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Purpose/Objective: The optimal radiotherapy strategy for prostate cancer (PC) patients with high nodal risk remains debated. This prospective phase II study reports long‑term clinical outcomes, toxicity, and patient‑reported outcomes in men with PC treated with whole‑pelvis radiotherapy and dose escalation to MRI‑identified intraprostatic lesions and PET‑positive pelvic lymph nodes.

Materials/Methods: Eighty‑five PC patients with high nodal risk or up to three pelvic nodal metastases were enrolled between 2013 and 2017. Radiotherapy delivered 77 Gy to the prostate and 56 Gy to pelvic nodes in 35 fractions, with escalation to 70 Gy for PET‑positive nodes and 84 Gy for MRI‑defined intraprostatic lesions when feasible. Endpoints included biochemical progression‑free survival, overall survival, toxicity, and longitudinal patient‑reported outcomes.

Results: Seventy-eight patients underwent radiotherapy. Of these, 42 received an intraprostatic boost and were classified as the per-protocol population. Median follow‑up was 7.8 years, and 26% had N1 disease. For the full cohort, five‑year biochemical progression‑free survival was 76%, with poorer results among patients with RECIST‑positive nodal involvement. Five‑year overall survival was 95%. Acute grade ≥ 2 genitourinary and gastrointestinal toxicities occurred in 33 and 23%, respectively, and decreased over time. No grade ≥ 3 gastrointestinal toxicity was observed. Patient‑reported outcomes showed low long‑term urinary and bowel bother.

Conclusion: Whole‑pelvis radiotherapy with targeted dose escalation was well tolerated. The high proportion of patients not receiving an intraprostatic boost underscores methodological challenges and emphasises the need for standardised imaging interpretation and delineation guidelines.

Prostate cancer (PCa) is common world-wide. Current diagnostics based on testing for circulating levels of prostate specific antigen (PSA) is unspecific, and novel prognostic markers are needed for personalized therapeutic strategies. Pro-neuropeptide Y (pro-NPY) has been reported as a tissue marker for PCa related to poor prognosis. This study explored the prognostic value of circulating pro-NPY in PCa. Plasma samples were obtained from two patient cohorts: (1) men examined due to increased PSA levels in 2003–2011 (n = 796) and (2) patients treated for PCa in 2013–2016 (n = 92). Cohort 2 also provided plasma samples collected ~ 3 months after therapy. For plasma pro-NPY assessment, a sandwich immunoassay was developed. In cohort 1, 315 patients were diagnosed with PCa at the time for blood sampling, 137 were diagnosed during follow-up, and 344 remained disease-free. Plasma pro-NPY provided independent prognostic information from PSA regarding time to metastasis and PCa death. In cohort 2, high plasma pro-NPY levels were confirmed associated with metastatic disease and poor survival. Plasma pro-NPY levels were normalized after androgen-deprivation therapy, suggesting androgen-regulation. In conclusion, high circulating pro-NPY levels are associated with metastasis and poor outcome in PCa. Prospective validation is needed before suggesting pro-NPY for clinical use. The underlying biology and consequences of pro-NPY overexpression remain to be understood.

Background: High-risk prostate cancer is often treated with combined androgen deprivation therapy (ADT) and radiotherapy (RT). Blood biomarkers may enable treatments to be tailored to individual patients. Metabolomics, the study of small-molecule alterations in blood, is promising, and lipids are emerging as potential markers of poor prognosis. This study aims to investigate metabolic changes during prostate cancer treatment and their correlation to disease outcome.

Methods: This study included 136 blood plasma samples from 35 patients with high-risk prostate cancer treated with RT and ADT, recruited from the Uppsala/Umeå Comprehensive Cancer Consortium (U-CAN) project. Blood samples were collected before, during, and after treatment and analyzed at Metabolon Inc. (Durham, NC, USA). To study differences in metabolic levels during treatment, three different sampling time points were considered: before ADT, in-between ADT and RT, and after RT. Both multivariate (orthogonal projections to latent structures, OPLS) and univariate analyses were performed, where statistical significance in combination with a large fold change was considered indicative of a substantial change.

Results: Significant changes in metabolite levels were observed. Many of the significant metabolites for the whole course of treatment were also significant during ADT but not during RT, indicating that changes during ADT dominated the overall treatment. Changes were found to be especially common in steroids and fatty acids. Multivariate analysis revealed significant differences in metabolites between relapsing and non-relapsing patients. Among the significant metabolites were cholesterol and epiandrosterone.

Conclusions: Metabolomics can identify biomarkers for prostate cancer treatment response and relapse. Further studies are needed to identify patterns and individual metabolites to personalize treatment strategies for prostate cancer.

Background: Prostate cancer (PC) is a heterogenous multifocal disease ranging from indolent to lethal states. For improved treatment-stratification, reliable approaches are needed to faithfully differentiate between high- and low-risk tumors and to predict therapy response at diagnosis.

Methods: A metabolomic approach based on high resolution magic angle spinning nuclear magnetic resonance (HR MAS NMR) analysis was applied on intact biopsies samples (n = 111) obtained from patients (n = 31) treated by prostatectomy, and combined with advanced multi- and univariate statistical analysis methods to identify metabolomic profiles reflecting tumor differentiation (Gleason scores and the International Society of Urological Pathology (ISUP) grade) and subtypes based on tumor immunoreactivity for Ki67 (cell proliferation) and prostate specific antigen (PSA, marker for androgen receptor activity).

Results: Validated metabolic profiles were obtained that clearly distinguished cancer tissues from benign prostate tissues. Subsequently, metabolic signatures were identified that further divided cancer tissues into two clinically relevant groups, namely ISUP Grade 2 (n = 29) and ISUP Grade 3 (n = 17) tumors. Furthermore, metabolic profiles associated with different tumor subtypes were identified. Tumors with low Ki67 and high PSA (subtype A, n = 21) displayed metabolite patterns significantly different from tumors with high Ki67 and low PSA (subtype B, n = 28). In total, seven metabolites; choline, peak for combined phosphocholine/glycerophosphocholine metabolites (PC + GPC), glycine, creatine, combined signal of glutamate/glutamine (Glx), taurine and lactate, showed significant alterations between PC subtypes A and B.

Conclusions: The metabolic profiles of intact biopsies obtained by our non-invasive HR MAS NMR approach together with advanced chemometric tools reliably identified PC and specifically differentiated highly aggressive tumors from less aggressive ones. Thus, this approach has proven the potential of exploiting cancer-specific metabolites in clinical settings for obtaining personalized treatment strategies in PC.

Background: Prostate cancer (PC) can display very heterogeneous phenotypes ranging from indolent asymptomatic to aggressive lethal forms. Understanding how these PC subtypes vary in their striving for energy and anabolic molecules is of fundamental importance for developing more effective therapies and diagnostics. Here, we carried out an extensive analysis of prostate tissue samples to reveal metabolic alterations during PC development and disease progression and furthermore between TMPRSS2-ERG rearrangement-positive and -negative PC subclasses.

Methods: Comprehensive metabolomics analysis of prostate tissue samples was performed by non-destructive high-resolution magic angle spinning nuclear magnetic resonance (H-1 HR MAS NMR). Subsequently, samples underwent moderate extraction, leaving tissue morphology intact for histopathological characterization. Metabolites in tissue extracts were identified by H-1/P-31 NMR and liquid chromatography-mass spectrometry (LC-MS). These metabolomics profiles were analyzed by chemometric tools and the outcome was further validated using proteomic data from a separate sample cohort.

Results: The obtained metabolite patterns significantly differed between PC and benign tissue and between samples with high and low Gleason score (GS). Five key metabolites (phosphocholine, glutamate, hypoxanthine, arginine and alpha-glucose) were identified, who were sufficient to differentiate between cancer and benign tissue and between high to low GS. In ERG-positive PC, the analysis revealed several acylcarnitines among the increased metabolites together with decreased levels of proteins involved in beta-oxidation; indicating decreased acyl-CoAs oxidation in ERG-positive tumors. The ERG-positive group also showed increased levels of metabolites and proteins involved in purine catabolism; a potential sign of increased DNA damage and oxidative stress.

Conclusions: Our comprehensive metabolomic analysis strongly indicates that ERG-positive PC and ERG-negative PC should be considered as different subtypes of PC; a fact requiring different, sub-type specific treatment strategies for affected patients.

Background Survival from colorectal cancer has been shown to be lower in Denmark and England than in comparable high-income countries. We used data from national colorectal cancer registries to assess whether differences in the proportion of patients receiving resectional surgery could contribute to international differences in colorectal cancer survival. Methods In this population-based study, we collected data from all patients aged 18-99 years diagnosed with primary, invasive, colorectal adenocarcinoma from Jan 1, 2010, to Dec 31, 2012, in Denmark, England, Norway, and Sweden, from national colorectal cancer registries. We estimated age-standardised net survival using multivariable modelling, and we compared the proportion of patients receiving resectional surgery by stage and age. We used logistic regression to predict the resectional surgery status patients would have had if they had been treated as in the best performing country, given their individual characteristics. Findings We extracted registry data for 139457 adult patients with invasive colorectal adenocarcinoma: 12958 patients in Denmark, 97466 in England, 11450 in Norway, and 17583 in Sweden. 3-year colon cancer survival was lower in England (63.9%, 95% CI 63.5-64.3) and Denmark (65.7%, 64.7-66.8) than in Norway (69.5%, 68.4-70.5) and Sweden (72.1%, 71.2-73.0). Rectal cancer survival was lower in England (69.7%, 69.1-70.3) than in the other three countries (Denmark 72.5%, 71.1-74.0; Sweden 74.1%, 72.7-75.4; and Norway 75.0%, 73.1-76.8). We found no significant differences in survival for patients with stage I disease in any of the four countries. 3-year survival after stage II or III rectal cancer and stage IV colon cancer was consistently lower in England (stage II rectal cancer 86.4%, 95% CI 85.0-87.6; stage III rectal cancer 75.5%, 74.2-76.7; and stage IV colon cancer 20.5%, 19.9-21.1) than in Norway (94.1%, 91.5-96.0; 83.4%, 80.1-86.1; and 33.0%, 31.0-35.1) and Sweden (92.9%, 90.8-94.6; 80.6%, 78.2-82.7; and 23.7%, 22.0-25.3). 3-year survival after stage II rectal cancer and stage IV colon cancer was also lower in England than in Denmark (stage II rectal cancer 91.2%, 88.8-93.1; and stage IV colon cancer 23.5%, 21.9-25.1). The total proportion of patients treated with resectional surgery ranged from 47803 (68.4%) of 69867 patients in England to 9582 (81.3%) of 11786 in Sweden for colon cancer, and from 16544 (59.9%) of 27599 in England to 4106 (70.8%) of 5797 in Sweden for rectal cancer. This range was widest for patients older than 75 years (colon cancer 19078 [59.7%] of 31946 patients in England to 4429 [80.9%] of 5474 in Sweden; rectal cancer 4663 [45.7%] of 10195 in England to 1342 [61.9%] of 2169 in Sweden), and the proportion of patients treated with resectional surgery was consistently lowest in England. The age gradient of the decline in the proportion of patients treated with resectional surgery was steeper in England than in the other three countries in all stage categories. In the hypothetical scenario where all patients were treated as in Sweden, given their age, sex, and disease stage, the largest increase in resectional surgery would be for patients with stage III rectal cancer in England (increasing from 70.3% to 88.2%). Interpretation Survival from colon cancer and rectal cancer in England and colon cancer in Denmark was lower than in Norway and Sweden. Survival paralleled the relative provision of resectional surgery in these countries. Differences in patient selection for surgery, especially in patients older than 75 years or individuals with advanced disease, might partly explain these differences in international colorectal cancer survival. Copyright 2018 (C) The Author(s). Published by Elsevier Ltd.

Background and purpose: Trials in rectal cancer have shown that radiotherapy (RT) decreases local recurrence rates, whereas the effects on survival are uncertain. Swedish and Norwegian oncologists have had different treatment recommendations. The aim was to evaluate local recurrence rates and survival in the two countries.

Patients and methods: Between 1995 and 2012 rectal cancer patients registered in Sweden and Norway were analyzed, presenting population-based “real world” data.

Results: Totally 29,029 Swedish and 15,456 Norwegian patients were analyzed. Resection for cure was performed in two-thirds of the patients. RT was given to 49% of Swedish patients, mainly short-course RT and to 26% of Norwegian patients, predominantly chemoradiotherapy (CRT). In Sweden, the proportion irradiated was stable whereas in Norway, an increase from 10% to 40% was seen. Local 5-year recurrence rates were initially higher in Norway (12%) than in Sweden (8%), whereas they were equally low (4%) during the latter time. No survival differences were seen, however, survival improved with time in both countries.

Conclusions: Two entirely different approaches to preoperative therapy resulted in similar survival with initially higher local recurrence rates in Norway, but similarly low rates in later years. This raises questions about optimal RT rates and regimens.