Postprostatectomy Radiation Therapy

An Evidence-based Review

Mark V Mishra; Colin E Champ; Robert B Den; Eli D Scher; Xinglei Shen; Edouard J Trabulsi; Costas D Lallas; Karen E Knudsen; Adam P Dicker; Timothy N Showalter

Disclosures

Future Oncol. 2011;7(12):1429-1440. 

In This Article

Treatment Morbidity

Treatment Toxicity

All three randomized clinical trials discussed above also included an analysis of gastrointestinal (GI) or genitourinary (GU) toxicity in the two cohorts (ART vs observation). However, it should be noted that the EORTC and SWOG trials used 2D-based treatment planning, which did not allow for significant normal tissue sparing. This is in contrast to modern 3D-based planning treatment delivery using sophisticated intensity-modulated RT (IMRT) to minimize RT dose to the rectum and bladder.

In the SWOG 8794 study,[5] 3.3% of men in the postoperative RT group developed proctitis or rectal bleeding compared with 0% of men in the observation group (p = 0.002). The incidence of urethral strictures was also significantly more common in the immediate postoperative RT group (17.8 vs 9.5%; relative risk: 1.9; p = 0.02). Total urinary incontinence occurred in 6.5% of men in the RT group compared with 2.8% of men in the observation group (relative risk: 2.3; p = 0.11).

In the EORTC trial, there was no statistically significant difference in high-grade (grade 3 or higher) toxicity between the ART and observation group.[4] The cumulative incidence of late grade 3 events was 4.3 versus 2.6% (p = 0.0726) by 5 years for men treated with ART versus initial observation, respectively. Altogether, the total number of late grade 2 and 3 toxicity events combined were more prominent in the ART group (p = 0.0005). Unlike the SWOG trial, total urinary incontinence was not assessed in EORTC study. However, an initial interim analysis that was performed showed no significant difference in urinary incontinence between the two treatment arms.

In the German study, which utilized 3D-based radiation treatment planning, the incidence of late grade 3 or higher toxicity was only 0.3% after a median follow-up of 4.5 years.[7] One patient developed a urethral stricture in the observation arm, compared with two patients in the ART arm. Urinary incontinence was not assessed in this trial.

Quality of Life

The SWOG 8794 trial also collected patient-reported treatment-related adverse effects.[12] Health-related quality-of-life (HRQOL) data were collected prior to randomization, at 6 weeks, at 6 months, and annually for 5 years. A total of 217 of 425 patients enrolled in the trial participated in the HRQOL study. The prespecified outcomes of the study were: bowel function tenderness, urinary frequency and rectal dysfunction, as well as measures of physical and emotional function. Patients randomized to ART reported worse bowel and urinary function for about 2 years following ART. However, there were no differences in bowel function present at 5 years following treatment. There were no differences in erectile dysfunction between the two cohorts. Notably, while composite HRQOL was initially worse in the ART group, with longer follow-up it was found to be superior in the ART versus observation group (p = 0.004).

While the EORTC and German trials did not assess HRQOL data, there have been other clinical trials that have prospectively assessed this issue. In one prospective study of HRQOL factors for patients treated with postprostatectomy RT, HRQOL following RT was only mildly changed compared with prior to treatment.[13] Additionally, an interesting finding from for this analysis was that patients with a longer time interval between RP and initiation of RT reported greater bother due to urinary incontinence than those with a shorter time between RP and RT (p = 0.02).

Physician Perceptions Of Treatment Morbidity

Commonly held physician beliefs about the impact of the timing between initiation of RT following RP upon the postoperative recovery of urinary and sexual function likely influence utilization rates of ART. Although leaders who oppose the routine use of ART postulate that RT initiated within 2–4 months following RP may 'stall' recovery of urinary continence and erectile function. Many physicians also assume similar rates of erectile dysfunction with ART as with definitive RT for PC treatment,[14] despite the lower RT dose used for ART. For example, although the randomized trials included ART initiated 3–4 months after RP,[4,5,7] a national survey revealed that 69% of clinicians instead prefer to delay ART until beyond 4 months following RP.[15] Direct data to inform these considerations are lacking, particularly regarding sexual function. Interestingly, a 2010 report suggests a distinct cohort of men lose erectile function between 3 and 6 months after RP alone,[16] an observation that may obscure the interpretation of published data regarding impact of ART on erectile function. In a recent systematic review and analysis of late toxicity data from 13 published SRT reports, our group found that SRT dose was associated with an increased risk of grade ≥3 GI and GU toxicity, and that timing of RT did not influence risk of toxicity.[17] Thus, the commonly-accepted belief that ART within 4 months after RP will stall recovery of urinary and sexual function has limited clinicians' utilization of ART for PC patients, with limited data to directly support this notion.

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