Dose Escalation for Prostate Cancer Radiotherapy: Predictors of Long-Term Biochemical Tumor Control and Distant Metastases–Free Survival Outcomes

Abstract

Background Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. Objective Identify predictors of biochemical tumor control and distant metastases–free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. Design, setting, and participants This retrospective analysis comprised 2551 patients with clinical stages T1–T3 PCa. Median follow-up was 8 yr, extending >20 yr. Intervention Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. Measurements A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Results and limitations Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels <70.2 Gy and 70.2–79.2 Gy were associated with 2.3-and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse– free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes. Conclusions Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high-risk patients; however, an overall survival advantage was not observed.

A Phase II Study of Salvage High-Dose-Rate Brachytherapy for the Treatment of Locally Recurrent Prostate Cancer after Definitive External Beam Radiotherapy

“…Of the three patients who developed Grade 3 urinary toxicity, two were characterized at baseline as having Grade 2 symptoms, and one patient was classified as having Grade 1 symptoms at baseline. The median IPSS at baseline was 6 (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], and the median IPSS at last followup was 12 (range, 1-30). Resolution of an elevated IPSS was seen in 41% of patients (returned within 2 points of baseline) within a median time of 4.5 months.…”

“…High-dose intensity-modulated radiotherapy (IMRT) has proven to be an effective treatment for localized prostate cancer (1)(2)(3)(4)(5)(6). In the case of local recurrence, salvage options are limited for these patients.…”

Therapeutic outcomes of neoadjuvant and concurrent androgen‐deprivation therapy and intensity‐modulated radiation therapy with gold marker implantation for intermediate‐risk and high‐risk prostate cancer

“…[1][2][3][4][5][6][7][8][9] Three-dimensional conformal radiation therapy, which was introduced in the 1990s, allows for safe delivery of higher radiation doses to the target area. Despite the use of more conformal treatment, the dose received by the rectum is still significant, which results in adverse events, such as hemorrhage.…”

Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy

“…EBRT dose escalation has led to further improvement of these results 1,3 . However, depending on tumour characteristics, PSA-parameters and use of androgen deprivation therapy (ADT), biochemical recurrences can still occur in 30-50% of patients after 5-10-years 1,3 . Over 80% of patients can harbour a prostate-only recurrence 4 .…”