Variation in the Use of Postoperative Radiotherapy Among High-risk Patients Following Radical Prostatectomy

TM Morgan; SR Hawken; KR Ghani; DC Miller; FY Feng; SM Linsell; JA Salisz; Y Gao; JE Montie; ML Cher

Disclosures

Prostate Cancer Prostatic Dis. 2016;19(2):216-221. 

In This Article

Results

Patient Characteristics and Association With ART

Among 2337 consecutive patients undergoing RP during the study period, 668 (28.6%) met the inclusion criteria. These patients were managed at 23 urology practices, and Figure 1 displays the flow of post-RP treatment decisions. The median patient age was 64 years (interquartile range=58–68 years) and the median pre-treatment PSA was 6.12 ng ml−1 (interquartile range=4.50–8.94 ng ml−1). Among the entire cohort, 227 (34.0%) were stage pT2, 322 (48.2%) were pT3a, 118 (17.7%) were ≥pT3b and 412 (62.1%) had positive surgical margins ( Table 1 ). Patients were followed for a median of 15 months post RP (interquartile range=11–21 months), and 178 (28.9%) reached a post-nadir PSA ≥0.1 ng ml−1 (Figure 1). A total of 52 patients (7.8%) received ART, 56 (8.4%) underwent SRT and 5 (0.8%) underwent salvage androgen deprivation, whereas 555 patients (83.1%) have received no additional therapy to date. Only 2/438 patients (0.5%) with all post-nadir PSA levels <0.1 ng ml−1 received radiotherapy after >1 year of follow-up. The clinicopathologic characteristics of the entire cohort, stratified by ART administration, are presented in Table 1 . Patients that received ART tended to be younger (P=0.027) and were found to have more aggressive pathological tumor features, including higher stage (P<0.001) and Gleason grade (P=0.009). ART use also varied by practice size (P=0.01), with the smallest and largest size practices utilizing ART more frequently. Pre-treatment PSA and nodal status were not significantly associated with ART, although there did appear to be trends towards greater ART utilization in patients with higher pre-treatment PSA levels and patients with node-positive disease.

Figure 1.

Treatment decisions for patients at high risk of recurrence following radical prostatectomy (RP). Flow chart of the post-prostatectomy treatment decisions for patients with pT3a disease or higher and/or positive surgical margins.

Although there was no association between surgical margin status and ART use across the cohort as a whole, we evaluated three distinct combinations of pathological stage and margin status to determine the incremental effect of each local recurrence risk factor on ART administration. Only 4/227 patients (1.8%) with pT2 margin-positive disease received ART, whereas 20/253 (7.9%) with pT3 margin-negative and 28/188 (14.9%) with pT3 margin-positive tumors received ART (P<0.001, Supplementary Table 2).

Data Validation

For the 144 men in the study cohort with BCBSM insurance, there was excellent concordance κ=0.98 (95% CI: 0.94–1.0) between the registry and claims data (Supplementary Table 3).

Variation in use of ART and SRT

ART use varied widely by MUSIC practice, with adjusted site-specific rates ranging from 0 to 67% (P<0.001, Figure 2). The adjusted mean probability of ART across the entire cohort was 8.2% (95% CI: 7.2–9.1%). Among patients not receiving ART, a total of 178 reached a post-nadir PSA ≥0.1 ng ml−1 with 54 (30.3%) undergoing subsequent SRT and 4 (2.2%) receiving salvage androgen deprivation. Again, rates of SRT administration varied significantly by practice, with adjusted rates ranging from 0% to 67% at the 14 evaluable practices (P=0.046, Figure 3). The adjusted mean probability of SRT among these patients was 31.4% (95% CI: 28.1–34.7%). Furthermore, as shown in Figure 4, adjusted practice-level rates of ART and SRT administration were highly correlated, with practices that more frequently administered ART also more commonly administering SRT to patients with a detectable PSA ≥0.1 ng ml−1 (Pearson's r=0.73, P=0.003).

Figure 2.

Adjusted likelihood of adjuvant radiation therapy administration for men with pT3 or greater disease and/or positive surgical margins, stratified by MUSIC practice. Rates were adjusted for patient age, pathologic stage, Gleason grade and preoperative PSA. The overall adjusted probability was 8.2% (95% CI: 7.2–9.1), and there was significant variation across practice sites (P<0.001). ART, adjuvant radiotherapy; CI, confidence interval; MUSIC, Michigan Urological Surgery Improvement Collaborative.

Figure 3.

Adjusted likelihood of salvage radiation therapy administration for men not receiving ART and with a rising PSA ≥0.1 ng ml−1, stratified by MUSIC practice. Rates were adjusted for patient age, pathologic stage, Gleason grade and preoperative PSA. Only practices with at least four eligible patients were included. The overall rate was 31.4% (95% CI: 28.1–34.7) and there was significant variation across practice sites (P=0.046). ART, adjuvant radiotherapy; CI, confidence interval; MUSIC, Michigan Urological Surgery Improvement Collaborative.

Figure 4.

Practice-level rates of salvage versus adjuvant radiation therapy (XRT) administration. There was a significant, positive correlation between rates of ART and SRT administration across practices (r=0.73, P=0.003). ART, adjuvant radiotherapy; SRT, salvage radiotherapy.

Timing of SRT Administration

Among patients who developed a detectable post-nadir PSA, salvage therapies were initiated at variable PSA levels (Figure 5). SRT was administered to 17/90 patients (18.9%) with a PSA between 0.1 and 0.19 ng ml−1, 25/50 (50.0%) between 0.2 and 0.49 ng ml−1, 7/18 (38.9%) between 0.5 and 0.99 ng ml−1 and 5/20 (25.0%) with a PSA ≥1.0 ng ml−1. Of the 88 patients with a PSA recurrence ≥0.2 ng ml−1, 38 (43.2%) progressed to a PSA ≥0.5 ng ml−1 and 20 (22.7%) to a PSA ≥1.0 ng ml−1 without receiving prior SRT.

Figure 5.

Timing of salvage therapy following radical prostatectomy (RP). Timing of salvage treatments according to maximum post-RP PSA for the 178 patients with a PSA ≥0.1 ng ml−1 after reaching a nadir PSA ≤0.1 ng ml−1 within 6 months after surgery. ADT, androgen deprivation therapy; XRT, radiation therapy.

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