Richard G. Stock

Objectives: The objective of this study is to propose a novel method of determining the nadir PSA (nPSA) for men with prostate cancer treated by partial gland ablation (PGA).Materials and Methods: Two cohorts of men were analyzed to develop a formula for the nPSA in men undergoing PGA. First, 123 men with a suspicion of prostate cancer underwent transperineal mapping biopsy (TPMB) and found to have benign pathology. Their prostate‐specific antigen (PSA) was compared to the prostate volume using curve estimation regression analysis. Second, the contribution of PSA from an ablated region was determined by using a surrogate of 545 men who had whole‐gland brachytherapy followed by prostate biopsy. Biopsy results were compared to radiation dose (calculated as the biological equivalent dose) levels in men who were free from biochemical failure. The nPSA was then calculated by using the PSA density (PSAD) for the untreated volume plus the PSA from the post‐brachytherapy patients.Results: The PSAD with the highest R² (0.80, p < 0.001) for the 123 men who had TPMB and a negative biopsy was 0.12 ng/mL². In the brachytherapy patients, five 20 Gy dose groups were analyzed from ≤140 to ≥220 Gy, which demonstrated a progressive decrease in the positive biopsy rate to 1.5% at the highest dose (p = 0.036). PSA was 2.Conclusion: A method for determining the nPSA following PGA using brachytherapy was developed. The formula relies on complete ablation of the treated volume, which resulted in no PSA contribution from that component. Other forms of ablative energy should yield similar results. Further clinical validation of this concept is warranted.

The breakthrough of a limited number of clones while on immune checkpoint inhibitors (ICIs), known as oligoprogression, has been previously described. The benefit of ablative radiation therapy (RT) directed at these clones, as opposed to changing systemic therapy, is unclear. We analyzed 30 patients with advanced solid tumors, the majority of whom (23/30, 86.7%) had either hepatocellular or urothelial carcinoma, who experienced oligoprogression on ICIs and were referred for RT. In this study, oligoprogression was defined as having experienced progression at three or fewer metastatic sites outside of the brain after achieving at least stable disease on ICIs for a minimum of three months. The median time to oligoprogression was 11.1 months from the initiation of immunotherapy. 24 patients had one oligoprogressive lesion and six had two. The median radiation dose delivered was 4650 cGy in a median of five fractions. The median progression-free survival (PFS) after RT was 7.1 months, and the time to oligoprogression was not a significant predictor of PFS2. 26 patients continued on ICIs after RT. While 17 patients subsequently progressed, 15 did so at three or fewer metastatic sites and could have theoretically stood to benefit from an additional course of salvage RT to further extend the lifespan of their ICIs. Overall survival at 6, 12, and 24 months was 100.0%, 96.3%, and 82.8%, respectively. These results suggest that RT may provide a PFS benefit and extend the lifespan of ICIs in patients who experience oligoprogression. Regardless of PFS, however, overall survival in this population appears to be excellent.

Objectives: To report the long‐term results of prostate brachytherapy followed by external beam radiotherapy ( EBRT ) in men with a positive seminal vesicle biopsy (+ SVB ). Patients and Methods: In all, 1081 men with localised prostate cancer were treated with permanent brachytherapy, of which 615 had staging SVB and 53 (9.4%) were positive. Higher stage, Gleason score and PSA level were associated with a + SVB ( P < 0.001). Patients with + SVB and negative laparoscopic pelvic lymph node dissection, bone and CT scans had 3 months of androgen‐deprivation therapy ( ADT ) followed by ¹⁰³ Pd implant to the prostate (dose 100 Gy) and proximal SV s, and 2 months later 45 Gy EBRT . ADT was continued for a median of 6 months (total ADT 9 months). The mean (range) follow‐up was 9 (5–22) years. Results: Biochemical freedom from failure (computed by the Phoenix definition), freedom from metastasis, and cause‐specific survival ( CSS ) for patients with a negative SVB (–SVB) vs + SVB at 15 years, was 76.3% vs 60.6% ( P = 0.001), 95.4% vs 78.2% ( P < 0.001), and 95% vs 70.4% ( P < 0.001), respectively. Prostate cancer death occurred in 45 of 590 (7.6%) men with a – SVB vs eight of 25 (32%) with a + SVB ( odds ratio 5.7, 95% confidence interval 2.35–13.9, P < 0.001). Cox proportion hazard rates (HRs) demonstrated Gleason score ( P < 0.001, HR 1.9), stage ( P = 0.010, HR 1.42), RT dose ( P = 0.013, HR 0.991), and + SVB ( P = 0.001, HR 4.48), as significantly associated with CSS . Conclusions: Men with a + SVB have inferior CSS compared to those with a − SVB . However, a strategy that included a SVB in high‐risk patients and implantation of the SVs in men undergoing combined therapy still yields favourable long‐term results.

Objectives: To determine which patient and treatment‐related factors are associated with increased American Urological Association symptom score ( AUASS ) in men who presented with minimal symptoms before treatment for prostate cancer by permanent seed implantation. Patients and Methods: Of 1842 men with a minimum follow‐up of 5 years (mean 9.4), 1110 (60.3%) had an initial AUASS of 0–7 and were treated with brachytherapy ( BT ) alone ( n = 491) or BT with neoadjuvant hormone therapy ( NHT ) and/or external beam radiation therapy ( EBRT , n = 619). The median prostate volume was 37 mL . Data were prospectively collected on comorbidities. Initial AUASS was compared to last using a Student's t ‐test (two‐tailed). Freedom from increasing from minimal to moderate or severe symptoms was determined by the Kaplan–Meier method with comparisons by log‐rank and Cox hazard rates ( HR s). Results: The change from pre‐treatment score for the minimal, moderate and severe symptom groups was: 3.6–7.3 ( P < 0.001), 11.6–11.3 ( P = 0.426), and 24.1–16.9 ( P < 0.001). For those with minimal symptoms the 10‐ and 15‐year estimates for freedom from worse symptoms were 72.9% and 39.1%, respectively. Cox HR s were significant for EBRT boost ( HR 1.45, P = 0.004), RT dose >200 Gy ₂ ( HR 1.25, P = 0.024), hypertension ( HR 1.37, P = 0.006), and alcohol use ( HR 1.46, P = 0.001). Conclusion: A substantial number of men with initial low AUASS treated by BT experience worsening urinary symptoms with long‐term follow‐up. Use of EBRT , RT dose, hypertension and alcohol use are risk factors for an increase in urinary symptom score.

Whether due to perceived poorer outcomes with radiation therapy or concern for higher relapse rates attributable to longer life expectancy, there is a bias to recommend radical prostatectomy for younger men with newly diagnosed prostate cancer (PCa). We sought to evaluate the oncological and function outcomes of young men treated with low dose rate brachytherapy (LDR) for PCa.