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Objective: To estimate risk of prostate-specific antigen (PSA) relapse after radical radiotherapy (RT) for prostate cancer (PCa), and risk of PCa death after relapse according to Gleason score and time to relapse.

Patients and Methods: Men in the National Prostate Cancer Register of Sweden who underwent primary radical RT in 2007–2024 were followed until 31 December 2024. Relapse was defined as a PSA level increase of ≥2 ng/mL above nadir (Phoenix criteria). Competing risk cumulative incidence analyses were used to estimate risk of PSA relapse and risk of PCa death after relapse according to Gleason score and time to relapse.

Results: The 10-year risk of relapse in 26 634 men treated with RT was 25% (95% confidence interval [CI] 24–25%). The 10-year risk of PCa death after relapse was 35% (95% CI 33–37%). In men with relapse after >3 years the risk was 18% for Gleason score 6 and 19% for Gleason score 3 + 4, while in men with a relapse within 18 months the risk was 52% for Gleason score 4 + 3 and 75% for Gleason score 9–10. In men with a relapse at 1 year after RT there was a four-fold higher risk of PCa death for men with Gleason score 9–10 compared to men with Gleason score 6 (86% vs 22%). In contrast, in men with a relapse at 10 years after RT there were little differences in risk of PCa death according to Gleason (14% vs 23%).

Conclusion: In this population-based study of RT for PCa, there was a wide range in the estimates of risk of PCa death after relapse in highly granular groups according to Gleason score and time to relapse. Notably, some estimates did not align with the European Association of Urology relapse risk group classification.

BACKGROUND: Metastasis-directed stereotactic body radiotherapy (MD-SBRT) has shown promise in retrospective and phase II studies for oligometastatic hormone-sensitive prostate cancer. However, prospective randomized phase III data-particularly in newly diagnosed cases and in combination with androgen deprivation therapy and next-generation androgen receptor pathway inhibitors-are limited. The METRO trial investigates the addition of MD-SBRT to standard of care in patients with prostate-specific membrane antigen (PSMA) PET/CT-detected oligometastatic disease.

METHODS: METRO is a multicentre, double arm, open-label, phase III randomized trial comparing MD-SBRT plus standard of care versus standard of care alone in patients with one to three PSMA PET/CT-detected distant metastases. The PSMA-RADS scale is used to support inclusion, and only patients with PSMA-RADS 4 or 5 lesions in bone or non-regional lymph nodes are eligible.

Standard of care includes time-limited androgen deprivation therapy and/or androgen receptor pathway inhibitor, as well as local radiotherapy to the prostate or prostate bed. Patients are stratified by disease type (synchronous or metachronous) and metastasis location (lymph node/bone). The primary endpoint is biochemical progression-free survival; secondary endpoints include time to castration-resistant prostate cancer, adverse events, and health-related quality of life.

The intervention is prescribed either 30 Gy in 3 fractions or 40 Gy in 5 fractions and delivered by stereotactic treatment principles.

DISCUSSION: The METRO trial investigates the added value of combining MD-SBRT with time-limited intensified hormonal therapy in both synchronous and metachronous oligometastatic hormone-sensitive prostate cancer staged by PSMA‑PET/CT. The use of the PSMA-RADS scale for inclusion ensures a standardized and reproducible approach for patient selection.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04983095.

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.

OBJECTIVE: This article presents a summary of the 2025 Swedish prostate cancer guidelines, focusing on recurrence after local treatment, metastatic disease, and castration-resistant prostate cancer.

RESULTS: The 2025 Swedish guidelines introduce several important updates. Prostate specific membrane antigen (PSMA)-PET/CT is recommended only when PSA exceeds 0.2 µg/L, and reporting should follow the defined PSMA-RADS-scale. PSMA-PET/CT is preferred over lymph-node dissection for staging. A strong recommendation is issued for radiotherapy to the primary tumour in all oligometastatic men with a life expectancy > 5 years, whereas metastasis-directed therapy is restricted to clinical trials. Systemic treatment pathways now prioritise androgen receptor pathway inhibitors (ARPI) plus androgen deprivation therapy (ADT), with triple therapy (including docetaxel) used more selectively. Pathway-specific staging algorithms have been revised. The oly (ADP-ribose) polymerase inhibitor (PARPi) section has expanded, with broader genomic-based selection and integration into treatment sequencing. Two new chapters and an appendix address cardiovascular risk assessment before ARPI or chemotherapy. Supportive care is substantially strengthened.

Compared with the EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer 2025, the Swedish guidelines 2025 applies PSMA-PET/CT more conservatively, restricts PSMA-guided nodal salvage therapy, and issues a more universal recommendation for local radiotherapy in oligometastatic disease. The Swedish guidelines 2025 prioritise ARPI + ADT and limit triple therapy and PARPi combinations due to regulatory and reimbursement constraints. PARPi are largely reserved for BRCA1/2-mutated disease. The Swedish guidelines 2025 provide a more comprehensive framework for rehabilitation and survivorship.

CONCLUSIONS: The 2025 Swedish prostate cancer guidelines introduce multiple new recommendations and differ in several aspects from the European guidelines.

Background: HYPO-RT-PC is a phase 3 trial comparing ultra-hypofractionated and conventionally fractionated radiotherapy in intermediate-to-high-risk localised prostate cancer. This 10-year update reports long-term efficacy and toxicity outcomes.

Methods: In this open-label, randomised, phase 3, non-inferiority trial done in ten centres in Sweden and two in Denmark, we recruited men aged 75 years or younger with intermediate-risk or high-risk prostate cancer and a WHO performance status between 0 and 2. Previous or current androgen deprivation therapy was not permitted. Patients were randomly assigned (1:1) to ultra-hypofractionated radiotherapy (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventionally fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). Randomisation was performed with a minimisation algorithm balancing T stage, Gleason score, prostate-specific antigen, and trial centre. The primary endpoint was failure-free survival, defined as time from randomisation to the first occurrence of biochemical failure, evidence of clinical progression, initiation of androgen deprivation therapy, or death from prostate cancer, analysed in the per-protocol population. The non-inferiority margin was 4% at 5 years and had previously been met, corresponding to a critical hazard ratio (HR) limit of 1·338. Toxicity was assessed using the Radiation Therapy Oncology Group morbidity scale. Here, we report long-term efficacy and safety results at 10 years. The trial is registered with the ISRCTN registry, ISRCTN45905321, and is closed.

Findings: Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionated radiotherapy (n=602) or ultra-hypofractionated radiotherapy (n=598). Ten patients withdrew consent, eight were found to be ineligible, and two died of reasons unrelated to prostate cancer. 1180 patients constituted the per-protocol population (591 in the conventional fractionation group and 589 in the ultra-hypofractionation group). After a median follow-up of 10·6 years (IQR 9·0–13·0) in the conventional fractionation group and 10·7 years (9·1–12·7) in the ultra-hypofractionation group, 205 and 178 primary events were observed, respectively. 10-year failure-free survival was 65% (95% CI 61–69) in the conventionally fractionated group and 72% (68–76) in the ultra-hypofractionated group. The adjusted HR for the primary endpoint was 0·84 (95% CI 0·69–1·03; Cox regression analysis), confirming non-inferiority. The 10-year cumulative incidence of late grade 2 or worse genitourinary toxic effects was 30% (95% CI 26–34) in the conventional fractionation group and 28% (24–32) in the ultra-hypofractionated group (HR 1·01, 95% CI 0·81–1·25; p=0·95). For late grade 2 or worse gastrointestinal toxic effects, the corresponding figures were 14% (95% CI 11–18) and 14% (11–17; HR 0·94, 95% CI 0·70–1·28; p=0·72).

Interpretation: This 10-year follow-up confirms the non-inferiority of the ultra-hypofractionated radiotherapy regimen compared with the conventionally fractionated, with similar toxicity profiles. The findings support the seven-fraction schedule as a safe, effective, and practical standard-of-care option for patients with intermediate-risk prostate cancer.

Funding: The Nordic Cancer Union, the Swedish Cancer Society, the Swedish Research Council, the Swedish Prostate Cancer Association, and Cancerforskningsfonden i Norrland.

Objective: To describe the risk of urinary tract events after radical radiotherapy (RT) according to pre-RT (IPSS) overall and within subgroups of prostate volume, type of RT, and use of neoadjuvant androgen-deprivation therapy (ADT), as men who undergo RT for prostate cancer have a risk of urinary tract events.

Patients and Methods: Men in the National Prostate Cancer Register of Sweden who underwent RT between 2018 and 2023 for whom IPSS was registered at diagnosis were included. The IPSS was stratified as: low, 0–7; moderate, 8–19; and severe, 20–35 points. Urinary tract events were defined as lower urinary tract symptoms, infections, and urological procedures after treatment and assessed based on International Classification of Diseases and Related Health Problems, 10th Revision codes and procedures in The Patient Register. Competing risk of cumulative incidence proportion of urinary tract events at 3 year after RT was computed according to the IPSS, prostate volume, type of RT, and use of neoadjuvant ADT.

Results: Of the 4436 men included, 43% had mild, 44% moderate, and 13% severe pre-RT IPSS. Incidence of urinary tract events after RT was 19% at 3 years for men with mild IPSS, 28% for moderate IPSS, and 39% for severe IPSS. The association between IPSS and urinary tract events was observed within subgroups based on prostate volume, type of RT, and use of neoadjuvant ADT. A 5-unit increase in IPSS carried a 20% increased risk of having a urinary tract event within 3 years.

Conclusion: A higher pre-RT IPSS is an indicator of increased risk of urinary tract events after RT – both overall and within subgroups of prostate volume, type of RT, and use of neoadjuvant ADT.

The SPCG-13 trial investigated whether six cycles of adjuvant docetaxel (aDoc) improves survival in patients with intermediate- or high-risk prostate cancer after radical curative radiotherapy and androgen deprivation therapy. There was no difference in biochemical recurrence-free survival (primary endpoint) at 5-yr between the surveillance (SV) and aDoc arms. Here we report 10-yr survival data (planned secondary endpoint). Updated overall survival (OS) and metastasis-free survival data were available for 233 patients. There were no demographic differences between the original randomized cohort and the 10-yr survival population. Thus, this 10-yr sample is deemed representative of the original patient population. Median OS was 14.5 yr in the SV and was not reached in the aDoc arm. No significant difference in Kaplan-Meier survival emerged between the arms over time (log-rank test p = 0.154). Estimates of the 10-yr OS rate favored aDoc (77.4% vs 66.8%). Cox regression analysis revealed a trend towards worse OS for patients with a high Gleason score (GS; hazard ratio [HR] 1.925, 95% confidence interval [CI] 1.213-3.053; p = 0.005). A Cox model adjusted for GS risk revealed an OS HR of 0.776 (95% CI 0.508-1.187; p = 0.242) for aDoc versus SV. In conclusion, aDoc was associated with a slight, but not statistically significant, improvement in 10-yr OS, especially in the high-GS group.

PATIENT SUMMARY: Our 10-year survival analysis for the SPCG-13 trial showed that six cycles of chemotherapy with docetaxel after radiotherapy and androgen deprivation therapy for intermediate- or high-risk localized prostate cancer did not significantly increase survival. Survival was worse for cancers with a high Gleason score, so docetaxel could be considered after a careful discussion of the benefits and harms of chemotherapy. Further trials are needed to investigate options for this group of patients.

Background: Accurate diagnosis and staging are essential for optimal treatment planning of prostate cancer. By combining functional and anatomical imaging, PSMA-PET/mpMRI offers a potential to improve lesion detection and enhance staging accuracy. This study aimed to evaluate the diagnostic performance of lesion detection and local staging of prostate cancer using combined PSMA-PET/mpMRI compared to standalone mpMRI or PSMA-PET.

Results: Fifty-five patients with intermediate- to high-risk prostate cancer scheduled for robot-assisted laparoscopic radical prostatectomy were included. All patients underwent [68Ga]PSMA-PET/mpMRI prior to surgery. Whole-mount histopathology and surgical report served as reference standard. Two radiologists independently evaluated mpMRI, while two nuclear medicine physicians assessed PSMA-PET. For the PSMA-PET/mpMRI analysis, a consensus evaluation was performed by a new set of readers in two teams, each comprising one radiologist and one nuclear medicine physician. Lesion localization was reported based on the PI-RADS v2.1 sector map and compared to histopathology. Among 130 histopathologically confirmed lesions, mean detection rates were 38% (49.5/130) for PSMA-PET/mpMRI, 32% (41/130) for mpMRI and 32% (41/130) for PSMA-PET. For clinically significant prostate cancer (csPC) (≥0.5 ml, ≥ISUP 2; 42 lesions), mean detection rates were 85% (35.5/42) for PSMA-PET/mpMRI, 75% (31.5/42) for mpMRI and 70% (29.5/42) for PSMA-PET. The mean false discovery rates were 8% (PSMA-PET/mpMRI), 15% (mpMRI) and 12% (PSMA-PET). The likelihood of extraprostatic extension (EPE) and seminal vesicle invasion (SVI) were scored using a 5-point Likert scale, where scores of 1–3 were classified as negative and scores of 4–5 were considered positive. Sensitivity for EPE was 32% for PSMA-PET/mpMRI, 37% for mpMRI and 7% for PSMA-PET, with a specificity of 100%, 96% and 98%, respectively. For SVI, sensitivity was 50% for PSMA-PET/mpMRI and 38% for mpMRI and PSMA-PET, with a specificity of 100%, 95% and 97% respectively.

Conclusions: PSMA-PET/mpMRI provided higher and a more consistent performance in localized prostate cancer detection and staging without increasing false-positive findings.

Background and objective: Innovations have improved outcomes in advanced prostate cancer (PC). Nonetheless, we continue to lack high-level evidence on a variety of topics that greatly impact daily practice. The 2024 Advanced Prostate Cancer Consensus Conference (APCCC) surveyed experts on key questions in clinical management in order to supplement evidence-based guidelines. Here we present voting results for questions from APCCC 2024.

Methods: Before the conference, a panel of 120 international PC experts used a modified Delphi process to develop 183 multiple-choice consensus questions on eight different topics. Before the conference, these questions were administered via a web-based survey to the voting panel members (“panellists”).

Key findings and limitations: Consensus was a priori defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. The voting results show varying degrees of consensus, as discussed in this article and detailed in the Supplementary material. These findings do not include a formal literature review or meta-analysis.

Conclusions and clinical implications: The voting results can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers in prioritising areas for future research. Diagnostic and treatment decisions should always be individualised on the basis of patient and cancer characteristics, and should incorporate current and emerging clinical evidence, guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2024 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials.

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.