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.

Fig. 1

Ten-year prostate-specific antigen (PSA) relapse-free survival for low-risk patients was 84% and 70% for patients treated with ≥75.6 Gy and with lower doses, respectively (p = 0.04). RT = radiotherapy.

Fig. 2

Prostate-specific antigen (PSA) relapse-free survival for intermediate-risk patients according to dose. The 10-yr outcomes were 76% and 57% for patients treated with >81 Gy and with lower doses, respectively (p < 0.0001). RT = radiotherapy.

Fig. 3

Prostate-specific antigen (PSA) relapse-free survival for high-risk patients according to dose. The 10-yr outcomes were 55% and 41% for patients treated with >81 Gy and with lower doses, respectively (p < 0.0001). RT = radiotherapy.

Fig. 4

The 10-yr prostate-specific antigen (PSA) relapse-free survival for high-risk patients treated with and without androgen-deprivation therapy was 55% and 36%, respectively (p < 0.0001). NeoHT = neoadjuvant hormone therapy.

Fig. 5

Prostate-specific antigen (PSA) relapse–free survival according to the use of androgen-deprivation therapy (ADT). Use of a 6-mo course of ADT is significantly associated with improved biochemical tumor control. NeoHT = neoadjuvant hormone therapy.

Fig. 6

Nomogram for predicting biochemical tumor control at 5 and 10 yr after external-beam radiotherapy (RT) (concordance index: 0.67). HT = 6 mo neoadjuvant and concurrent hormone therapy; PSA = prostate-specific antigen.

Fig. 7

Competing-risks analysis demonstrating the likelihood of prostate cancer (PCa) mortality for low-, intermediate-, and high-risk patients (p < 0.0001).