Adjuvant and Salvage Radiotherapy after Radical Prostatectomy

Abstract

Background: Following radical prostatectomy, between 15 and 60% of all patients with pT3 prostate cancer experience persistence or increasing levels of prostate-specific antigen (PSA) as a sign of tumor persistence or progression within 5 years. Retrospective studies have shown a rate of 35–55% of positive biopsies from the vesicourethral anastomosis in this situation. Best treatment for these disease conditions is under debate, current strategies include adjuvant radiotherapy (RT), ‘wait-and-see‘ and salvage RT or hormone therapy for increasing PSA. Results: A number of retrospective studies have shown an increased rate of local control and ‘freedom from treatment failure‘ following adjuvant RT with doses in the range of 50–60 Gy. However, no survival benefit could be demonstrated by now. Results of three major phase III studies are pending. In case of persisting or increasing PSA levels following radical prostatectomy, 30–70% of these patients will reach an undetectable PSA level after conformal RT with total doses of 60–70 Gy, which will stay undetectable or at least stable within the next 2–5 years in about 50% and therefore offering a chance of cure. When starting RT, PSA should be as low as possible (<2 ng/ml). With higher PSA levels the chance of achieving an undetectable PSA again decreases below 35%. High Gleason scores of 8–10, seminal vesicle involvement and a short PSA doubling time are adverse prognostic factors. Severe late side effects of conformal RT are infrequent (<3%). In contrast, hormonal treatment is of palliative nature in the long run, with a median time to development of metastases of 4–7 years, and can be offered to patients with progressive disease after RT. Conclusions: Adjuvant RT following radical prostatectomy for pT3 prostate cancer offers higher local control rates and an increase in ‘freedom from treatment failure‘, but no prolongation of survival has yet been shown. In the situation of increasing PSA levels after radical prostatectomy, salvage RT seems to offer a chance of cure in selected patients, although it is difficult to draw firm conclusions because of generally too short follow-up times.

The Value of PSA Measurements at 30 Gy, 50 Gy and 60 Gy for Dose Limitation in Patients with Radiotherapy for PSA Increase after Radical Prostatectomy

“…In these patients the total dose could be restricted to 50-60 Gy. This would be important, as a dose of 50-60 Gy following radical prostatectomy can be given with 3-D-treatment planning with a rate of less than 1% of grade III or IV late side effects [8]. Unfortunately, up to now the identification of these patients is not supported by data from the literature.…”

“…Radiotherapy of patients with PSA increase following radical prostatectomy without histologically proven local recurrence remains controversial [4,8,12]. The tumor can be located in the prostatic fossa, can be disseminated systemically and possibly it is a combination of both.…”

“…The estimation of the risk of a local recurrence in these patients remains difficult. Four major retrospective studies have shown, that between 34% and 54% of patients with rising PSA after radical prostatectomy without clinical evidence of tumor have vital tumor found by punch biopsies of the urethro-vesical anastomosis [8,9,17]. However, the rate of distant metastasis at diagnosis of local recurrence is unknown.…”

“…Radiotherapy with 60-70 Gy has been shown to achieve undetectable PSA levels again in 30-70% of these patients [3,4,7,10,12,18]. Patients without primary infiltration of the seminal vesicles (pT3b), PSA < 2 ng/ml before radiotherapy and a PSA velocity of more than 6-12 months have a significantly higher success rate [8]. Furthermore, between 25% and 45% of all patients are biochemically tumor-free at 3-5 years and seem to have a curative chance [12].…”

“…In contrast, between 40% and 60% of patients with PSA increase after radical prostatectomy do not stand to profit from radiotherapy, as they consequently have later on a further increase of PSA, thus leading to metastases [3,8,12]. This fact illustrates the problem of identifying patients at high risk of tumor progression.…”