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Prostate cancer (PCa) is a widespread malignancy with global significance, which substantially affects cancer-related mortality. Its spectrum varies widely, from slow-progressing cases to aggressive or even lethal forms. Effective patient stratification into risk groups is crucial to therapeutic decisions and clinical trials. This review examines a wide range of diagnostic and prognostic biomarkers, several of which are integrated into clinical guidelines, such as the PHI, the 4K score, PCA3, Decipher, and Prolaris. It also explores the emergence of novel biomarkers supported by robust preclinical evidence, including urinary miRNAs and isoprostanes. Genetic alterations frequently identified in PCa, including BRCA1/BRCA2, ETS gene fusions, and AR changes, are also discussed, offering insights into risk assessment and precision treatment strategies. By evaluating the latest developments and applications of PCa biomarkers, this review contributes to an enhanced understanding of their role in disease management. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a critical global public health issue with its incidence on the rise. Radiation therapy holds a primary role in PCa treatment; however, radiation resistance has become increasingly challenging as we uncover more about PCa's pathogenesis. Our review aims to investigate the multifaceted mechanisms underlying radiation therapy resistance in PCa. Specifically, we will examine how various factors, such as cell cycle regulation, DNA damage repair, hypoxic conditions, oxidative stress, testosterone levels, epithelial–mesenchymal transition, and tumor stem cells, contribute to radiation therapy resistance. By exploring these mechanisms, we hope to offer new insights and directions towards overcoming the challenges of radiation therapy resistance in PCa. This can also provide a theoretical basis for the clinical application of novel ultra-high-dose-rate (FLASH) radiotherapy in the era of PCa. [ABSTRACT FROM AUTHOR]

Background: Stereotactic ablative body radiotherapy (SABR) is one of the treatment options for oligometastatic renal cell carcinoma (RCC) but is limited by a lack of data to evaluate high-dose SABR to all/multiple sites. Objective: This study retrospectively investigated the efficacy and prognostic factors of high-dose SABR for oligometastatic RCC patients. Design, setting, and participants: Patients with oligometastatic RCC on systemic therapy were retrospectively collected. Intervention(s): All patients were treated with SABR (40–50 Gy/5 fractions) for small tumors or partial-SABR (tumor center boosted with 6–8 Gy/3–5 fractions with 50–60 Gy/20–25 fractions to the whole tumor volume) for bulky tumors or tumors adjacent to critical organs. Outcome measurements and statistical analysis: Progression-free survival (PFS) and overall survival (OS) were calculated. Results and limitations: In total, 35 patients were enrolled, of which 88.5% had intermediate- or high-risk disease, with 60% on second- to fourth-line systemic therapy. The median follow-up time was 17 months. The median PFS and OS times were 11.3 and 29.7 months, respectively. Univariate analysis showed that an OS benefit was found in patients who received radiation before tyrosine kinase inhibitor (TKI) failure (p = 0.006) and where there was a short time interval (

Purpose: To evaluate dosimetric properties of intensity‐modulated proton therapy (IMPT) for simulated treatment planning in patients with atrial fibrillation (AF) targeting left atrial‐pulmonary vein junction (LA‐PVJ), in comparison with volumetric‐modulated arc therapy (VMAT) and helical tomotherapy (TOMO). Methods: Ten thoracic 4D‐CT scans with respiratory motion and one with cardiac motion were used for the study. Ten respiratory 4D‐CTs were planned with VMAT, TOMO, and IMPT for simulated AF. Targets at the LA‐PVJ were defined as wide‐area circumferential ablation line. A single fraction of 25 Gy was prescribed to all plans. The interplay effects from cardiac motion were evaluated based on the cardiac 4D‐CT scan. Dose‐volume histograms (DVHs) of the ITV and normal tissues were compared. Statistical analysis was evaluated via one‐way Repeated‐Measures ANOVA and Friedman's test with Bonferroni's multiple comparisons test. Results: The median volume of ITV was 8.72cc. All plans had adequate target coverage (V23.75Gy ≥ 99%). Compared with VMAT and TOMO, IMPT resulted in significantly lower dose of most normal tissues. For VMAT, TOMO, and IMPT plans, Dmean of the whole heart was 5.52 ± 0.90 Gy, 5.89 ± 0.78 Gy, and 3.01 ± 0.57 Gy (P < 0.001), mean dose of pericardium was 4.74 ± 0.76 Gy, 4.98 ± 0.62 Gy, and 2.59 ± 0.44 Gy (P < 0.001), and D0.03cc of left circumflex artery (LCX) was 13.96 ± 5.45 Gy, 14.34 ± 5.91 Gy, and 8.43 ± 7.24 Gy (P < 0.001), respectively. However, no significant advantage for one technique over the others was observed when examining the D0.03cc of esophagus and main bronchi. Conclusions: IMPT targeting LA‐PVJ for patients with AF has high potential to reduce dose to surrounding tissues compared to VMAT or TOMO. Motion mitigation techniques are critical for a particle‐therapy approach. [ABSTRACT FROM AUTHOR]

Background: It is not known which risk stratification system has the best discrimination ability for predicting prostate cancer death. Methods: We identified patients with non-metastatic primary prostate adenocarcinoma diagnosis between 2004 and 2015 using the Surveillance, Epidemiology, and End Results database. Patients were categorized in different risk groups using the three frequently used risk stratification systems of the National Comprehensive Cancer Network guideline (NCCN-g), American Urological Association guideline (AUA-g), and European Association of Urology guideline (EAU-g), respectively. Associations between risk classification and prostate cancer-specific mortality (PCSM) were determined using Kaplan–Meier analyses and multivariable regression with Cox proportional hazards model. Area under the receiver operating characteristics curve (AUC) analyses were used to test the discrimination ability of the three risk grouping systems. Results: We analyzed 310,062 patients with a median follow-up of 61 months. A total of 36,368 deaths occurred, including 6,033 prostate cancer deaths. For all the three risk stratification systems, the risk groups were significantly associated with PCSM. The AUC of the model relying on NCCN-g, AUA-g, and EAU-g risk stratification systems for PCSM at specifically 8 years were 0.818, 0.793, and 0.689 in the entire population; 0.819, 0.795, and 0.691 in Whites; 0.802, 0.777, and 0.681 in Blacks; 0.862, 0.818, and 0.714 in Asians; 0.845, 0.806, and 0.728 in Chinese patients. Regardless of the age, marital status, socioeconomic status, and treatment modality, AUC of the model relying on NCCN-g and AUA-g for PCSM was greater than that relying on EAU-g; AUC of the model relying on NCCN-g system was greater than that of the AUA-g system. Conclusions: The NCCN-g and AUA-g risk stratification systems perform better in discriminating PCSM compared to the EAU-g system. The discrimination ability of the NCCN-g system was better than that of the AUA-g system. It is recommended to use NCCN-g to evaluate risk groups for prostate cancer patients and then provide more appropriate corresponding treatment recommendations. [ABSTRACT FROM AUTHOR]

Patients with advanced renal cancer (RCC) often have limited success with systemic therapy due to tumor heterogeneity. However, stereotactic ablative radiotherapy (SABR) has been shown to have a beneficial therapeutic effect for oligometastatic disease when used early. Despite this, current guidelines recommend the use of tyrosine kinase inhibitors (TKIs) as the first-line therapeutic agent for patients with recurrent or metastatic kidney cancer. Additionally, there is limited data on the combination of systemic treatment and SABR for extensive metastatic RCC due to concerns about high toxicity. Proton therapy offers a promising treatment option as it emits energy at a specific depth, generating high target doses while minimizing damage to normal tissue. This allows for precise treatment of various tumor lesions. In this case report, we describe a high-risk 65-year-old male with extensive pleural and thoracic lymph node metastases and 2 bone metastases of clear cell renal cancer. While the targeted therapy and immunotherapy effectively treated the bone metastases, it was not effective in treating the chest metastases, including the pleural and lymph node metastases. Thus, the patient received full-coverage radiotherapy with photon for primary renal tumor and intensity-modulated proton therapy (IMPT) for thoracic metastases. The patient showed no evidence of disease for 1 year after the initial radiotherapy, and no severe SABR-related adverse effects were observed until now. The combination of targeted therapy and immunotherapy with full-coverage radiotherapy may be a promising treatment option for selected patients with extensive metastatic renal cancer, especially as proton therapy allows for more precise control of the beam and minimal damage to normal tissue. This case has motivated us to investigate the potential advantages of administering proton therapy concurrently with systemic therapy in the management of metastatic renal cell carcinoma patients. [ABSTRACT FROM AUTHOR]