Mona Kafka

Objectives: To identify contemporary drivers of postoperative decision regret 1 year after radical prostatectomy (RP). Patients and Methods: In this prospective, multicentre study, patients undergoing robot‐assisted RP (RARP) or retropubic open RP (ORP) for localised prostate cancer at seven centres in Germany and Austria (2022–2024) completed questionnaires preoperatively and at 1 year postoperatively. Decision regret was assessed using the Decision Regret Scale (DRS). Functional outcomes were measured with European Organisation for Research and Treatment of Cancer quality of life questionnaire – 25‐item prostate cancer specific (EORTC QLQ‐PR25) symptom scores at 1 year postoperatively. Multivariable logistic regression identified predictors of high surgical decision regret (DRS score ≥10). Sensitivity was tested via propensity score matching (PSM). Results: A total of 419 patients completed the surveys (58% RARP, 42% ORP) at 1 year postoperatively. Surgical decision regret was low (mean [SD] DRS score 9.0 [15.4]). Erectile dysfunction was the outcome that most patients self‐reported as worse than expected (54% [221/404]), followed by urinary incontinence (23% [96/414]) and oncological cure (10% [39/397]) in a questionnaire on their retrospective perception. The ORP patients reported higher regret regarding surgical approach than RARP patients (mean [SD] DRS score 11.3 [17.1] vs 7.4 [13.9], P = 0.02). In a multivariate analysis, high urinary symptom burden (odds ratio [OR] 2.4, P = 0.009) and impaired sexual functioning (OR 2.8, P = 0.002) independently predicted high surgical decision regret whereas surgical approach and prostate‐specific antigen recurrence did not. Sensitivity analyses via PSM confirmed these independent predictors. Conclusions: Surgical decision regret after RP is primarily driven by postoperative functional outcomes rather than oncological results or surgical approach. Optimising functional recovery and managing patient expectations are key strategies to reduce regret in prostate cancer surgery.

Purpose: Active surveillance (AS) is the standard approach for managing ISUP 1 prostate cancer (PCa), ensuring oncological safety while minimizing overtreatment. However, AS protocols vary significantly. This study assessed a structured AS protocol incorporating PSA kinetics, multiparametric MRI (mpMRI), and targeted biopsies to identify predictors of treatment transition. Methods: We retrospectively reviewed 89 patients with ISUP 1 PCa managed with AS between 2010 and 2024. Inclusion criteria were PSA < 10 ng/mL and ≤ 2 positive biopsy cores with ≤ 50% tumor involvement per core. Patients underwent regular PSA testing, mpMRI, and risk-adapted biopsies. Outcomes included treatment conversion, progression predictors, and the role of mpMRI. Results: Median follow-up was 52.8 months. PSA was monitored at a median interval of 4.8 months, and mpMRI every 15.7 months (median). At diagnosis, 68.5% underwent mpMRI, with PIRADS 4 as the most frequent. During AS, 66.3% underwent at least one re-biopsy, most commonly triggered by PSA progression (73%). Treatment was initiated in 37.1% after a median of 37.9 months due to PSA progression (54.5%), mpMRI changes (21.2%), combined PSA/mpMRI findings (6.1%), histological upgrading (9.1%), or patient preference (3%). Treatments included radical prostatectomy, EBRT or LDR brachytherapy. Among these patients, no PSA persistence was observed; biochemical recurrence occurred in 6.1%, metastases in 4.0%, and overall mortality in 4.5%, with no PCa-specific deaths. Conclusion: A structured, risk-adapted AS protocol using PSA kinetics and mpMRI enabled personalized management and timely detection of progression. These findings support the standardization of AS protocols, which should be validated in larger cohorts.

Background/Objectives: Robot-assisted and open radical prostatectomy (RARP and ORP) are established procedures for localized prostate cancer, with comparable oncological and functional outcomes. Little is known about patients’ knowledge of both procedures. This study aimed to examine comparatively the informational behaviour and knowledge of patients undergoing ORP vs. RARP. Methods: This prospective, multicentre study included patients who underwent RARP or ORP prior to presurgery counselling. The questionnaires gathered information about patients’ information-seeking behaviours and their assessment of outcomes for RARP vs. ORP. We investigated risk factors for the misperception of procedure outcomes. Results: A total of 508 patients were included (307 RARP (60%); 201 ORP (40%)). The most common sources of information were outpatient urologists (84%), urologic departments (67%) and the internet (57%). Compared with ORP, RARP patients more often received the same amount of information about both procedures (60% vs. 40%, p < 0.001). Compared with ORP, RARP patients wrongfully considered their procedure to be superior in terms of oncological and functional outcomes. In the multivariable analysis, age > 66 years (OR 2.1, p = 0.02), no high school degree (OR 1.9, p = 0.04), unbalanced information search (OR 2.4, p = 0.02), RARP patient status (OR 8.9, p < 0.001), and treatment at a centre offering only one procedure (OR 3.5, p < 0.001) were independent predictors of misperception. Conclusions: RARP patients wrongfully considered their intervention to be oncologically and functionally more beneficial than ORP patients perceived it to be. This may be due to unbalanced sources of information. Urologists and surgical centres must address this misperception to enable patients to make informed decisions.

Statins have been shown to improve survival of metastatic prostate cancer (mPCa). Nevertheless, their therapeutic use is still under debate. In the present study, we investigated the short-term effects of three different statins (simvastatin, atorvastatin and rosuvastatin) in various PCa cell lines mimicking androgen-sensitive and -insensitive PCa. Moreover, we generated three new PCa cell lines (LNCaPsim, ABLsim, PC-3sim) that were cultured with simvastatin over several months. Our data showed that the three statins expressed highly diverse short-term effects, with the strongest growth-inhibitory effect from simvastatin in PC-3 cells and almost no effect from rosuvastatin in any of the cell lines. Long-term treatment with simvastatin resulted in a loss of response to statins in all three cell lines, which was associated with an upregulation of cholesterol and fatty acid pathways as revealed through RNA sequencing. Despite that, long-term treated cells exhibited diminished spheroid growth and significantly reduced migration capacity per se and to differentiated osteoclasts. These findings were strengthened by reduced expression of genes annotated to cell adhesion and migration after long-term simvastatin treatment. Notably, mPCa patients taking statins were found to have lower numbers of circulating tumor cells in their blood with reduced levels of PSA and alkaline phosphatase. Our data suggest that long-term usage of simvastatin hampers the metastatic potential of PCa cells and may therefore be a potential therapeutic drug for mPCa.

Since tissue material is often lacking in metastatic prostate cancer (mPCa), there is increasing interest in using liquid biopsies for treatment decision and monitoring therapy responses. The purpose of this study was to validate the usefulness of circulating tumor cells (CTCs) and plasma-derived cell-free (cf) RNA as starting material for gene expression analysis through qPCR. CTCs were identified upon prostate-specific membrane antigen and/or cytokeratin positivity after enrichment with ScreenCell (Westford, Massachusetts, USA) filters or the microfluidic Parsortix^TM (Guildford, Surrey, United Kingdom) system. Overall, 50% (28/56) of the patients had ≥5 CTCs/7.5 mL of blood. However, CTC count did not correlate with Gleason score, serum PSA, or gene expression. Notably, we observed high expression of CD45 in CTC samples after enrichment, which could be successfully eliminated through picking of single cells. Gene expression in picked CTCs was, however, rather low. In cfRNA from plasma, on the other hand, gene expression levels were higher compared to those found in CTCs. Moreover, we found that PSA was significantly increased in plasma-derived cfRNA of mPCa patients compared to healthy controls. High PSA expression was also associated with poor overall survival, indicating that using cfRNA from plasma could be used as a valuable tool for molecular expression analysis.

Prostate cancer (PCa) is one of the most common cancers in developed countries. The results of large trials indicate that the proportion of PCa attributable to hereditary factors is as high as 15%, highlighting the importance of genetic testing. Despite improved understanding of the prevalence of pathogenic variants among men with PCa, it remains unclear which men will most benefit from genetic testing. In this review, we summarize recent evidence on genetic testing in primary PCa and its impact on routine clinical practice. We outline current guideline recommendations on genetic testing, most importantly, for mutations in BRCA1/2, MMR, CHEK2, PALB2, and HOXB13 genes, as well as various single nucleotide polymorphisms associated with an increased risk of developing PCa. The implementation of genetic testing in clinical practice, especially in young patients with aggressive tumors or those with positive family history, represents a new challenge for the coming years and will identify men with pathogenic variants who may benefit from early screening/intervention and specific therapeutic options.

A solely retroperitoneal mass in males in combination with elevated serum Alpha-Fetoprotein (AFP) and beta-human choriogonadotropin (β-HCG) levels is highly indicative of a metastatic testicular cancer. Although testicular cancers are rare, they represent the most common diagnosed cancer in males between 14 and 40 years. However, in cases without evidence of a primary testicular tumor, the rare diagnosis of a retroperitoneal extragonadal germ cell tumor (EGCT) must be assumed. Here, we describe the first published case of a 66-year-old man presenting with this typical clinical picture and the diagnosis of an AFP and β-HCG producing advanced gastric cancer with retroperitoneal lymph node metastases mimicking a primary retroperitoneal EGCT. The final diagnosis was only made by gastroscopy performed after a CT-guided retroperitoneal lymph node biopsy revealed an adenocarcinoma, suggesting an upper gastrointestinal tract primary origin. However, a specific initial anamnesis and also in the primary staging, including a full-body CT-scan there was no hint for another primary tumor. Only the slightly unusual extension of the retroperitoneal mass up to the ligamentum hepatoduodenale and the pylorus, as well as the atypical age made us question our initial diagnosis. This extraordinary case is of special clinical interest to all practising physicians and once again highlights the importance of keeping rare differential diagnosis such as AFP-producing gastrointestinal tumors in mind.

Background: This study was conducted in order to analyze factors predicting malignancy in patients undergoing organ-sparing surgery (OSS) for small testicular lesions. Methods: Patients with small (≤20 mm) marker-negative clinical stage I testicular tumors were managed by OSS with tumor enucleation and frozen section examination (FSE) for the past 15 years at our institution. Benign and malignant cases were compared, focusing on preoperative and postoperative lesion sizes. Results: Eighty-nine patients were enrolled in this retrospective study. Ten (11.2%) of them were treated for synchronous bilateral tumors. Sixty-seven (67.7%) of ninety-nine lesions were benign, confirming a high concordance rate (98%) between FSE and final histology. Patients with benign tumors were significantly older than patients with malignant tumors (p = 0.026), and benign tumors were detected more frequently during urologic work-up of hormone disorders (p = 0.001). Preoperative tumor size was a strong predictor of malignancy (area under the curve (AUC) = 0.726; p < 0.001). According to the Youden index, the best cutoff to predict tumor dignity was 13.5 mm, resulting in a sensitivity and specificity of 53% and 85%, respectively. No cases of local recurrence or distant metastasis were confirmed after a median follow-up of 42 months. Conclusion: Our findings are consistent with previous reports, supporting an OSS approach in small testicular tumors whenever possible. Most tumors ≤ 20 mm were benign, and in the case of malignancy, OSS with FSE and consecutive orchiectomy is oncologically safe due to the high concordance rate of FSE and final histology, thus preventing a two-stage procedure.