Pretreatment Patient-reported Overall Health: A Prognostic Factor for Early Overall Mortality After Primary Curative Treatment of Prostate Cancer.

Background and objective: Registry-based studies for prostate cancer (PCa) document higher overall mortality (OM) after high-dose radiotherapy (RT) than after radical prostatectomy (RP). Our aim was to explore the association between pretreatment patient-reported health ("OverallHealth": OH) and curative treatment type, and the impact on early OM. Methods: New PCa patients registered between 2017 and 2019 in the Cancer Registry of Norway (n = 1949) completed the European Organisation for Research and Treatment of Cancer Quality-of-Life Core 30 (QLQ-C30) questionnaire before RP (n = 592) or RT (n = 610) or after allocation to active surveillance (AS; n = 747). We dichotomised the QLQ-C30 summary score to classify patients with un-impaired versus impaired OH. Standard univariable and multivariable analyses with treatment type or OM as the outcome were conducted. The mean observation time was 4.7 years (standard deviation 1.0). Statistical significance was set at p < 0.05. Key findings and limitations: Impaired OH was more frequent in the RT group (38%) than in the RP (25%) or AS (28%) group (p < 0.001). Higher age, higher risk group, and impaired OH increased the probability of undergoinRT rather than RP (p < 0.001). Impaired OH was associated with a twofold higher early OM rate in the RT group (16% vs 8%; p = 0.009) and fourfold higher OM rate in the AS group (13% vs 3%; p < 0.001). These findings remained significant in Cox regression analyses controlled for age and risk group. After RP, only locally advanced high-risk tumours were significantly associated with OM. Unknown psychometrics for the OH variable is the main study limitation. Conclusions and clinical implications: Pretreatment patient-reported impaired OH, measured as the QLQ-C30 summary score, was positively associated with allocation to RT or AS and is a prognostic factor for early OM. Before allocation to RT or AS, elderly patients with PCa should be screened and treated for health problems that can be remedied. Future studies should determine the psychometrics of the QLQ-C30 summary score in comparison to established frailty screening instruments. Patient summary: Patient-reported scores reflecting their overall health can help in choosing curative treatment for prostate cancer and are associated with survival during the first 5 years after treatment.

Protocol of a randomised, controlled trial comparing immediate curative therapy with conservative treatment in men aged ≥75 years with non-metastatic high-risk prostate cancer (SPCG 19/GRand-P).

BACKGROUND: Older men (aged ≥75 years) with high risk, non-metastatic prostate cancer (PCa) are increasingly treated with curative therapy (surgery or radiotherapy). However, it is unclear if curative therapy prolongs life and improves health-related quality of life (HRQoL) in this age group compared to conservative therapy, which has evolved considerably during the last decade. STUDY DESIGN: The Scandinavian Prostate Cancer Group (SPCG) 19/Norwegian Get-Randomized Research Group-Prostate (GRand-P) is a randomised, two-armed, controlled, multicentre, phase III trial carried out at study centres in Norway, Denmark, Finland, and Sweden. ENDPOINTS: The primary endpoints are overall survival and HRQoL (burden of disease scale, European Organisation for the Research and Treatment of Cancer [EORTC] Elderly Cancer patients). Secondary endpoints are PCa-specific survival, metastasis-free survival, role-functioning scale (EORTC quality of life questionnaire 30-item core), urinary irritative/obstructive scale (26-item Expanded Prostate Cancer Index Composite [EPIC-26]), bowel scale (EPIC-26), intervention-free survival, PCa morbidity, use of secondary and tertiary systemic therapies, mean quality-adjusted life-years (QALYs), and mean total healthcare costs. PATIENTS AND METHODS: A total of 980 men (aged ≥75 years) with non-metastatic, high-risk PCa will initially be screened with Geriatric 8 (G8) health status screening tool and Mini-COG© brief cognitive test. Participants identified by G8 as 'fit' or 'frail' will be randomised (ratio 1:1) to either immediate curative therapy (radiotherapy or prostatectomy) or conservative therapy (endocrine therapy or observation). Participants who are unable or unwilling to participate in randomisation will be enrolled in a separate observation group. Randomised patients will be followed for 10 years. TRIAL REGISTRATION: Ethics approval has been granted in Norway (457593), Denmark (H-22051998), Finland (R23043) and Sweden (Dnr 2023-05296-01). The trial is registered on Clinicaltrials.org (NCT05448547).

Do all prostate cancer patients want, and experience shared decision making prior to curative treatment?

OBJECTIVE: In comparable men with non-metastatic prostate cancer, radical prostatectomy (RP), radiotherapy (RAD) and active surveillance (AS) are treatment options with similar survival rates, but different side-effects. Healthcare professionals consider pretreatment shared decision making (SDM) to be an essential part of medical care, though the patients' view about SDM is less known. In this article, we explore prostate cancer (PCa) patients' SDM wish (SDMwish), and experiences (SDMexp).  Material and methods: This is a registry-based survey performed by the Cancer Registry of Norway (2017-2019). One year after diagnosis, 5,063 curatively treated PCa patients responded to questions about their pre-treatment wish and experience regarding SDM. Multivariable analyses identified factors associated with SDM. Statistical significance level: p < 0.05.  Results: Overall, 78% of the patients wished to be involved in SDM and 83% of these had experienced SDM. SDMwish and SDMexp was significantly associated with decreasing age, increasing education, and living with a partner. Compared with the RP group, the probability of SDMwish and SDMexp was reduced by about 40% in the RAD and the AS groups.  Conclusion: Three of four curatively treated PCa wanted to participate in SDM, and this wish was met in four of five men. Younger PCa patients with higher education in a relationship, and opting for RP, wanted an active role in SDM, and experienced being involved. Effective SDM requires the responsible physicians' attention to the individual patients' characteristics and needs.

Long-term patient follow-up should be routinely implemented in radiotherapy units to detect late adverse effects after cancer treatment.

Editorial comment to Urosymphyseal fistula after pelvic radiotherapy - an entity in patients with significant comorbidity requiring multidisciplinary management Scand J Urol. 2023.

Baseline Serum Prostate-specific Antigen Value Predicts the Risk of Subsequent Prostate Cancer Death-Results from the Norwegian Prostate Cancer Consortium.

BACKGROUND: Prostate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality. OBJECTIVE: To determine the association between midlife PSA levels <4.0 ng/ml, drawn as part of routine medical care, and long-term risk of prostate cancer death. DESIGN, SETTING, AND PARTICIPANTS: The Norwegian Prostate Cancer Consortium collected >8 million PSA results from >1 million Norwegian males ≥40 yr of age. We studied 176 099 men (predefined age strata: 40-54 and 55-69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1, 1995 and December 31, 2005. INTERVENTION: Baseline PSA. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5-0.9, 1.0-1.9, 2.0-2.9, and 3.0-3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method. RESULTS AND LIMITATIONS: The median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0-3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40-54 and 55-69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation. CONCLUSIONS: We replicated prior studies that baseline PSA at age 40-69 yr can be used to stratify a man's risk of dying from prostate cancer within the next 15-20 yr. PATIENT SUMMARY: A prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man's risk of dying from prostate cancer in the next two decades.

Impact of prebiopsy MRI on prostate cancer staging: Results from the Norwegian Prostate Cancer Registry.

Objectives: The aim of this study is to evaluate the 2015 introduction of prebiopsy magnetic resonance imaging of the prostate (MRI-P) as the standard of care for diagnosing prostate cancer (PCa) by the Norwegian public health care authorities. There were three specific objectives of this study: first, to evaluate the consequences of using different TNM manuals for clinical T-staging (cT-staging) in a national setting; second, to determine if the data reveals that MRI-P based cT-staging is superior to digital rectal examination (DRE)-based cT-staging compared with pathological T-stage (pT-stage) post radical prostatectomy; and third, to assess whether treatment allocations have changed over time. Materials and Methods: All patients registered in the Norwegian Prostate Cancer Registry between 2004 and 2021 were retrieved and 5538 were eligible for inclusion. Concordance between clinical T-stage (cT-stage) and pT-stage was assessed by percentage agreement, Cohen's kappa and Gwet's agreement. Results: MR visualisation of lesions influences reporting of tumour extension beyond DRE findings. Agreement between cT-stage and pT-stage declined from 2004 to 2009, which coincided with an increase in the percentage being pT3. From 2010, agreement increased, which aligned with changes in cT-staging and the introduction of MRI-P. From 2017, regarding the reporting of cT-DRE and cT-Total (overall cT-stage), agreement diminished for cT-DRE but remained relatively stable (>60%) for cT-Total. Regarding treatment allocation, the study suggests that staging with MRI-P has shifted treatment towards radiotherapy in locally advanced high-risk disease. Conclusion: Introduction of MRI-P has affected cT-stage reporting. Agreement between cT-stage and pT-stage appears to have improved. This study suggests that use of MRI-P influences treatment decisions in certain patient subgroups.

The Changing Face of cN0M0 Prostate Cancer Being Found With pN+ After Surgery in the Contemporary Era: Results of an International European Survey on Disease Management.

INTRODUCTION: The urological community's opinion over the management of men being found with pathologically positive nodes (pN+) following radical prostatectomy (RP) performed with curative intent after preoperative negative conventional staging (cN0M0) has never been assessed. This remains crucial, especially considering the advent of novel imaging modalities. Our aim was to investigate the current opinion on management of pN+ cN0M0 prostate cancer (PCa) in the European urological community. METHODS: Following validation, a 31-item survey, complying with the Cherries checklist, was distributed using a web link from December 2021 to April 2022 to 10 urological societies mailing list. Social media (Twitter, Facebook) were also used. RESULTS: We received 253 replies. The majority were Urologists (96.8%), younger than 60 (90.5%); 5.2% did not have access to PET-scans; 78.9% believed pN+ is a multifaceted category; 10-years CSS was marked as 71 to 95% by 17.5%. Gold standard management was stated not being ADT by 80.8% and being RT±ADT by 52.3%. Early sRT±ADT was considered an option vs. aRT±ADT by 72.4%. In case of BCR 71% would perform and decide management based on PSMA-PET whilst 3.7% would not perform PSMA-PET. pN+ management is still unclear for 77.1%. On multivariate analysis PSMA-PET availability related to a lower and higher likelihood of considering aRT±ADT as standard and of considering early salvage versus aRT respectively (P < .05). CONCLUSIONS: The Urological community has an acceptable awareness of pN+ disease and management, although it may overestimate disease aggressiveness. The majority consider pN+ PCa as a multifaceted category and rely on a risk-adapted approach. Expectant compared to immediate upfront management and new imaging modalities are increasingly considered.

Comparative Survival Outcomes of High-risk Prostate Cancer Treated with Radical Prostatectomy or Definitive Radiotherapy Regimens.

BACKGROUND: Observational data has indicated improved survival after radical prostatectomy (RP) compared with definitive radiotherapy (RT) in men with high-risk prostate cancer (PCa). OBJECTIVE: To compare PCa-specific mortality (PCSM) and overall mortality (OM) in men with high-risk PCa treated with RP or RT, providing information on target doses and fractionations. DESIGN SETTING AND PARTICIPANTS: This is an observational study from the Cancer Registry of Norway. Patients were diagnosed with high-risk PCa during 2006-2015, treated with RP ≤12 mo or RT ≤15 mo after diagnosis, and stratified according to RP or RT modality; external beam radiotherapy (EBRT; 70-<74, 74-<78, or 78 Gy), hypofractionated RT or EBRT combined with brachytherapy (BT-RT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Competing risk and Kaplan-Meier methods estimated PCSM and OM, respectively. Multivariable Cox regression models evaluated hazard ratios (HRs) for PCSM and OM. RESULTS AND LIMITATIONS: In total, 9254 patients were included (RP 47%, RT 53%). RT patients were older, had poorer performance status and more unfavorable disease characteristics. With a median follow-up time of seven and eight yrs, the overall 10-yr PCSM was 7.2% (95% confidence interval [CI] 6.4-8.0) and OM was 22.9% (95% CI 21.8-24.1). Compared with RP, EBRT 70-<74 Gy was associated with increased (HR 1.88, 95% CI 1.33-2.65, p < 0.001) and BT-RT with decreased (HR 0.49, 95% CI 0.24-0.96, p = 0.039) 10-yr PCSM. Patients treated with EBRT 70-78 Gy had higher adjusted 10-yr OM than those treated with RP. CONCLUSIONS: In men with high-risk PCa, treatment with EBRT <74 Gy was associated with increased adjusted 10-yr PCSM and OM, and BT-RT with decreased 10-yr PCSM, compared with RP. PATIENT SUMMARY: In this study, we compared mortality after radical prostatectomy (RP) and radiotherapy (RT) in men with high-risk prostate cancer (PCa); the results suggest that men receiving lower-dose RT have higher, and patients receiving brachytherapy may have lower, risk of death from PCa than patients treated with prostatectomy.

Definitive radiotherapy for prostate cancer in Norway 2006-2015: Temporal trends, performance and survival.

BACKGROUND: More studies are needed to document nation-wide use and effectiveness of curative definitive radiotherapy (Def-RT) in the treatment of prostate cancer (PCa). PATIENTS AND METHODS: For 38,960 men diagnosed with PCa without distant metastases from 2006 to 2015 data from the Norwegian Prostate Cancer Registry and a national radiotherapy database (NoRadBase) was analyzed. Overall survival and PCa-specific mortality were described comparing EQD-2 < 74 Gy ("low-dose") with EQD-2 ≥ 74 Gy ("escalated dose"). RESULTS: Use of Def-RT decreased (27-24%) whereas the proportion of radical prostatectomies (RPs) increased (31-38%). In high-risk patients the use of RP doubled (18-36%), while the proportion of Def-RT remained stable (about 35%). Before 2010, almost a quarter of patients received low-dose Def-RT with gradual increase of escalated Def-RT thereafter. Escalated Def-RT was associated with significantly more favorable 10-year PCa-specific mortality (4.4% [95% CI: 2.7-10.7%]) than observed after low-dose Def- RT (8.8% [95% CI: 6.2-9.8%), with the most beneficial effects in high-risk patients. Our analyses indicated the need to expand the NoRadBase by consensus-based quality measures. CONCLUSION: In this nationwide cohort, the overall use of Def-RT decreased slightly. In high-risk patients the provision of Def-RT remained stable and was accompanied by doubling of patients with RP and reduction of a "no curative treatment" strategy. Escalated dose Def-RT significantly reduced 10-year PCa-specific mortality compared to low-dose Def-RT. Aiming for cancer care equity national radiotherapy registries for PCa should regularly monitor data based on consensus-based quality measures enabling feedback to the responsible hospitals.

Increased curative treatment is associated with decreased prostate cancer-specific and overall mortality in senior adults with high-risk prostate cancer; results from a national registry-based cohort study.

BACKGROUND: The association between curative treatment (CurTrt) and mortality in senior adults (≥70 years) with high-risk prostate cancer (PCa) is poorly documented. In a population-based cohort we report temporal trends in treatment and PCa-specific mortality (PCSM), investigating the association between CurTrt and mortality in senior adults with high-risk PCa, compared to findings in younger men (<70 years). METHODS: Observational study from the Cancer Registry of Norway. Patients with high-risk PCa were stratified for three diagnostic periods (2005-08, 2009-12 and 2013-16), age (<70, vs ≥70) and primary treatment (CurTrt: Radical prostatectomy (RP), Radiotherapy (RAD) vs no curative treatment (NoCurTrt)). Competing risk and Kaplan-Meier methods estimated PCSM and overall mortality (OM), respectively. Multivariable logistic regression models estimated odds for CurTrt, and multivariable Fine Gray and Cox regression models evaluated the hazard ratios for PCSM and OM. RESULTS: Of 19 763 evaluable patients, 54% were aged ≥70 years. Senior adults had more unfavorable PCa characteristics than younger men. Across diagnostic periods, use of CurTrt increased from 15% to 51% in men aged ≥70 and 65% to 81% in men aged < 70 years. With median five years follow-up, PCSM decreased in all patients (P < .05), in the third period restricted to senior adults. In all patients NoCurTrt was associated with three-fold higher 5-year PCSM and two-fold higher OM compared to CurTrt. CONCLUSIONS: In high-risk PCa patients, increased use of CurTrt, greatest in senior men, was observed along with decreased PCSM and OM in both senior and younger adults. CurTrt should increasingly be considered in men ≥70 years.

Improved patient-reported functional outcomes after nerve-sparing radical prostatectomy by using NeuroSAFE technique.

Purpose: To explore whether prostatectomized men report improved post-operative erectile function and urinary control dependent on the application of intra-operative frozen section examination (NeuroSAFE) during nerve-sparing radical prostatectomies (NS-RPs).Methods: Pre- and post-RP responses to the sexual domain and the urinary incontinence subscale of EPIC-26 were analyzed in 95 and 312 men from a NeuroSAFEGroup (Martini-Klinik, Hamburg, Germany) and a Non-NeuroSAFE Group (Oslo University Hospital, Norway), respectively, undergoing NS-RPs for ≤ cT2 prostate cancer. All patients had intra-prostatic tumors as evaluated by Digital Rectal Examination. Statistical significance in bivariate and multi-variable analyses: p < 0.05.Results: With similar oncological outcomes and not associated with the performance of bilateral or unilateral NS-RP within each group patients from the NeuroSAFE Group had better sexuality outcomes than those from the NonNeuroSAFE Group (p < 0.01). Age and pre-RP sexual function represented significant co-variables. In pre-RP potent men, erectile function was preserved in 74% of men in the NeuroSAFE Group and in 46% in those from the NonNeuroSAFE Group (p < 0.01). Any superior continence-saving effect of NeuroSAFE was limited. The non-randomized small-sized observational study design represents the observations' main limitation.Conclusions: Our study indicates that NeuroSAFE contributes to preservation of post-RP erectile function. If confirmed in a randomized trial the NeuroSAFE should be applied in patients undergoing NS-RP for maximal preservation of post-RP sexual function.

Impact of positive surgical margins on secondary treatment, palliative radiotherapy and prostate cancer-specific mortality. A population-based study of 13 198 patients.

BACKGROUND: The results of studies evaluating the impact of positive surgical margins on prostate cancer-specific mortality have been inconsistent. We, therefore, evaluated the impact of surgical margin status on subsequent secondary treatment, palliative radiotherapy, and prostate cancer-specific mortality. METHODS: A total of 14 837 men treated with radical prostatectomy (RP) during the period 2001 to 2015 were identified from the Cancer Registry of Norway. Of those, 13 198 (89%) patients had complete data on the preoperative prostate-specific antigen level, pathological T-category, Gleason score in the prostatectomy specimen, and margin status. Multivariable Cox proportional hazards models were used to evaluate the risk, and flexible parametric models for the cumulative incidence were fitted to predict the probabilities of secondary treatment (salvage radiotherapy or prophylactic breast radiation), palliative radiotherapy, and prostate cancer-specific mortality. RESULTS: After a median follow-up time of 5.2 years (3591 patients with ≥8 years of follow-up), positive surgical margins (PSMs) were independently predictive of secondary treatment (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 2.21-2.66) and palliative radiotherapy (HR = 1.45, 95% CI = 1.03-2.05). After 10 years, the absolute increased risk for palliative radiotherapy in patients with PSMs after RP varied between 0.1% in pT2 tumors with a Gleason score of 6, to 12% for pT3b tumors with a Gleason score of 9 to 10. PSMs were not independently associated with prostate cancer-specific mortality (HR = 1.14, 95% CI = 0.82-1.59). CONCLUSION: PSMs were associated with increased application of secondary treatment and palliative radiotherapy but were not predictive of prostate cancer-specific mortality. As the use of palliative radiotherapy was only marginally increased in patients with PSMs and the lowest-risk disease characteristics, avoiding PSMs may be of greatest prognostic relevance in patients with higher-risk disease characteristics.

Is time from diagnosis to radical prostatectomy associated with oncological outcomes?

PURPOSE: To study the association between time from diagnosis to radical prostatectomy (RP-interval) and prostate cancer-specific mortality (PCSM), histological findings in the RP-specimen and failure after RP (RP-failure). METHODS: Patients diagnosed with non-metastatic prostate cancer (PCa) in 2001-2010 and prostatectomized within 180 days of biopsy were identified in the Cancer Registry of Norway and the Norwegian Prostate Cancer Registry. Patients were stratified according to risk groups and RP-intervals of 0-60, 61-90, 91-120 and 121-180 days. Aalen-Johansen and Kaplan-Meier methods estimated curves for PCSM, RP-failure and overall mortality. Multivariable Cox regressions and Chi-square tests were used to evaluate the impact of RP-interval on outcomes. RESULTS: In 5163 eligible patients, the median time from diagnosis to RP was 93 days (range 1-180). Risk group distribution was similar in all RP-interval groups. With almost eight years of observation, no association was found between RP-interval and PCSM in the intermediate-or high-risk groups. Increasing RP-interval did not increase the rate of adverse histological outcomes or incidence of RP-failure. CONCLUSIONS: Increasing RP-interval up to 180 days was not associated with adverse oncological outcomes at eight years follow-up. These findings should be considered when planning for prostatectomy.

Ten-year Mortality in Men With Nonmetastatic Prostate Cancer in Norway.

OBJECTIVE: To provide population-based data on 10-year prostate cancer-specific mortality (PCSM), overall mortality (OM), treatment, and prognostic factors in patients with nonmetastatic prostate cancer (PCa). MATERIALS AND METHODS: Based on data from the Norwegian Prostate Cancer Registry, we calculated 10-year PCSM and OM in 3449 patients diagnosed with nonmetastatic PCa in 2004-2005 who underwent radical prostatectomy (n = 913), radiotherapy (n = 1334), or no local treatment (n = 1202). Patients were stratified according to risk group, Gleason grade group (GGG), and Eastern Cooperative Oncology Group (ECOG) performance status. Aalen-Johansen and Kaplan-Meier estimates and proportional hazards regressions were used. RESULTS: The 10-year PCSM rate was 8.5% (radical prostatectomy: 1.5, radiotherapy: 6.2%, no local treatment: 16.3%) and the OM rate was 25.5%. In the low-risk group, the risk of dying from other causes was 8-fold increased compared with death from PCa, the comparable factor being approximately 2 among high-risk patients. Patients with high-risk factors seemed to benefit the most from local treatment. Within each risk group, the 5 GGGs improved the prediction of PCSM. Having an ECOG performance status of ≥1 doubled the risk of PCSM compared with patients with an ECOG performance status of 0. CONCLUSION: For all patients, the 10-year OM was about 3 times higher than PCSM, the greatest and lowest discrepancies emerging among patients with low- and high-risk tumors, respectively. The results support increased use of local treatment in high-risk patients. GGGs should be implemented in clinical practice. The role of ECOG performance status as prognostic factor has to be validated in future studies.