Prostate adenocarcinoma salvage EBRT post radical prostatectomy

Target verification notes

• Consideration should be given to dose delivered from verification imaging and whether this needs to be accounted for in treatment planning, particularly with respect to critical OARs.

Efficacy

The evidence supporting this trial comes from observational studies^rr in addition to sub group analysis.

In a study of 2,657 men^r with biochemical failure post RP, 856 (32%) received Salvage RT. Median follow up following Salvage RT was 5.9 years and showed that the SRT significantly reduced the risk of local recurrence (HR 0.12; 95% CI 0.06 - 0.26; p<0.0001), systematic progression (HR 0.30; 95% CI 0.16 - 0.56; p=0.0002) and delayed the need for ADT. Salvage RT did not increase overall survival in this group of patients.

Trock et al^r retrospectively analysed 635 men who experienced biochemical and/or local recurrence where patients either received Salvage RT alone (n=160), SRT + ADT (n=78) or no treatment (n=397). After a median follow up of 9 years post RP and 6 years following recurrence, salvage RT alone and salvage RT + ADT was associated with a significant increase in prostate cancer specific survival relative to those who received no salvage treatment HR 0.32; (95% CI 0.19 - 0.54; P<0.001) and HR 0.34 (95% CI 0.17 - 0.69; P<0.003) respectively. The increase in survival was limited to men with PSA doubling time of less than 6 months and RT initiated more than 2 years after recurrence provided no significant increase in prostate cancer specific survival.

Currently the RAVES trial (TROG 08.03),^r a phase III multicentre randomised trial is underway (accrual closed late 2015) comparing adjuvant radiotherapy (RT) with early salvage RT in patients with positive margins or extraprostatic disease following RP.

In the absence of RCTs, the efficacy of salvage radiotherapy is difficult to interpret given differences in patient characteristics, treatment methods, duration of follow-up and definition of treatment failure in the retrospective series. The series conducted by Tendulkar et al^r provides the following information:

• 5-year Freedom from biochemical failure (FFBF) was 56% overall; 71% for those with a pre-SRT PSA level of 0.01 to 0.2 ng/mL (n = 441), 63% for those with a PSA of 0.21 to 0.50 ng/mL (n = 822), 54% for those with a PSA of 0.51 to 1.0 ng/mL (n = 533), 43% for those with a PSA of 1.01 to 2.0 ng/mL (n = 341), and 37% for those with a PSA > 2.0 ng/mL (n = 323); p<0.001.
• Statistically significant variables (p<0.05) associated with FFBF include: Pre-RT PSA level, Gleason score, extraprostatic extension, seminal vesicle invasion, surgical margins, ADT use and RT dose.
• Statistically significant variables (p<0.05) associated with increased risk of distant metastases include: Higher pre-RT PSA, higher Gleason Score, seminal vesicle invasion, negative surgical margins and lack of ADT.
• There is no subgroup of patients with a rising PSA post-prostatectomy who will definitely not benefit from salvage radiotherapy.
• Published nomograms^r may aid discussions with patients.

Use of ADT

The GETUG-AFU 16 Trial^r where patients who had a rising PSA of < 0.2 ng/L following RP but without clinical evidence of disease were randomised to receive Salvage RT (n=374) or RT + short term androgen suppression (goserelin, n=369). Median PSA at baseline randomisation for both groups was 0.30μg/L (range 0.20 - 0.50). Patients who received RT + ADT were significantly more likely to be free of biochemical progression or clinical progression (80% vs 62%; hazard ratio [HR] 0.50, 95% CI 0.38 – 0.66; p<0.0001).

Toxicity

A summary of the most clinically significant toxicities associated with this protocol are included in the table below:

(AAT = Anti-androgen Therapy)