Several studies have demonstrated low rates of local recurrence with brachytherapy-based accelerated partial breast irradiation (APBI). However, long-term outcomes on toxicity (e.g. telangiectasia) and cosmesis remain a major concern. The purpose of this study is to investigate the dosimetric feasibility of using targeted non-toxic radiosensitizing gold nanoparticles (GNPs) for localized dose enhancement to the planning target volume (PTV) during electronic brachytherapy APBI while reducing normal tissue toxicity. We propose to incorporate GNPs into a micrometer-thick polymer film on the surface of routinely used lumpectomy balloon applicators and provide subsequent treatment using a 50 kVp Xoft device. An experimentally determined diffusion coefficient was used to determine space-time customizable distribution of GNPs for feasible in-vivo concentrations of 7 mg/g and 43 mg/g. An analytical approach from previously published work was employed to estimate the dose enhancement due to GNPs as a function of distance up to 1 cm from the lumpectomy cavity surface. Clinically significant dose enhancement values of at least 1.2, due to 2 nm GNPs, were found at 1 cm away from the lumpectomy cavity wall when using electronic brachytherapy APBI. Higher customizable dose enhancement was also achieved at other distances as a function of nanoparticle size. Our preliminary results suggest that significant dose enhancement can be achieved to residual tumor cells targeted with GNPs during APBI with electronic brachytherapy.

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. ⁶⁸Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, ⁶⁸Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of ⁶⁸Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. ⁶⁸Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4–5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, ⁶⁸Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4–5 lesions, ⁶⁸Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of ⁶⁸Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and ⁶⁸Ga-PSMA-11 PET/CT.

Background: Management of localised prostate cancer (PCa) remains controversial in the era of prostate-specific antigen (PSA) testing. This study aims to describe the natural history of men with PCa being followed up expectantly to evaluate disease mortality. Methods: After exclusion, clinical data of 204 patients retrieved from a prospective large PCa registry were reviewed. Competing risk analysis were performed using the Fine-Gray model. Results: The median age was 73 years old with a median follow up of 12.5 years. The median PSA was 8.85 ng/mL and the risk stratification were as follows: low (47.0%), intermediate (31.4%), and high risk (21.6%). There were 19 PCa (9.3%) and 84 non-PCa deaths (41.2%), with overall mortality at 50.5%. Multivariate analysis showed patients with high PSA values [subdistribution hazard ratio (sdHR) 7.13], poorer prostate cancer grade groups (PCGG) (sdHR 16.349), and therefore higher European Association of Urology risk group (sdHR 11.42) had greatly elevated prostate cancer mortality (PCM). Older patients greater than 75 years of age (sdHR 4.52) and high Charlson Comorbidity Index (CCI ≥6) scores had higher non-prostate cancer mortality (NPCM) (sdHR 7.87). Subgroup analysis of the high-risk group showed having a lower CCI score (≤3) had a greater risk of PCM than NPCM (sdHR 4.31 vs. 0.22) while the converse is observed for higher CCI scores (1.12 vs. 5.52). Conclusions: Overall PCM remains low in elderly men with conservatively treated PCa. Age and poorer CCI predict NPCM while PSA and PCGG predict PCM. In high-risk PCa group, CCI is a useful tool to determine which patients will benefit from radical treatment.