Overall survival benefit of androgen suppression in addition to dose-escalated external beam radiotherapy for high-risk prostate cancer: Nationwide real-world data indicates a shift in men that benefit

Objective: To evaluate the real-world added value of androgen deprivation therapy (ADT) in addition to external beam radiotherapy (EBRT) in men with high-risk non-metastatic prostate cancer, in view of advances in radiotherapy and diagnostics. Methods: All Dutch men diagnosed with high-risk non-metastatic prostate cancer (defined as: ≥cT2c-T3b N0M0, PSA ≥20–50 ng/ml, and/or Gleason score ≥8 (International Society of Urological Pathology [ISUP] grade ≥4)) from 2009 through 2019 and treated with EBRT with or without ADT were identified in the population-based Netherlands Cancer Registry. Propensity scores were used to match (1:1) men that received ADT to men that did not receive ADT. Subsequently, OS was compared. Analyses were also stratified by number of high-risk features, 1 (either ≥cT2c, PSA >20 ng/ml or Gleason score ≥8) versus ≥2 (out of ≥cT2c, PSA >20 ng/ml and Gleason score ≥8). Results: A total of 14,773 men with high-risk non-metastatic prostate cancer were identified, 3,958 (27%) of which received EBRT alone. After matching, 3,427 men remained in both groups and baseline characteristics were well-balanced. After a median follow-up of 92 months, OS was better in men treated with EBRT and ADT compared to men treated with EBRT alone (10-year OS: 66.4% versus 61.8%; HR 0.88 [95%CI: 0.80–0.96]). There was no statistically significant difference in OS in the subgroup of men with only 1 high-risk feature (10-year OS 67.7% versus 64.9%; HR 0.95 [95%CI: 0.85–1.07]). Conclusions: In a contemporary cohort of men treated for high-risk non-metastatic prostate cancer with EBRT, an OS benefit of adding ADT was only observed in men with at least 2 high-risk features. These results suggest that improvements in diagnostics and treatment in recent decades have resulted in a stage shift of men benefiting from the addition of ADT to EBRT

Cognitive performance and the hippocampus in patients with postoperative pituitary radiotherapy: A detailed dosimetric study

Context and objective: We showed previously that postoperative radiotherapy (RT) for nonfunctioning pituitary macroadenoma (NFA) is unlikely to have a major effect on cognition. However, a small effect could not be excluded. Radiation dosimetry offers the possibility to relate radiation exposure of brain areas of interest to cognitive performance, thereby detecting smaller effects potentially induced by RT. The hippocampus has a crucial role in memory and information processing and is known to be sensitive to radiotherapy. Here, we studied the effects of various pituitary RT techniques by relating detailed dosimetry of the hippocampus to cognitive performance. Design: Aspects of verbal memory and problem solving were assessed by using standardized neuropsychological test procedures that have been shown to be sensitive to the effects of brain surgery and radiation. We compared dosimetric data of 3 different RT techniques (3-fields, 4-fields and 5-fields technique) and a non-irradiated patient group. A reconstruction was made of the different radiation techniques used and the mean left and right hippocampi doses were calculated. Patients: 75 patients (61±10 year) underwent transsphenoidal surgery as primary treatment. Irradiated patients (n=30) were divided into 3 groups; 3-fields technique n=10; 4-fields technique n=15; 5-fields technique n=5. All patients received 45 gray (Gy), given in 25 fractions of 1.8 Gy. Cognitive performance data from the different irradiated patients groups and the non-irradiated patient group (n=45) were compared. Results: Mean (SD) cumulative dose for the left hippocampus irradiated with the 3-, 4-, and 5-fields techniques were respectively 13.82 (15.11), 18.46 (10.09), and 12.48 (12.41) Gy. Mean cumulative dose for the right hippocampus with the 3-, 4-, and 5-fields techniques were 15.55 (16.61), 22.27 (12.05), and 13.82 (14.48) Gy. No significant differences were found for the different RT techniques and the non-irradiated patients for cognitive tests, particularly memory and information processing which has its anatomical substrate in the hippocampus (Verbal memory, P=0.337). No radiation dose- cognitive response relationship was detected. Conclusion: Postopertive pituitary RT has no effect on cognitive performance involving the hippocampus in NFA patients. No dose response relationship could be established, confirming that these RT techniques and fractionated radiation dose regimens are safe with regard to cognition

Symptomatic Skeletal Events and the Use of Bone Health Agents in a Real-World Treated Metastatic Castration Resistant Prostate Cancer Population: Results From the CAPRI-Study in the Netherlands

Background: Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of symptomatic skeletal events (SSE). Bone health agents (BHA, ie bisphosphonates and denosumab) and new life-prolonging drugs (LPDs) can delay SSEs. The aim of this study is to investigate the use of BHAs in relation to SSEs in treated real-world mCRPC population. Patients and Methods: We included patients from the CAPRI registry who were treated with at least one LPD and diagnosed with bone metastases prior to the start of first LPD (LPD1). Outcomes were SSEs (external beam radiation therapy (EBRT) to the bone, orthopedic surgery, pathologic fracture or spinal cord compression) and SSE-free survival (SSE-FS) since LPD1. Results: One-thousand nine hundred and twenty-three patients were included with a median follow-up from LPD1 of 16.7 months. Fifty-two percent (n = 996) started BHA prior or within 4 weeks after the start of LPD1 (early BHA). In total, 41% experienced at least one SSE. SSE incidence rate was 0.29 per patient year for patients without BHA and 0.27 for patients with early BHA. Median SSE-FS from LPD1 was 12.9 months. SSE-FS was longer in patients who started BHA early versus patients without BHA (13.2 vs. 11.0 months, P =.001). Conclusion: In a real-world population we observed an undertreatment with BHAs, although patients with early BHA use had lower incidence rates of SSEs and longer SSE-FS. This finding was irrespective of type of SSE and presence of risk factors. In addition to LPD treatment, timely initiation of BHAs is recommended in bone metastatic CRPC-patients with both pain and/or opioid use and prior SSE

Third-line Life-prolonging Drug Treatment in a Real-world Metastatic Castration-resistant Prostate Cancer Population: Results from the Dutch Castration-resistant Prostate Cancer Registry

Third-line life-prolonging drugs (LPDs) might not be appropriate for all metastatic castration-resistant prostate cancer patients. We developed a prognostic model and identified a high-risk subgroup in which no meaningful benefit from third-line LPDs is derived in clinical practice