198 men fulfilled the inclusion criteria and were included in the study. Their characteristics are detailed in Table . Median age was 67 years (49-80). 69 patients were treated with the free seeds technique and 129 with the FIRST technique. The majority of the patients were classified in the low risk group according to D'Amico et al. classification (71.2%), and the others in the intermediate group.
The median follow-up was 63.9 months (range 36 - 119.4), 88.4 months (range 36.3 - 95.6) for the former implantation technique and 52.9 months (range 36 - 81.9) for FIRST.
A total of 2,219 PSA values were recorded, with a median number of 10.5 per patient (range: 3 - 24). Figure shows distribution of PSA values at each visit.
A and B. Distribution of PSA values per visit for patients who had bounce or relapsed. Figure 1A for bounce and B represents relapse.
At the first visit, scheduled 6 weeks after the brachytherapy (median 6.4 weeks, range 4.1 - 9.7), 20% of the patients had a PSA increase from its initial value (median increase: 0.83 ng/ml, range: 0.1 - 5.2). This value was not taken into account in bounce identification as it may have been altered by implantation and prostate edema.
At the time of analysis, 80.3% of the patients had achieved a nadir < 0.5 ng/ml.
Seventy one patients (35.9%) experienced at least one bounce defined by a PSA increase of at least 0.2 ng/ml followed by a spontaneous decrease to or below pre-bounce level. Ten patients experienced 2 bounces and one patient experienced 3 bounces. The respective proportion of bounces defined as a PSA increase with a threshold of 0.1, 0.4 and 2 ng/ml followed by a decrease to or below pre-bounce level were 48.5, 25.8 and 4.5% respectively. Characteristics of the bounces are presented in Table .
PSA bounce characteristics according to bounce definitions
Median time to onset was 17 months (3.6-50.2), and 56.3% of the bounces occurred between 12 to 24 months after the brachytherapy. After 30 months, bounces were rare (8.5%).
The median bounce duration was 13.6 months (range: 4.0-44.9), and 75% were limited to 20 months. 18.3% lasted over 2 years. The median increasing part duration of the bounces, which is the most agonizing, was 6.4 months (1.3-23), and was limited in 75% of the bounces to 11 months.
The median magnitude was 0.6 ng/ml (0.2-5.1). It was lower than 1 ng/ml in 72% of the cases, but higher than 2 ng/ml in 12.5% of the bounces (9 patients).
Predictive factors for bounces
In univariate analysis, younger age was significantly associated with a higher probability of a bounce occurrence (p = 0.003). There was also a trend for higher PSA value at 6 weeks (p = 0.053) (Table and Figure ). Dosimetric and clinical factors as well as initial PSA value and Gleason score were not associated with bounce.
Predictive factors for bounce (univariate and multivariate analysis)
6 week PSA value according to patients outcome: BF or bounce.
In multivariate analysis, younger age (p = 0.0016, HR = 0.93, CI95%: 0.888-0.972) and higher PSA value at 6 weeks (p = 0.0197, HR = 1.17, CI95%: 1.025-1.327) were significantly associated with a higher probability of a bounce (Table ). Patients with PSA bounce were significantly younger (median age 66 years (range: 51-79) vs. 69 years (49-80)) and had a higher PSA value at 6 weeks (median 5.2 ng/ml (0.6-11.3) vs. 4.3 (0.1-11.6)).
Predictive factors for true recurrence (univariate analysis)
Strictly applying the RTOG-ASTRO Phoenix consensus definition, 21 patients (10.6%) were considered to have a biochemical relapse (nadir +2 ng/ml), resulting in a 4 year relapse free survival (RFS) of 92% (CI95% = 87-95). Six patients had salvage hormonal therapy (3 with positive biopsies), including 2 who did not meet the BF criteria (nadir +2 ng/ml).
In 9 cases, the PSA raise overcame the threshold of 2 ng/ml, but was followed by a spontaneous decrease to or below pre-bounce level fulfilling bounce definition. Thus, the "true recurrence rate" (true BF or salvage treatment) was 7.1% (21 BF + 2 salvage therapy - 9 bounces = 14 pts) and a 4 year RFS of 95% (CI95% = 91-97).
Predictive factors for biochemical failures
"True recurrences" (definition above) occurred respectively in 5 pts belonging to the intermediate risk group (8.8%) and in 9 pts to the low risk group (7.1%) (p = 0.686).
In univariate analysis, no factor was found being predictive of true relapse. Results are shown in Table .
There was a better true biochemical relapse free survival in patients who experienced a bounce (true relapse free survival rate at 4 years: 100% vs 92%, logrank test: p = 0.0066).
Of the 71 patients who experienced a bounce, only one subsequently had a true biochemical relapse; he belonged to the intermediate prognosis group. Hence, none of the patients in the low risk prognosis group who had a bounce experienced a true biochemical relapse. Moreover, none of the patients who experienced a bounce > 2 ng/ml experienced a true biochemical recurrence.
Biochemical failures vs. bounce
One patient experienced a bounce followed by a true biochemical relapse. He was considered as bounce patient here. Table presents results of comparison between the 71 bounces and the 14 true relapses.
Comparison between true biochemical relapse vs bounce
Median PSADT was 11.5 months for the 71 patients who experienced a bounce (range: 1.0-70.2) and 12.0 months for the 14 patients with a true recurrence without bounce (range: 3.9-49.5). The median PSA velocity was estimated at 0.11 ng/ml/month for patients experiencing bounce (range: 0.01-0.85) and 0.12 ng/ml/month for patients with true relapse (range: 0.03-0.58). There was no difference between groups.
The median nadir before the rise was 1.38 ng/ml (range: 0.02-6.6) for bounce patients and 1.00 (range: 0.04-3.04) for true relapse patients (p = 0.25).
Bounces occurred significantly earlier than true BF (17 months vs. 44 months, p < .0001). Furthermore, the level of nadir + 0.2 ng/ml was reached significantly later in true BF cases than in bounce: 27.8 versus 17 months (p < 0.0001)