A Systematic Review and Meta-analysis of the Impact of Local Therapies on Local Event Suppression in Metastatic Hormone-sensitive Prostate Cancer.

CONTEXT: It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). However, data suggest a benefit of these therapies in preventing local events secondary to local tumor progression. OBJECTIVE: To evaluate the efficacy of adding local therapy (RP or RT) to systemic therapies, including androgen deprivation therapy, docetaxel, and/or androgen receptor axis-targeted agents, in preventing local events in mHSPC patients compared with systemic therapy alone (ie, without RT of the prostate or RP). EVIDENCE ACQUISITION: Three databases and meeting abstracts were queried in November 2023 for studies analyzing mHSPC patients treated with local therapy. The primary outcome of interest was the prevention of overall local events (urinary tract infection, urinary tract obstruction, and gross hematuria) due to local disease progression. Subgroup analyses were conducted to assess the differential outcomes according to the type of local therapy (RP or RT). EVIDENCE SYNTHESIS: Overall, six studies, comprising two randomized controlled trials, were included for a systematic review and meta-analysis. The overall incidence of local events was significantly lower in the local treatment plus systemic therapy group than in the systemic therapy only groups (relative risk [RR]: 0.50, 95% confidence interval [CI]: 0.28-0.88, p = 0.016). RP significantly reduced the incidence of overall local events (RR: 0.24, 95% CI: 0.11-0.52) and that of local events requiring surgical intervention (RR: 0.08, 95% CI: 0.03-0.25). Although there was no statistically significant difference between the RT plus systemic therapy and systemic therapy only groups in terms of overall local events, the incidence of local events requiring surgical intervention was significantly lower in the RT plus systemic therapy group (RR: 0.70, 95% CI: 0.49-0.99); local events requiring surgical intervention of the upper urinary tract was significantly lower in local treatment groups (RR: 0.60, 95% CI: 0.37-0.98, p = 0.04). However, a subgroup analysis revealed that neither RP nor RT significantly impacted the prevention of local events requiring surgical intervention of the upper urinary tract. CONCLUSIONS: In some patients with mHSPC, RP or RT of primary tumor seems to reduce the incidence of local progression and events requiring surgical intervention. Identifying which patients are most likely to benefit from local therapy, and at what time point (eg, after response of metastases), will be necessary to set up a study assessing the risk, benefits, and alternatives to therapy of the primary tumor in the mHSPC setting. PATIENT SUMMARY: Our study suggests that local therapy of the prostate, such as radical prostatectomy or radiotherapy, in patients with metastatic hormone-sensitive prostate cancer can prevent local events, such as urinary obstruction and gross hematuria.

Radiotherapy in localized prostate cancer: a multicenter analysis evaluating tumor control and late toxicity after brachytherapy and external beam radiotherapy in 1293 patients.

BACKGROUND AND PURPOSE: Comparing oncological outcomes and toxicity after primary treatment of localized prostate cancer using HDR- or LDR-mono-brachytherapy (BT), or conventionally (CF) or moderately hypofractionated (HF) external beam radiotherapy. MATERIALS AND METHODS: Retrospectively, patients with low- (LR) or favorable intermediate-risk (IR) prostate cancer treated between 03/2000 and 09/2022 in two centers were included. Treatment was performed using either CF with total doses between 74 and 78 Gy, HF with 2.4-2.6 Gy per fraction in 30 fractions, or LDR- or HDR-BT. Biochemical control (BC) according to the Phoenix criteria, and late gastrointestinal (GI), and genitourinary (GU) toxicity according to RTOG/EORTC criteria were assessed. RESULTS: We identified 1293 patients, 697 with LR and 596 with IR prostate cancer. Of these, 470, 182, 480, and 161 were treated with CF, HF, LDR-BT, and HDR-BT, respectively. For BC, we did not find a significant difference between treatments in LR and IR (p = 0.31 and 0.72). The 5­year BC for LR was between 93 and 95% for all treatment types. For IR, BC was between 88% in the CF and 94% in the HF group. For CF and HF, maximum GI and GU toxicity grade ≥ 2 was between 22 and 27%. For LDR-BT, we observed 67% grade ≥ 2 GU toxicity. Maximum GI grade ≥ 2 toxicity was 9%. For HDR-BT, we observed 1% GI grade ≥ 2 toxicity and 19% GU grade ≥ 2 toxicity. CONCLUSION: All types of therapy were effective and well received. HDR-BT caused the least late toxicities, especially GI.

Metastasis-directed therapy in oligometastatic prostate cancer.

PURPOSE OF REVIEW: To summarize the recent findings on the subject of metastasis-directed therapy (MDT) in the treatment of oligometastatic prostate cancer (omPCa). RECENT FINDINGS: Evidence from two randomized clinical trials (RCTs) and a meta-analysis show favorable toxicity profiles, and the potential to delay androgen-deprivation therapy (ADT) for up to two years in nearly half of patients with metachronous hormone-sensitive omPCa. Another RCT showed promising results of MDT as treatment-escalation method combined with androgen receptor signaling inhibitors (ARSI) in first-line treatment for castration-resistant omPCa.Surveys by radiation oncologists and consensus guidelines advocate for MDT across various omPCa scenarios. Multiple single-arm trials present encouraging results; however, the evidence for the benefit of MDT is still weak requiring further investigation to assess its impact on pivotal endpoints, such as survival and quality of life. SUMMARY: MDT is a promising approach in omPCa, and can be used to defer ADT in newly diagnosed metachronous omPCa patients, or to add to ARSI treatment at first diagnosis of castration-resistance. Ongoing prospective trials are needed to guide its optimal utilization in other settings, and patients should be informed about the evolving landscape of systemic therapies with proven survival benefits alongside MDT options.

Comparing the Performance of Digital Rectal Examination and Prostate-specific Antigen as a Screening Test for Prostate Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Although digital rectal examination (DRE) is recommended in combination with prostate-specific antigen (PSA) for detection of prostate cancer (PCa), there are limited data to support its use as a screening/early detection test. Our objective was to assess the diagnostic value of DRE in screening for early detection of PCa. METHODS: In August 2023, we queried the PubMed, Scopus, and Web of Science databases to identify prospective studies simultaneously investigating the diagnostic performance of DRE and PSA for PCa screening. The primary endpoints were the positive predictive value (PPV) and cancer detection rate (CDR) of DRE. Secondary endpoints included the PPV and CDR of both PSA alone and in combination with DRE. We conducted meta-regression analysis to compare the CDR and PPV of different screening strategies. This meta-analysis is registered on PROSPERO (CRD42023446940). KEY FINDINGS AND LIMITATIONS: We identified eight studies involving 85 738 participants, of which three were randomized controlled trials and five were prospective diagnostic studies, that reported the PPV and CDR of both DRE and PSA for the same cohort. Our analysis revealed a pooled PPV of 0.21 (95% confidence interval [CI] 0.13-0.33) for DRE, which is similar to the PPV of PSA (0.22, 95% CI 0.15-0.30; p = 0.9), with no benefit from combining DRE and PSA (PPV 0.19, 95% CI 0.13-0.26; p = 0.5). However, the CDR of DRE (0.01, 95% CI: 0.01-0.02) was significantly lower than that of PSA (0.03, 95% CI 0.02-0.03; p < 0.05) and the combination of DRE and PSA (0.03, 95% CI 0.02-0.04; p < 0.05). The screening strategy combining DRE and PSA was not different to that of PSA alone in terms of CDR (p = 0.5) and PPV (p = 0.5). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our comprehensive review and meta-analysis indicates that both as an independent test and as a supplementary measure to PSA for PCa detection, DRE exhibits a notably low diagnostic value. The collective findings from the included studies suggest that, in the absence of clinical symptoms and signs, DRE could be potentially omitted from PCa screening and early detection strategies. PATIENT SUMMARY: Our review shows that the screening performance of digital rectal examination for detection of prostate cancer is not particularly impressive, suggesting that it might not be necessary to conduct this examination routinely.

Sexual activity in a large representative cohort of Polish men: Frequency, number of partners, correlates, and quality of life.

INTRODUCTION: Sexual activity of men has been evaluated at the population-level in different regions of the world. However, reliable data are lacking for Eastern Europe. Therefore, the aim of this study was to analyze the frequency of sexual activity and the number of sexual partners in a large representative cohort of Polish men. METHODS: We performed a cross-sectional investigation with computer-assisted web interviews. Participants were stratified by age (≥18 years) and place of residence. The most recent population census was used to produce a population-representative sample of respondents. Men's sexual activity was then correlated with multiple variables. RESULTS: We enrolled 3001 men, representative for age and place of residence, including adequate proportions of respondents from urban and rural areas. Most Polish men were sexually active, predominantly having had sex at least weekly with one partner. Almost 18% of respondents declined sexual intercourse and/or sexual partner in the prior year. The highest sexual activity was observed for men 35-44-years-old (for sex frequency) and 18-24-years-old (for partner number), living in medium-sized cities, employed, and married (for sex frequency) or divorced (for partner number). Erectile dysfunction negatively affected the frequency of sexual activity and lowered the number of sexual partners, although premature ejaculation did not have any effect. Frequency of sexual activity and number of sexual partners correlated well with psychological distress, quality of sex life, and overall life quality. Whereas lifestyle habits including smoking and alcohol intake decreased the likelihood of sexual activity, all analyzed comorbidities did not affect sex life. CONCLUSIONS: This study of men's sexual activity was the first population-representative and nationwide investigation performed in Poland. Most Polish men were sexually active and sexual activity correlated with multiple variables including sociodemographic factors, erectile functioning, mental distress, overall and sex-specific quality of life, and lifestyle habits.

The Efficacy and Safety of Metastasis-directed Therapy in Patients with Prostate Cancer: A Systematic Review and Meta-analysis of Prospective Studies.

CONTEXT: Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies. OBJECTIVE: To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients. EVIDENCE ACQUISITION: We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators. EVIDENCE SYNTHESIS: We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and ≥3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively. CONCLUSIONS: MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain. PATIENT SUMMARY: Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.

Current trends in non-surgical management of Peyronie's disease-A narrative review.

Peyronie's disease (PD) is a connective tissue disorder affecting the tunica albuginea. It can cause pain and penile deformation, and its prevalence increases with age. Although surgery is the gold standard for the chronic phase of the disease, there are several conservative treatment methods available, and the optimal management of the acute phase of the disease remains a matter of debate. In this article, we aim to summarize the recent trends in research on the subject of non-surgical treatment of PD. The search was performed in PubMed, Scopus, and Web of Science databases and included studies in English published between 2012 and 2022 investigating the clinical outcomes of non-surgical PD management in humans. We have identified 20 distinct conservative treatment strategies. Among the oral therapeutics, only the use of phosphodiesterase type 5 inhibitors is currently recommended for clinical use in patients with concomitant erectile dysfunction. The use of collagenase from Clostridium histolyticum is supported by the best quality evidence in terms of intralesional injections for patients suffering from significant penile curvature; however, interferon alpha-2b can also be an option in such patients. Among other non-invasive methods, extracorporeal shockwaves can be useful for pain reduction, and penile traction therapy can lead to a reduction in penile curvature and plaque size. Despite a wide range of non-surgical methods available for PD treatment, the majority are not supported by sufficient scientific evidence, and the treatment efficacy is underwhelming. Further research on the subject of non-surgical management of PD is highly warranted.

Stereotactic body radiotherapy (SBRT) re-irradiation for local failures following radical prostatectomy and post-operative radiotherapy.

PURPOSE: Local recurrences after radical prostatectomy (RP) and postoperative radiotherapy (RT) are challenging for salvage treatment. Retrospective analysis of own experiences with salvage re-irradiation was performed. METHODS: The study included all consecutive patients treated with salvage stereotactic body radiotherapy (sSBRT) for prostate bed recurrence following RP and postoperative RT at a single tertiary center between 2014 and 2021. Treatment toxicity defined as the occurrence of CTCAE grade ≥ 2 genito-urinary (GU) or gastro-intestinal (GI) adverse events (AEs) was assessed. A PSA response, biochemical control (BC) and overall survival (OS) were also evaluated. RESULTS: The study group included 32 patients with a median age of 68 years and a median follow-up of 41 months, treated with CyberKnife (53%) or Linac (47%) sSBRT. Total dose of 33.75-36.25 Gy in five fractions (72%) was applied in the majority of them. Approximately 19% patients reported grade ≥ 2 GU AEs both at baseline and at three months, and grade ≥ 2 GI toxicity increased from 0% at baseline to 6% at three months after sSBRT. There was some clinically relevant increase in late toxicity with 31% patients reporting late ≥ 2 GU, and 12.5% late ≥ 2 GI AEs. Two grade 3 AEs were recorded: recto-urinary fistulas. The majority of patients showed a PSA response (91% at one year post-sSBRT). The 3­year BC was 40% and 3­year OS was 87%. CONCLUSIONS: Manageable toxicity profile and satisfactory biochemical response suggest that SBRT in patients with local recurrence following RP and postoperative RT might be a salvage option for selected patients.

Rectum and Bladder Toxicity in Postoperative Prostate Bed Irradiation: Dose-Volume Parameters Analysis.

Although prostate cancer treatment is increasingly effective, its toxicities pose a major concern. The aim of our study was to assess the rate of adverse events (AEs) and the prognostic value of dose-volume histogram (DVH) parameters for the occurrence of treatment toxicity in patients treated with post-prostatectomy prostate bed radiotherapy (RT). The AEs were scored according to the CTCAE v.5.0. The rectum and bladder were contoured according to the RTOG Guidelines. The DVH parameters were assessed using data exported from the ECLIPSE treatment-planning system. Genitourinary (GU) and gastrointestinal (GI) toxicity were analysed using consecutive dose thresholds for the percentage of an organ at risk (OAR) receiving a given dose and the QUANTEC dose constraints. A total of 213 patients were included in the final analysis. Acute grade 2 or higher (≥G2) GU AEs occurred in 18.7% and late in 21.3% of patients. Acute ≥G2 GI toxicity occurred in 11.7% and late ≥G2 in 11.2% of the patients. Five patients experienced grade 4 AEs. The most common adverse effects were diarrhoea, proctitis, cystitis, and dysuria. The most significant predictors of acute ≥G2 GI toxicity were rectum V47 and V46 (p < 0.001 and p < 0.001) and rectum wall V46 (p = 0.001), whereas the most significant predictors of late ≥G2 GI AEs were rectum wall V47 and V48 (p = 0.019 and p = 0.021). None of the bladder or bladder wall parameters was significantly associated with the risk of acute toxicity. The minimum doses to bladder wall (p = 0.004) and bladder (p = 0.005) were the most significant predictors of late ≥G2 GU toxicity. Postoperative radiotherapy is associated with a clinically relevant risk of AEs, which is associated with DVH parameters, and remains even in patients who fulfil commonly accepted dose constraints. Considering the lack of survival benefit of postoperative adjuvant RT, our results support delaying treatment through an early salvage approach to avoid or defer toxicity.

Outcomes of Cytoreductive Radical Prostatectomy for Oligometastatic Prostate Cancer on Prostate-specific Membrane Antigen Positron Emission Tomography: Results of a Multicenter European Study.

BACKGROUND: De novo oligometastatic prostate cancer (omPCa) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a new disease entity and its optimal management remains unknown. OBJECTIVE: To analyze the outcomes of patients treated with cytoreductive radical prostatectomy (cRP) for omPCa on PSMA-PET. DESIGN, SETTING, AND PARTICIPANTS: Overall, 116 patients treated with cRP at 13 European centers were identified. Oligometastatic PCa was defined as miM1a and/or miM1b with five or fewer osseous metastases and/or miM1c with three or fewer lung lesions on PSMA-PET. INTERVENTION: Cytoreductive radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Thirty-day complications according to Clavien-Dindo, continence rates, time to castration-resistant PCa (CRPC), and overall survival (OS) were analyzed. RESULTS AND LIMITATIONS: Overall, 95 (82%) patients had miM1b, 18 (16%) miM1a, and three (2.6%) miM1c omPCa. The median prebiopsy prostate-specific antigen was 14 ng/ml, and 102 (88%) men had biopsy grade group ≥3 PCa. The median number of metastases on PSMA-PET was 2; 38 (33%), 29 (25%), and 49 (42%) patients had one, two, and three or more distant positive lesions. A total of 70 (60%) men received neoadjuvant systemic therapy, and 37 (32%) underwent metastasis-directed therapy. Any and Clavien-Dindo grade ≥3 complications occurred in 36 (31%) and six (5%) patients, respectively. At a median follow-up of 27 mo, 19 (16%) patients developed CRPC and eight (7%) patients died. The 1-yr urinary continence rate was 82%. The 2-yr CRPC-free survival and OS were 85.8% (95% confidence interval [CI] 78.5-93.7%) and 98.9% (95% CI 96.8-100%), respectively. The limitations include retrospective design and short-term follow-up. CONCLUSIONS: Cytoreductive radical prostatectomy is a safe and feasible treatment option in patients with de novo omPCa on PSMA-PET. Despite overall favorable oncologic outcomes, some of these patients have a non-negligible risk of early progression and thus should be considered for multimodal therapy. PATIENT SUMMARY: We found that patients treated at expert centers with surgery for prostate cancer, with a limited number of metastases detected using novel molecular imaging, have favorable short-term survival, functional results, and acceptable rates of complications.

Salvage re-irradiation in non-melanoma skin cancers: A multicenter analysis.

BACKGROUND AND PURPOSE: We conducted a multicentre real-world study to assess the outcomes of radical salvage re-irradiation for non-melanoma skin cancer (nMSC) recurrences following definitive or postoperative radiotherapy. MATERIALS AND METHODS: Data on patients treated between 2006 and 2022 with re-irradiation for nMSCs were retrospectively collected from five high-volume brachytherapy centers. The primary endpoint was local control (LC). Secondary endpoints included overall survival, progression-free survival, and adverse events (AEs). The Kaplan-Meier estimator and Cox Proportional-Hazards Model were utilised in the analysis. RESULTS: A total of 58 patients with a median age of 78.4 years with recurrences of previously irradiated nMSC in the head and neck region were included in the analysis. The majority had cutaneous basal cell carcinoma (BCC; 91.4%), and were irradiated with high-dose-rate brachytherapy (HDR-BT; 91.4%). The most common locations included the nasal region (36.2%) and external ear (18.9%). The 1-year LC was 73.1% and decreased to 41.7% at three years. The size of the re-irradiated lesion was the single independent prognostic factor in Cox analysis (per mm; HR 1.07; 95% CI 1.04-1.11; p < 0.001). Grade 3 or worse AEs were reported in 7 cases (12.1%). CONCLUSION: Re-irradiation for nMSCs, predominantly administered with brachytherapy for radiorecurrent BCC, is associated with high recurrence rates, and the risk of failure significantly increases with the size of the treated lesion. Re-irradiation could be an option for selected elderly patients with small, localised, inoperable recurrences after RT to achieve local control or defer systemic treatment; however, prospective trials are necessary to confirm its safety and efficacy.

Refining critical structure contouring in STereotactic Arrhythmia Radioablation (STAR): Benchmark results and consensus guidelines from the STOPSTORM.eu consortium.

BACKGROUND AND PURPOSE: In patients with recurrent ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) shows promising results. The STOPSTORM.eu consortium was established to investigate and harmonise STAR treatment in Europe. The primary goals of this benchmark study were to standardise contouring of organs at risk (OAR) for STAR, including detailed substructures of the heart, and accredit each participating centre. MATERIALS AND METHODS: Centres within the STOPSTORM.eu consortium were asked to delineate 31 OAR in three STAR cases. Delineation was reviewed by the consortium expert panel and after a dedicated workshop feedback and accreditation was provided to all participants. Further quantitative analysis was performed by calculating DICE similarity coefficients (DSC), median distance to agreement (MDA), and 95th percentile distance to agreement (HD95). RESULTS: Twenty centres participated in this study. Based on DSC, MDA and HD95, the delineations of well-known OAR in radiotherapy were similar, such as lungs (median DSC = 0.96, median MDA = 0.1 mm and median HD95 = 1.1 mm) and aorta (median DSC = 0.90, median MDA = 0.1 mm and median HD95 = 1.5 mm). Some centres did not include the gastro-oesophageal junction, leading to differences in stomach and oesophagus delineations. For cardiac substructures, such as chambers (median DSC = 0.83, median MDA = 0.2 mm and median HD95 = 0.5 mm), valves (median DSC = 0.16, median MDA = 4.6 mm and median HD95 = 16.0 mm), coronary arteries (median DSC = 0.4, median MDA = 0.7 mm and median HD95 = 8.3 mm) and the sinoatrial and atrioventricular nodes (median DSC = 0.29, median MDA = 4.4 mm and median HD95 = 11.4 mm), deviations between centres occurred more frequently. After the dedicated workshop all centres were accredited and contouring consensus guidelines for STAR were established. CONCLUSION: This STOPSTORM multi-centre critical structure contouring benchmark study showed high agreement for standard radiotherapy OAR. However, for cardiac substructures larger disagreement in contouring occurred, which may have significant impact on STAR treatment planning and dosimetry evaluation. To standardize OAR contouring, consensus guidelines for critical structure contouring in STAR were established.

Stereotactic management of arrhythmia - radiosurgery in treatment of ventricular tachycardia (SMART-VT). Results of a prospective safety trial.

BACKGROUND AND PURPOSE: Despite its increasing popularity, there are limited prospective data on stereotactic arrhythmia radioablation (STAR). In this trial, we assessed the safety and efficacy of STAR in patients with ventricular tachycardia (VT), focusing on early treatment-related grade ≥ 3 adverse events (AE). MATERIALS AND METHODS: This prospective trial was designed for adults with VT recurrence following catheter ablation (CA) despite adequate pharmacotherapy, or contraindications to CA. A single dose of 25 Gy was delivered to the arrhythmia substrate defined on electro-anatomic mapping and cardiac-gated CT. The primary endpoint was safety, defined as two or fewer treatment-related grade ≥ 3 AEs during the first three months in 11 patients. Additional endpoints included treatment efficacy, clinical and biological markers of cardiac injury, and quality of life. RESULTS: Eleven patients with a median age of 67 years, structural heart disease, and a clinically significant recurrence of VT despite adequate pharmacotherapy and 1-4 previous CAs were enrolled between 2020/09 and 2022/10. Following the treatment, one patient developed a possibly treatment-related grade ≥ 3 AE, a grade 4 heart failure exacerbation at 87 days, which resolved after conservative treatment. There was a total 84.3% reduction in VT burden in 10 evaluable patients; however, VT recurrence was eventually observed in eight, and three patients required additional CAs. Three deaths due to unrelated causes were recorded. CONCLUSIONS: STAR appears to be safe and efficient. It is a promising treatment for selected patients; however, long-term outcomes remain to be evaluated, and controlled trials comparing STAR with standards of care are missing.

Survival outcomes of patients treated with local therapy for nonmetastatic prostate cancer with high prostate-specific antigen concentrations.

BACKGROUND: Patients with nonmetastatic prostate cancer (nmPCa) and high prostate-specific antigen (PSA) levels due to the high likelihood of metastasis pose a clinical dilemma regarding their optimal treatment and long-term outcomes after initial local therapy. We aimed to evaluate the oncologic outcomes of patients treated with radical prostatectomy (RP) or radiotherapy (RT) for nmPCa with high PSA levels. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with nmPCa who received RP or RT from 2004 through 2015. We included nmPCa patients with high PSA levels categorized as ≥50 and ≥98 ng/mL, the highest level recorded in SEER. We used the Kaplan-Meier method and Cox proportional hazards to analyze cancer-specific (CSS) and overall survival (OS). RESULTS: We included 6177 patients with nmPCa and PSA ≥ 50 ng/mL at diagnosis; 1698 (27%) had PSA ≥ 98 ng/mL. Of these, 1658 (26.8%) underwent RP and 4519 (73.16%) patients received primary RT. Within a median of 113 months (interquartile range 74-150 months), the 5- and 10-year CSS estimates were 92.3% and 81.5% respectively; 10-year OS was 61%. In the PSA ≥ 98 ng/mL subgroup 5- and 10-year CSS estimates were 89.2% and 76%, respectively. In multivariable analyses for CSS, ISUP grade group (p < 0.001), N stage (p < 0.001), treatment with RP (hazard ratio [HR] = 0.60, 95% confidence interval [CI] 0.43-0.83, p < 0.001), and patient's age (p < 0.05) were associated with improved CSS. In the whole cohort of patients with PSA ≥ 50 ng/mL and RP subgroup, PSA failed to retain its independent prognostic value for CSS. CONCLUSIONS: Patients treated with local therapy for nmPCa with very high PSA at diagnosis have relatively good long-term oncological outcomes. Therefore, among well-selected patients with nmPCa, high PSA levels alone should not preclude the use of radical local therapy. Potential selection bias limits inferences about the relative effectiveness of specific local therapies in this setting.

Intracranial Germinoma-Association between Delayed Diagnosis, Altered Clinical Manifestations, and Prognosis.

BACKGROUND: Intracranial germinoma is a rare malignant neoplasm of the central nervous system (CNS) that occurs in children and young adults. The aim of our study was to assess the initial manifestation of the disease, and to find differences in outcomes dependent on time of diagnosis. METHODS: The study group consisted of 35 consecutive patients (adults and children) who were treated for intracranial germinoma with radiotherapy at a tertiary centre, and their data were retrospectively collected. We evaluated time from the first symptoms to diagnosis and divided patients into early and delayed diagnosis groups. Delayed diagnosis has been defined as the time from initial presentation to final diagnosis longer than six months. RESULTS: A total of 17 (48.6%) of the patients had delayed diagnoses. Patient survival data spanned a median of six (interquartile range 3-12) years. At the time of the diagnosis, patients presented exclusively neurological symptoms in 16 (45.7%) cases, exclusively endocrinological symptoms in five (14.3%) cases, and mixed symptoms in the remaining cases (n = 14; 40.0%). Patients with neurological symptoms had shorter time (p < 0.001) from first symptoms to the final diagnosis (5.91 months) than in patients without them (19.44 months). The delayed diagnosis group presented significantly smaller tumour size (mean maximal dimension 2.35 cm) compared to early diagnosis group (3.1 cm). The 5-year and 10-year survival rates of our patients were 94.3% and 83.4%, respectively. Patients with a delayed diagnosis (n = 17) had a significantly worse (p = 0.02) 10-year OS (63%) compared to the early diagnosis group (n = 18; OS = 100%). Importantly, in five patients (14.29%), initial manifestation occurred before radiological signs of the disease. CONCLUSION: Our study stresses the need for timely diagnosis in intracranial germinoma, as a delay has a significant impact on the prognosis. In particular, if the tumour is small or causes exclusively endocrinological symptoms, the diagnosis may be difficult and delayed.

Brachytherapy boost improves survival and decreases risk of developing distant metastases compared to external beam radiotherapy alone in intermediate and high risk group prostate cancer patients.

BACKGROUND AND PURPOSE: Despite several prospective trials showing a clinical benefit of combining external beam radiotherapy (EBRT) with brachytherapy boost (BTB) for the treatment of intermediate- and high-risk prostate cancer (PCa) patients, none of these trials was designed to test for a survival difference. In this study, we aimed to collect a large multi-institutional database to determine whether BT boost was associated with a statistically significant improvement in survival and a reduction of distant metastases based on real-world data. MATERIAL AND METHODS: We collected the data of patients treated for intermediate- or high-risk PCa with definitive EBRT or BTB, with or without androgen deprivation therapy (ADT), between January 2003 and December 2014 at two tertiary institutions. The statistical endpoints included overall survival (OS), freedom from distant metastases (FFDM), and metastases-free survival (MFS). The impact of treatment modality was assessed using Cox regression models and log-rank testing after one-to-one propensity score matching. RESULTS: A total of 1641 patients treated with EBRT (n = 1148) or high-dose-rate BTB (n = 493) were analyzed. The median survival and clinical follow-up were 117.8 (IQR 78-143.3) and 60.7 months, respectively. The radiotherapy modality (BTB) remained an independent prognostic factor for OS (HR 0.75; 95% CI 0.63-0.88; p < 0.001), FFDM (HR 0.54; 95% CI 0.4-0.73; p < 0.001), and MFS (HR 0.72; 95% CI 0.61-0.85; p < 0.001). After propensity score matching, the remaining 986 patients were well-balanced in terms of age, maximum PSA, ISUP grade group, and TNM T stage. OS (p < 0.001), FFDM (p = 0.001) and MFS (p < 0.001) were significantly higher in the BTB group. CONCLUSIONS: There is a strong positive association between BTB and OS, FFDM, and MFS in PCa patients treated with definitive RT for intermediate- or high-risk PCa.

STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

Long-Term Outcomes of Stereotactic Body Radiotherapy (SBRT) for Intraprostatic Relapse after Definitive Radiotherapy for Prostate Cancer: Patterns of Failure and Association between Volume of Irradiation and Late Toxicity.

The aim of this retrospective study was to assess the adverse effects and outcomes of salvage re-irradiation with stereotactic body radiotherapy (sSBRT) for local recurrence of prostate cancer (PCa) after definitive radiotherapy (RT). The study was focused on the adverse effects and prognostic factors for treatment toxicity, followed by an analysis of patterns of failure and survival. Patients treated with sSBRT between 2012 and 2020 at a tertiary institution were included. The exclusion criteria were a primary or salvage radical prostatectomy or a palliative sSBRT dose. Patients with oligorecurrence were eligible if all metastatic lesions were treated locally with curative intent. The Kaplan-Meier method was used to estimate time to grade ≥ 3 toxicity, local control (LC), freedom from distant metastases (FFDM), progression-free survival (PFS), biochemical control (BC) and overall survival (OS). The differences between groups (focal vs. whole-gland sSBRT) were compared using the log-rank test. The Cox proportional hazards model was used to assess prognostic factors for the listed endpoints. A total of 56 patients with a median age of 70.9 years and a median follow-up of 38.6 months were included in the analysis. The majority of them received local sSBRT only (45; 80.4%), while the rest were simultaneously treated for oligometastases (11; 19.6%). Overall, 18 (32.1%) patients experienced any grade ≥ 3 toxicity, including 1 (6.7%) patient who received focal sSBRT, and 17 (41.5%) patients treated with whole-gland sSBRT. The Planning Target Volume (per cc; HR 1.01; 95% CI 1-1.02; p = 0.025) and use of ADT (yes vs. no; HR 0.35; 95%CI 0.13-0.93; p = 0.035) were independent prognostic factors for the risk of grade ≥ 3 toxicity. The estimated rate of grade ≥ 3 adverse events was significantly higher (43.8% vs. 7.1% at 2 years; p = 0.006), and there was no improvement in the LC (92.9% vs. 85.3% at 2 years; p = 0.759) in patients treated with whole-gland sSBRT compared to focal sSBRT. The 2- and 5-year LC were 87.6% and 47.9%, respectively; the 2- and 5-year FFDM were 72.7% and 42.8%, respectively; and the 2- and 5-year PFS were 67.9% and 28.7%, respectively. The primary pattern of failure was distant metastasis. The sSBRT for local recurrence of PCa after definitive RT was associated with a high risk of severe grade ≥ 3 toxicity, which significantly increased with the volume and extent of re-irradiation.

Ultra-Hypofractionated Stereotactic Body Radiotherapy for Localized Prostate Cancer: Clinical Outcomes, Patterns of Recurrence, Feasibility of Definitive Salvage Treatment, and Competing Oncological Risk.

A cohort of 650 patients treated for localized prostate cancer (PCa) with CyberKnifeTM ultra-hypofractionated radiotherapy between 2011 and 2018 was retrospectively analyzed in terms of survival, patterns of failure, and outcomes of second-line definitive salvage therapies. The analysis was performed using survival analysis including the Kaplan-Meier method and Cox regression analysis. At a median follow-up of 49.4 months, the main pattern of failure was local-regional failure (7.4% in low-, and 13% in intermediate/high-risk group at five years), followed by distant metastases (3.6% in low-, and 6% in intermediate/high-risk group at five years). Five-year likelihood of developing a second malignancy was 7.3%; however, in the vast majority of the cases, the association with prior irradiation was unlikely. The 5-year overall survival was 90.2% in low-, and 88.8% in intermediate/high-risk patients. The independent prognostic factors for survival included age (HR 1.1; 95% CI 1.07-1.14) and occurrence of a second malignancy (HR 3.67; 95% CI 2.19-6.15). Definitive local salvage therapies were feasible in the majority of the patients with local-regional failure, and uncommonly in patients with distant metastases, with an estimated second-line progression free survival of 67.8% at two years. Competing oncological risks and age were significantly more important for patients' survival compared to primary disease recurrence.