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).

Multi-parametric MRI without artificial erection for preoperative assessment of primary penile carcinoma: A pilot study on the correlation between imaging and histopathological findings.

Purpose: We aimed to evaluate the diagnostic potential of non-erectile multi-parametric magnetic resonance imaging (mpMRI) for preoperative assessment of primary penile squamous cell carcinoma (SCC). Method: Twenty-five patients who underwent surgery for penile SCC were included. Preoperative mpMRI without artificial erection was performed in all patients. The preoperative MRI protocol consisted of high-resolution morphological and functional sequences (diffusion-weighted imaging and dynamic contrast-enhanced MRI perfusion) covering the penis and lower pelvis. T and N staging, according to the 8th edition of the Union for International Cancer Control TNM classification, as well as the largest diameter and thickness/infiltration depth of the primary lesions were determined in all patients. Imaging data were retrospectively collected and compared with the final histopathology reports. Results: Very good agreement was observed between MRI and histopathology for the involvement of corpus spongiosum (p = 0.002) and good agreement was observed for the involvement of penile urethra and tunica albuginea/corpus cavernosum (p < 0.001 and p = 0.007, respectively). Good agreement was observed between MRI and histopathology for overall T staging and weaker, but still good agreement was observed for N staging (p < 0.001 and p = 0.002, respectively). A strong and significant correlation was observed between MRI and histopathology for the largest diameter and thickness/infiltration depth of the primary lesions (p < 0.001). Conclusions: Good concordance was observed between MRI and histopathological findings. Our initial findings indicate that non-erectile mpMRI is useful in preoperative assessment of primary penile SCC.

Validating the screening criteria for bone metastases in treatment-naïve unfavorable intermediate and high-risk prostate cancer - the prevalence and location of bone- and lymph node metastases.

OBJECTIVE: The European Association of Urology (EAU) recommends a bone scan for newly diagnosed unfavorable intermediate- and high-risk prostate cancer. We aimed to validate the screening criteria for bone metastases in patients with treatment-naïve prostate cancer. METHODS: This single-center retrospective study included all patients with treatment-naïve unfavorable intermediate- or high-risk prostate cancer. All underwent MRI of the lumbar column (T2Dixon) and pelvis (3DT2w, DWI, and T2 Dixon). The presence and location of lymph node and bone metastases were registered according to risk groups and radiological (rad) T-stage. The risk of lymph node metastases was assessed by odds ratio (OR). RESULTS: We included 390 patients, of which 68% were high-risk and 32% were unfavorable intermediate-risk. In the high-risk group, the rate of regional- and non-regional lymph node metastases was 11% and 6%, respectively, and the rate of bone metastases was 10%. In the unfavorable intermediate-risk group, the rate of regional- and non-regional lymph node metastases was 4% and 0.8%, respectively, and the rate of bone metastases was 0.8%. Metastases occurred exclusively in the lumbar column in 0.5% of all patients, in the pelvis in 4%, and the pelvis and lumbar column in 3%. All patients with bone metastases had radT3-4, and patients with radT3-4 showed a four-fold increased risk of lymph node metastases (OR 4.48, 95% CI: 2.1-9.5). CONCLUSION: Bone metastases were found in 10% with high-risk prostate cancer and 0.8% with unfavorable intermediate-risk. Therefore, we question the recommendation to screen the unfavorable intermediate-risk group for bone metastases. KEY POINTS: • The rate of bone metastases was 10% in high-risk patients and 0.8% in the unfavorable intermediate-risk group. • The rate of lymph-node metastases was 17% in high-risk patients and 5% in the unfavorable intermediate-risk group. • No bone metastases were seen in radiologically localized disease.

Robotic salvage pelvic lymph node dissection for locoregional recurrence after radical prostatectomy: a single institution experience.

OBJECTIVES: To assess treatment response (PSA < 0.2 ng/ml), need for additional therapy and complication rate after robot assisted salvage pelvic lymph node dissection (sPLND). MATERIAL AND METHODS: Analysis of outcomes data from radical prostatectomy (RP) patients consecutively operated with robot assisted sPLND due to biochemical recurrence and positron-emission tomography (PET)/computed tomography (CT)-detected nodal recurrence of pelvic lymph nodes. RESULTS: Sixty-nine patients underwent robotic sPLND after a median time of 47 months post- RP. Sixty-four patients (93%) had malignant lymph nodes upon histological assessment of sPLND specimen. Twenty patients (29%) achieved PSA < 0.2 ng/ml 6 weeks postoperatively. After median (IQR) follow-up of 15 months (10-27), fourteen patients (20%) still had PSA < 0.2 ng/ml without additional therapy and forty-one patients (59%) had started additional therapy. No significant predictor for treatment response was found. Postoperative complications occurred in 14 patients (20%). Eleven of these complications were classified as Clavien-Dindo grade 1. CONCLUSION: Oncological benefit of sPLND as the only salvage procedure seems to be limited, though almost one third of patients achieved treatment response. Clinical trials are needed to determine if sPLND as part of a multimodal treatment may improve outcome.

The prevalence and locations of bone metastases using whole-body MRI in treatment-naïve intermediate- and high-risk prostate cancer.

OBJECTIVE: The aim of this study was to assess the prevalence and distribution of bone metastases in treatment-naïve prostate cancer patients eligible for a metastatic workup using whole-body MRI, and to evaluate the results in light of current guidelines. METHODS: This single-institution, retrospective study included all patients with treatment-naïve prostate cancer referred to whole-body MRI during 2016 and 2017. All were eligible for a metastatic workup according to the guidelines: PSA > 20 ng/ml and/or Gleason grade group ≥ 3 and/or cT ≥ 2c and/or bone symptoms. The definition of a metastasis was descriptive and based on the original MRI reports. The anatomical location of metastases was registered. RESULTS: We included 161 patients with newly diagnosed prostate cancer of which 36 (22%) were intermediate-risk and 125 (78%) were high-risk. The median age and PSA were 71 years (IQR 64-76) and 13 ng/ml (IQR 8-28), respectively. Bone metastases were found in 12 patients (7%, 95% CI: 4-13), and all were high-risk with Gleason grade group ≥ 4. The pelvis was affected in 4 patients, and the spine + pelvis in the remaining 8. No patients demonstrated metastases to the spine without concomitant metastases in the pelvis. Limitations are the small number of metastases and retrospective design. CONCLUSION: This study suggests that the overall prevalence of bone metastases using the current guidelines for screening is quite low. No metastases were seen in the case of Gleason grade group ≤ 3, and further studies should investigate if it necessary to screen non-high-risk patients. KEY POINTS: • The overall prevalence of bone metastases was 7% in the case of newly diagnosed intermediate- and high-risk prostate cancer. • The prevalence in high-risk patients was 10%, and no metastases were seen in patients with Gleason grade group ≤ 3. • The pelvic skeleton is the main site, and no metastases occurred in the spine without concomitant pelvic metastases.

Switching from laparoscopic radical prostatectomy to robot assisted laparoscopic prostatectomy: comparing oncological outcomes and complications.

OBJECTIVES: To compare oncological outcomes and complication rates based on the Clavien classification between laparoscopic radical prostatectomies (LRP) and robot-assisted laparoscopic radical prostatectomies (RALP). MATERIAL AND METHODS: In a prospective quality registry clinical data were consecutively entered for 544 LRP and 1081 RALP patients operated from 2003 to the end of 2012. Complications within 90 days postoperatively were assessed according to the Clavien classification and compared between LRP and RALP patients. Univariate and multivariate analyses of logistic regression were used to fit oncological outcomes and complication data. RESULTS: The mean operation time was 213 and 135 minutes in LRP and RALP patients, respectively. Pathological T3a stage (pT3a) in the RALP group was more frequent than in the LRP group, 32.4% versus 17.8%, respectively. For pT2 tumours, positive surgical margins (PSM) rate for LRP and RALP, was 20.3% vs 10.6%, respectively (p < .001). In the LRP group 74 patients (13.6%) reported 104 and in the RALP group 141 patients (13.0%) reported 177 complications (p = .75). Seventeen (3.1%) LRP patients and 15 (1.4%) RALP patients had Clavien grade IIIb complications (p = .017). Surgical reintervention was necessary in 14 patients (2.6%) and 17 patients (1.6%) in the LRP and RALP group, respectively (p = .04). CONCLUSION: Switching from LRP to RALP resulted in a much shorter operation time without compromising oncological outcome. There was no statistically significant difference in overall complication-rates between LRP and RALP. However, LRP patients had more serious complications and increased need for surgical reintervention compared to RALP patients.

Genetic variation in three species of Hordeum, and the selection of accessions for the Barley Core Collection.

Starch gel electrophoresis of isozymes was used to investigate the level and distribution of genetic variation in accessions of three wild, diploid Hordeum species. Allelic variation was assessed for seven isozyme loci and used in the statistical analysis of 18 accessions of Hordeum brachyantherum subsp. californicum, 29 accessions of H. murinum subsp. glaucum and 11 accessions of H. pusillum. A major purpose with this study was to evaluate the selection of accessions for the international Barley Core Collection, complementing existing passport data. Allelic variation was found in all three species. The variation was mainly between accessions, as most accessions were fixed for certain alleles. Since all three species are self-pollinated, this was anticipated. The fact that the accessions have undergone one or several regeneration cycles from a rather limited number of individuals, after being collected, likely also have reduced the variation. The accessions were clustered by subjecting the genetic distances between them to UPGMA statistical treatment. The clusters in the dendrograms displayed for H. brachyantherum subsp. californicum and H. pusillum distinct patterns related to the geographical origin of the accessions. The accessions of H. murinum subsp. glaucum were less variable than the other two, and did not reveal such a clear pattern. By comparing the already made, geographically based, selection of accessions with the results from this study, it was evident that the selection had worked fairly well for H. brachyantherum subsp. californicum, but less so for the other two species.