SRT versus ART
While urgently awaited prospective randomized trials are underway to compare SRT and ART, several retrospective/indirect analyses into that question have been conducted. In a first report, 75 patients receiving ART at a median dose of 60 Gy were compared with 71 patients who had SRT at 70 Gy. Although 49% of the SRT patients and only 3% of the ART patients received adjuvant HT, the 5-year post-RT bNED rate was 66 versus 88% in favor of ART (p < 0.0008). Both Kaplan–Meier curves plateaued at the respective levels for over 4 years.
In a case–control analysis, 361 ART patients were compared with 722 non-ART patients, who were selected to match the cases by treatment period, age, pre-RP PSA, tumor stage, Gleason score and surgical margin status. While 10-year bNED after ART was significantly improved over non-ART (63 vs 45%), there was no difference in overall survival. In the same study, an SRT cohort of 856 patients who were treated after biochemical relapse (median PSA: 0.8 ng/ml) was followed up over a median of 5.9 years. A total of 63% of the SRT patients achieved an undetectable PSA after SRT and the hazard ratio for local recurrence after SRT was 0.13. However, similar to ART, no improved overall survival could be shown after SRT.
A straight retrospective comparison with salvage (76 Gy) and adjuvant (74 Gy) IMRT patients (n = 89 in both arms) who were matched for personal and tumor characteristics, resulted in a significant bNED advantage from ART calculated either from the time of RP or from the end of RT (90 vs 65% 3 years post-RT and 91 vs 84% post-RP). However, the pre-RT PSA was a key parameter for that difference: a subcohort (n = 38) receiving early SRT (at PSA <0.5 ng/ml) had a 3-year post-RT bNED rate of 86%, quite different from the delayed SRT group, who had 46% bNED, but very similar to ART patients. Therefore, while overall Kaplan–Meier rates of bNED calculated in either mode suggested a benefit from ART, it was concluded that ART and early SRT did not yield significantly different results. This study included tumor stages from pT2 to pT4 and approximately 30% of the patients had received HT.
A similar case-matched study was restricted to pT3–4 N0 patients. A total of 96 men were included in either treatment arm, with none receiving HT. Even excluding patients with a pre-SRT PSA above 2 ng/ml from the analysis (thus, leaving the median at 0.7 ng/ml), a statistically significant bNED advantage from ART was seen, both calculated from the date of RP and from the end of RT.
The largest retrospective case-matching study to evaluate ART versus early SRT only included pT3 N0 R0/R1 patients. HT was excluded. A total of 390 out of 500 observation-plus-early-SRT patients (median pre-SRT PSA was 0.2 ng/ml) were propensity matched with 390 ART patients. At 2 and 5 years after surgery, bNED rates were 91 and 78%, respectively, for ART versus 93 and 82%, respectively, after SRT. Subgroup analyses also did not yield significant differences for the two approaches. It was concluded that early SRT does not impair PC control but clearly helps to reduce overtreatment, which is a major issue in ART.
This last aspect has also been emphasized in an approach to model the outcome of STR and ART under consideration of quality of life; results from the three randomized ART trials[33,51,53,54] and one large SRT study were used to estimate and validate transition probabilities during the course of disease. Psychological distress and the major normal tissue complications, namely erectile dysfunction, bowel dysfunction, urinary obstruction and urinary incontinence, were accounted for in utility calculations. In summary, ART was predicted to show a slightly better outcome than observation plus SRT in terms of bNED, metastasis-free and overall survival. However, within the limits of accuracy of modeling, when side effects were included into decision-making, a preference for (early) SRT resulted for patients who would comply with the tight surveillance routine; but if 50% of the patients in the observation arm fail to receive SRT, ART is the favorable treatment. According to one report, only a third of 303 patients with post-RP recurrence received salvage treatment within a mean of 12 months. In a study covering two decades, 340 (49%) out of 697 patients continued sole observation after biochemical relapse: "before 1995, approximately 70% of recurrent patients remained untreated 3 years after biochemical recurrence while after 2000 more then half were treated within 3 years".
When comparing ART with SRT, it must be kept in mind that a considerable number of ART patients would be relapse-free even without RT. The proportion is likely to be the same as in the observation arms of the three randomized studies (see the 'Adjuvant RT' section),[33,51,54] which was approximately 50% after 5 years. Further follow-up of the survival end points may help to identify patients who would have had a benefit from ART.
Future Oncol. 2013;9(5):669-679. © 2013 Future Medicine Ltd.