Results: At the deadline for placeholders for abstracts, the survey is underway. Questions for patients include: Have you experienced distress (anxiety or depression) because of the cancer label from Gleason 6? Have you experienced financial toxicity, including cancellation of insurance policies or an increase in rates, because of the cancer diagnosis? If Gleason 6 was reclassified as a noncancer, would you stop surveillance? What will you prefer as a next biopsy--transperineal to avoid the risk of sepsis and other infections or transrectal which may cause less immediate pain? Conclusions: We intend that the results will inform decision making as to the classification of Gleason 6 diagnoses.
Validation of baseline health-related quality of life as prognostic indicator for survival outcome in men with intermediate risk prostate cancer undergoing radical prostatectomy.
Authors: Westhofen Thilo , Buchner Alexander , Schlenker Boris , Becker Armin , Stief Christian G. , Kretschmer Alexander 
Published: March 2023

340 Background: Accurate prediction of cancer outcomes remains a key component of prostate cancer (PC) treatment decision-making. Intermediate-risk PC patients represent a heterogeneous group with highly variable prognoses and it is challenging to provide uniform treatment recommendations for those patients. Previous studies have shown baseline health-related quality of life (HRQOL) to be a robust prognostic indicator for survival outcomes of different cancer entities in the metastatic setting, with scarce evidence on PC. We therefore sought to validate the predictive value of baseline HRQOL for survival outcomes in men with intermediate risk PC undergoing radical prostatectomy (RP). Methods: We identified 4780 patients with intermediate risk PC according to NCCN risk stratification and prospectively assessed baseline HRQOL prior RP. Patients were stratified by global health status (GHS) domain of the QLQ-C30 questionnaire. Oncologic endpoints were metastasis-free survival (MFS) and overall survival (OS). Multivariable Cox regression models were applied to assess the predictive value of baseline GHS on survival outcomes. Harrell's discrimination C-index was applied to calculate the predictive accuracy of the model. Decision curve analysis (DCA) was performed to validate the clinical net benefit associated with adding GHS to our multivariable model ( P < .05). Results: Median follow up was 51mo. In multivariable analysis, GHS was confirmed as an independent predictor for increased MFS (HR .98, 95% CI .97-.99; P = .028) and OS (HR .97, 95% CI .95-.99; P = .008), indicating a relative risk reduction of 1.7% for MFS and 2.8% for OS per 1-point increase of baseline GHS. Adding GHS to our model improved predictive accuracy of prognosis for MFS by 6% (c-index .75 vs .72) and for OS by 8% (c-index .78 vs .74). Validation with DCA revealed a net benefit over all thresholds in prediction of MFS and OS when adding GHS to our model. Conclusions: Our findings highlight that baseline HRQOL is a valuable and robust prognostic factor for patients with intermediate-risk PC prior RP. Baseline HRQOL data improve prognostic accuracy of MFS and OS and can therefore support treatment decision-making. [Table: see text]
Development and validation of a multi-institutional nomogram of outcomes for PSMA-PET–based salvage radiotherapy in recurrent prostate cancer.
Authors: Zamboglou Constantinos , Arnoux Armelle , Janbain Ali , Strouthos Iosif , Farolfi Andrea , Koerber Stefan , Peeken Jan , Vogel Marco , Ferentinos Konstantinos , Shelan Mohamed , Grosu Anca L. , Kroeze Stephanie , Guckenberger Matthias , Fanti Stefano , Hruby George , Scharl Sophia , Wiegel Thomas , Henkeberens Christoph , Emmett Louise , Hegemann Nina-Sophie 
Published: March 2023

355 Background: We aimed to develop and to validate a multi-institutional nomogram of outcomes for PSMA-PET based salvage radiotherapy (sRT) following radical prostatectomy (RP) for patients with recurrent or persistent prostate cancer (PCa). Methods: Data from patients with a detectable post-RP prostate-specific antigen (PSA) treated with sRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 11 academic institutions from 5 countries. All patients had a PSMA-PET scan prior sRT and patients with distant metastases on PET were excluded from this analysis. The freedom from biochemical failure (FFBF) rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse (BR) was defined as PSA nadir +0.2 ng/ml after sRT. Results: Overall, 1029 patients (training set n=821, external validation set n=208) with a median follow-up of 33 months were included. On PSMA-PET, 427 (42%) and 313 (30%) patients had local and nodal recurrences, respectively. Elective pelvic lymphatics were irradiated in 368 (36%) patients. All patients received sRT to the prostatic fossa receiving a dose of <66 Gy, 66-70 Gy and >70 Gy in 103 (10%), 551 (54%) and 375 (36%) patients, respectively. Androgen deprivation therapy (ADT) was given in 325 (32%) patients. On multivariable Cox regression analysis, pre-SRT PSA, ISUP grade, pT stage, surgical margins, ADT use, sRT dose and nodal recurrence on PSMA PET were associated with FFBF. The nomogram concordance index was 0.7 for FFBF in external validation. Conclusions: We present an externally validated contemporary nomogram which can estimate individual patient outcomes after PSMA-PET guided sRT. Positive lymph nodes on PSMA-PET seem to be a new risk factor for BR after sRT.
Biochemical disease control outcomes of stereotactic body radiation therapy (SBRT) or moderate hypo-fractionation (HFRT) for low- and intermediate-risk prostate cancer (PrCa): Retrospective analysis of 12 years of experience at two Canadian cancer centers.
Authors: Hu Hsin-pei (Spencer) , Gouran-Savadkoohi Mohammad , Anagnostopoulos Gregory , Dayes Ian S. , Ishkanian Adrian , Hallock Abhirami , Corbett Thomas B , Lukka Himanshu , Quan Kimmen , Schnarr Kara , Cuthbert David , Goldberg Mira , Tsakiridis Theodoros 
Published: March 2023

363 Background: SBRT uses highly conformal radiotherapy to deliver high dose per fraction treatment. Advantages of SBRT include short treatment times, decreased costs and limited toxicity. Randomized trial outcomes of 7-fraction SBRT for low or intermediate PrCa were reported but results of studies that compared 5-fraction SBRT with conventional and HFRT are pending. Here, we reviewed the 12-year experience with SBRT and HFRT at the Juravinski and Walker Family Cancer Centers in Ontario. Methods: We reviewed patients with low or intermittent-risk PrCa treated with SBRT alone or HFRT alone in the period of July 2010 and February 2022. Database search criteria included treatments with SBRT 35-40Gy in 5 fractions and HFRT 60-62Gy in 20 fractions. Overall survival (OS), time to biochemical failure (per Phoenix criteria: i.e., 2ng/mL above PSA nadir) and biochemical failure-free survival (bFFS) were reviewed. Kaplan-Meier curves were used to assess OS and bFFS. Results: We identified 314 patients with low or intermediate-risk PrCa who were treated with SBRT and 258 patients who were treated with HFRT. Intermediate-risk category composed 86.0% and 95.7% of the SBRT and HFRT cohorts. ISUP Grade Group (GG) distributions for the SBRT and HFRT patients were: GG1: 19.4% and 9.3%, GG2: 72.9% and 74.0%, and GG3: 7.6% and 16.7%, respectively. OS rates at 5 years were 96.6% for SBRT vs. 95.8% for HFRT-treated patients. The 5-year bFFS rates for SBRT and HFRT were 92.3% and 90.1%, respectively. The 7-year bFFS rate for the SBRT cohort was 90.2%. Mean time to biochemical failure was 40.4 months after SBRT vs. 35.8 months after HFRT. Conclusions: SBRT is an effective treatment option for low to intermediate-risk PrCa with encouraging OS and bFFS rates comparable with HFRT. Pending randomized trial results will determine whether SBRT is the new standard of care for this population.
Stereotactic reirradiation for local prostate cancer recurrence: Mono-institutional experience of 108 patients.
Authors: Baty Manon , Castelli Joel , Gnep Khemara , Delaby Nolwenn , Mathieu Romain , de Crevoisier Renaud 
Published: March 2023

365 Background: The aim of this study was to report the efficacy and toxicity of salvage stereotactic body radiation therapy (SBRT) for local prostate cancer recurrence after radiotherapy. Methods: We retrospectively reviewed a total of 108 medical records of patients treated with salvage SBRT for prostate cancer recurrence, between July 2015 and February 2021 in our institution. Patients who had initial radical prostatectomy were excluded. The median time interval between the two radiation treatments was 9 years (range, 3-20 years). All the patients had biochemical recurrence, with a PSA of 3.5 ng/mL (range, 1.8-43 ng/mL). Local recurrence was to be proven by biopsies, without distant lymph node or metastasis. The local recurrence was visible in 82% and 99% of patients on mpMRI and choline/PSMA PET/CT, respectively. The salvage treatment consisted in SBRT at a total dose of 36 Gy in six fractions delivered every other day, associated with androgen deprivation therapy in 44% of patients. We reported efficacy and toxicity (according to CTCAE v 4.03 classification) after salvage SBRT. Results: Median follow-up was 19.6 months (range, 2.3-67 months). Two year biochemical recurrence-free survival and lymph node/metastases free survival rates were 76% (95% CI: 66-87%) and 88% (95% CI: 80-96%), respectively. Regarding acute toxicity, rates of grade 2 and 3 GU toxicities were 27% and 2%, respectively. Rate of grade 2 GI toxicity was 2%, without grade ≥3. Regarding late toxicity, 2 year rates of grade 2 and 3 GU toxicities were 50% (95% CI: 44-56%) and 8% (95% CI: 2-14%), respectively. One patient experimented a grade 4 GU toxicity (bladder necrosis requiring a cystectomy) 8 months after SBRT. Two year rate of grade 2 GI toxicity was 2 (95% CI: 0-5%), without grade ≥3. Conclusions: The main toxicity of prostate salvage SBRT is GU. With a short follow-up, a subset of patients may be controlled by the salvage treatment.
Societal benefits of surrogate outcomes to support reimbursement decisions: The case of prostate cancer.
Authors: de Feria Cardet Rafael , Davis Ian D. , Haas Marion , Laba Tracey-Lea , Goodall Stephen , De Abreu Lourenço Richard 
Published: March 2023

372 Background: Incorporating surrogate outcomes for survival into economic evaluations for localized prostate cancer (LPC) has the potential to reduce the time needed to subsidise new therapies but may increase uncertainty regarding true benefit. The ICECaP study demonstrated that metastasis-free survival (MFS) is a strong surrogate of overall survival (OS) in LPC. We sought to model the benefits to society of earlier funding decisions, and to understand the context of societal trade-offs between aspects of drug value and time to reimbursement decision-making in LPC. Methods: Societal benefits were modelled using a 4-health state (biochemical recurrence (BCR), BCR-free, metastasis and death) partitioned survival model to evaluate the cost-effectiveness of abiraterone plus prednisolone (AAP) plus standard of care (SoC) compared to SoC alone in LPC. Survival outcomes were dependent on the ICECaP surrogacy relationship. Treatment pathways and costs reflected Australian practice and quality of life was informed by the literature. The model evaluated the difference between deciding to reimburse AAP now, based on MFS, versus wait for OS 3 years. Societal trade-offs were captured using a population based discrete choice experiment exploring the influence on preference for drug reimbursement of cost-effectiveness, cost to Government, adverse events, proportions expected to benefit, nature of benefits, the completeness of data and the time of follow-up. Preferences were analysed using mixed logit analyses. Results: The analysis of societal benefits showed that using MFS as a surrogate for OS could prevent 117 patients from recurrence, 30 from metastases and save 63 lives in the short-term when AAP is compared with SoC for LPC patients in Australia. Delaying the reimbursement decision for 3 years results in a loss of 4.48 years, 0.47 quality adjusted life years, and increase the cost to $11,558 per patient over the lifetime. The analysis of societal trade-offs reflected results from 1,003 community members and showed an inclination to favour reimbursing interventions that benefit a high proportion of patients (OR=2.10 CI 95%=1.91, 2.32), have a lower cost-effectiveness ratio (OR=0.81 CI 95%= 0.78, 0.88) and an aversion for evidence from ongoing studies (OR= 0.83 CI 95%= 0.78, 0.88). Conclusions: Using MFS as surrogate for funding decision in LPC is likely to produce benefits to society in terms of improved short and long-term outcomes. This contrasts with societal preferences to delay reimbursement decisions to increase certainty. This suggests, improved cost-effectiveness could be used to compensate for the uncertainty arising from the use of surrogate outcomes in reimbursement decisions. The use of evidence-based surrogate outcomes in economic evaluations to support reimbursement decisions can reduce the time it takes new interventions to become available improving the benefits to society.
Detection of intraductal carcinoma of the prostate (IDCP) cases focusing on high-grade prostatic intraepithelial neoplasia (PIN) findings regarding invasive carcinoma of the prostate.
Authors: Watanabe Ryuta , Sugihara Naoya , Kono Reina , Arai Osuke , Kakuda Toshio , Noda Terutaka , Nishimura Kenichi , Fukumoto Tetsuya , Miura Noriyoshi , Kurata Mie , Miyauchi Yuki , Kitazawa Riko , Haffner Michael C , Kikugawa Tadahiko , Saika Takashi 
Published: March 2023

379 Background: Intraductal carcinoma of the prostate (IDCP) is a pathological pattern that involves atypical cells proliferating within the normal gland where basal cells are preserved. These exhibit cribriform morphology, a finding associated with poor prognosis. In addition to the TMPRSS2-ERG fusion gene, TP53, RB1, and PTEN deletions, and SPOP and HRR gene mutations, such as a BRCA mutations, are frequently detected in patients with IDCP. The National Comprehensive Cancer Network (NCCN) guidelines suggest that early genetic testing should be considered. However, IDCP recognition is notably low, and diagnosis requires skill. Methods: We selected 98 cases with "prostate cancer with high-grade prostatic intraepithelial neoplasia (PIN) in the background" by referring to the pathology reports of cases who underwent total prostatectomy for prostate cancer at our hospital between November 2011 and November 2021. Twelve cases were narrowed down to those that were considered suggestive of IDCP based on the pathology reports and reviewed by three pathologists to determine the presence of IDCP. These were additionally reviewed by three pathologists for the presence or absence of IDCP and a gene test of prostatectomy specimens was submitted for the relevant cases to determine the presence or absence of HRR gene mutations. Results: Five of the twelve cases were determined to be IDCP positive. The Gleason score of background prostate cancer was 4+3 in 3 cases, 4+4 in 1 case, and 4+5 in 1 case. Median postoperative follow-up was 37 months (22- 45 months); 3 of the 5 patients had no recurrence, 1 had recurrence at 2 years and 3 months resulting in additional local radio therapy (RT), and 1 patient died of other causes. Pathology genetic testing identified HRR-related genetic abnormalities, including BRCA mutations. Conclusions: We were able to establish IDCP cases from past high-grade PIN cases. As a number of HRR gene mutations of unknown pathological significance were detected, IDCP cases could be retrieved from past cases and genetic abnormalities could be identified efficiently. The findings of the study provide a possible approach to diagnose prostate cancer cases with genetic mutations at an early stage.
Characterization of lymph node metastases in prostate cancer.
Authors: Gottlieb Josh , Choe Jane , Chang Shu-Ching , Krasne David , Hoon Dave S. B. , Wilson Timothy 
Published: March 2023

380 Background: Unlike lymph node (LN) staging in other malignancies, prostate cancer nodal staging does not characterize or quantify the LN tumor burden. Detailed characterization of LN metastases may provide improved prognostic information, which could assist in post-surgical management decisions. Methods: Clinical and pathologic information was retrospectively collected via electronic medical record from 66 patients with pathologically confirmed LN involvement after radical prostatectomy with pelvic lymph node dissection performed by a single surgeon. Tissue slides of all positive LNs were re-evaluated by a single pathologist in accordance with our institutional review board protocol. Poisson regression analyses and Cox proportional-hazard regression were performed to evaluate the association of risk factors with the number of positive nodes and the association of LN characteristics with biochemical recurrence (BCR)-free survival. Results: Median number of positive LNs per patient was 2 (IQR 1-3). Mean % positive LNs per patient was 8.9 (SD10.4). Mean cumulative size of all tumor deposits in all positive LNs per patient was 5.0mm (SD 4.8). Average % surface area of LN involved by tumor was 28%. 48 (73%) patients were alive without disease at median follow-up time of 38 months (IQR 26-50 months). Higher pre-surgery PSA, clinical stage T3-T4 versus T1-2, extraprostatic extension (EPE), seminal vesical involvement (SVI), and lymphovascular invasion (LVI) were significantly associated with higher incidence rate of nodal positivity. Larger mean size of largest LN deposits, mean size of total LN deposits, and mean % surface area of LN involved were significantly associated with worse BCR-free survival. There was no significant association for number of positive nodes, LN anatomical compartments, extranodal extension (ENE), span of ENE, and distance of ENE from LN capsule. Higher pre-surgery PSA and post-surgery Gleason grade were significantly associated with worse BCR-free survival. Conclusions: Our data shows that LN tumor burden is associated with worse BCR-free survival. Anatomical LN compartments and quantification of ENE did not show significant association with BCR. [Table: see text]
Polo-like kinase-1 as a potential prognostic marker of prostate cancer utilizing ORIEN data.
Authors: Nutalapati Snigdha , Wang Chi , Liu Alice X , Zhang Zhuwei , Colman Howard , Lam Elaine T. , Carpten John D. , Singer Eric A. , Adra Nabil , Devitt Michael Edward , Chahoud Jad , Tripathi Abhishek , Stratton Kelly Lynn , Myint Zin 
Published: March 2023

384 Background: Polo-Like Kinase-1(PLK1) is one of the key regulators in G2/M cell cycle. Preclinical studies have shown that PLK1 might be involved in treatment resistance in prostate cancer (PCa). PLK1 overexpression by immunohistochemistry is associated with higher Gleason grade and thus PLK1 could play a role in PCa tumorigenesis. In this study, we utilized a different methodology by using RNA-seq PLK1 expression and correlated with clinical outcomes. Methods: Patients with all stages of prostate adenocarcinoma diagnosed between 2014 and 2020 from nine participating members of the Oncology Research Information Exchange Network (ORIEN) were included in the study. Tumor RNA-seq was analyzed for PLK1 expression and associated with clinical data obtained from ORIEN AVATAR. PLK1 expression was stratified into high expression (defined as ≥75th percentile of PLK1 mRNA expression) vs. low expression (≤75th percentile). Univariate and multivariate Cox proportional hazard model were used to compare overall survival between patients with low vs high PLK1 expression adjusting for age, race, PSA and stage. Results: A total of 452 tumors were evaluated for PLK1 expression. Of those, 241 (53.3%) had high PLK1 and 211 (46.7%) had low PLK1 expression. Median age at diagnosis for high and low PLK1 expression was 64.5 and 63.2 years respectively. The majority of patients were Caucasian in both groups. In high PLK1 group, 93 (65%) had localized high risk/very high risk disease, 27 (19%) had localized intermediate risk, 20 (14%) had metastatic vs. 97 (63%), 38 (25%) and 18(12%) respectively in low PLK1 group. Gleason ≥ 8 and PSA <20 were seen slightly more in high PLK1 compared to low PLK1; 40% vs 33% and 96% vs.94% respectively. The median follow-up time was 2.74 years in low PLK1 group and 2.71 years in high PLK1 group. There was no difference between PLK1 low vs. high expression for age, race, stage, PSA and Gleason grade. There was no difference in overall survival between low PLK1 and high PLK1 expression by univariate analysis (p=0.86; HR 1.09) or after adjusting for multivariate analysis (p=0.85; HR 1.12). Conclusions: In our study, we did not find RNA-seq PLK1 expression as a potential prognostic marker for prostate cancer. There was no survival difference between low PLK1 vs. high PLK1 expression.