Ciekawy artykuł z "Nature" z tezą, że raczej korzystniejsze dla pacjenta jest powstrzymanie się od radioterapii adjuwantowej (z ryzykiem wszelkich możliwych zdarzeń niepożądanych) na rzecz późniejszej radioterapii ratującej.
Salvage radiotherapy: a new standard of care
Adjuvant radiotherapy following radical prostatectomy (RP) has been shown to reduce the risk of disease recurrence in men with high-risk prostate cancer. Nonetheless, this strategy represents overtreatment for some, who would not otherwise have disease recurrence after RP.
Paul Sargos, a lead investigator on the GETUG–AFU 17 study explains: “Three randomized trials from the 1990s compared the efficacy of adjuvant radiotherapy, to that of observation after RP. These studies, which included patients with pathological high-risk features, indicated better long-term biochemical and/or clinical tumour control, albeit with higher rates of genitourinary, sexual and gastrointestinal toxicities,” adding that: “Interestingly, despite the positivity of these data, and, despite only retrospective evidence favouring an observation policy, observation followed by salvage radiotherapy at biochemical failure has been widely adopted in daily practice, predominantly by urologists and by some radiation oncologists.”
Now, data from three randomized controlled trials indicate no evidence of an improvement in 5-year event-free survival (EFS) with the adjuvant approach over early salvage radiotherapy.
Investigators in Australia and New Zealand (TROG 08.03/ANZUP RAVES), France (GETUG–AFU 17) and Canada, Denmark, Ireland, and the UK (RADICALS-RT) randomly assigned men with Gleason grade ≥6 prostate cancer with at least one risk factor for disease progression undergoing RP (1:1) to receive either adjuvant radiotherapy or salvage radiotherapy upon detection of a rising serum PSA level (either ≥0.2 ng/ml or >0.1 ng/ml and rising on three consecutive occasions). Each trial had a different primary end point: biochemical progression-free survival (bPFS), EFS and freedom from distant metastases, respectively.
In TROG 08.03/ANZUP RAVES, involving 333 patients, both groups had similar 5-year rates of bPFS (86% in the adjuvant radiotherapy group versus 87% in the early salvage group (stratified HR 1.12; Pnon-inferiority = 0.15)). This observation was accompanied by a significant increase in grade ≥2 genitourinary toxicities in those receiving adjuvant radiotherapy (70% versus 54%, OR 0.34; P = 0.0022).
Similarly, GETUG–AFU 17, involving 424 patients, revealed no significant difference in 5-year EFS (92% in the adjuvant radiotherapy group versus 90% in the early salvage group, HR 0.81, log-rank P = 0.42) also with fewer acute grade ≥2 toxicities (59% versus 22%) and late grade ≥2 adverse events (27% versus 7%; P < 0.0001). Unlike in TROG 08.03/ANZUP RAVES, patients in this trial also received a short course of hormone therapy.
These data were further confirmed in RADICALS-RT, involving 1,396 patients, which revealed similar rates of 5-year bPFS (85% in the adjuvant group versus 88% in the salvage group, HR 1.10; P = 0.56). Significant reductions in all radiation-related toxicities (diarrhoea, proctitis, cystitis, haematuria and urethral stricture, all P ≤ 0.02) were observed in the salvage group, although patient-reported outcome measures revealed only short-term (<1 year of randomization) reductions in self-reported urinary or bowel function.
These data provide robust evidence that men undergoing RP can safely be spared adjuvant radiotherapy and the associated risk of adverse events.
These conclusions are elegantly summarized in ARTISTIC, a prospectively planned, collaborative meta-analysis, which confirms a 1% difference in 5-year EFS between groups (89% with adjuvant, versus 88% with early salvage radiotherapy).
Sargos summarizes: “These three studies, added to the ARTISTIC meta-analysis results, are an important step forward and support the use of early salvage as opposed to adjuvant radiotherapy after RP for many patients. This is a practice changing conclusion!”
When asked about future directions, Chris Parker, a lead investigator on RADICALS-RT highlights: “Although the trial started 13 years ago, the results in terms of freedom from metastases and overall survival remain immature, with insufficient events currently accrued for analysis. We plan to continue follow-up monitoring in order to analyse these end points in due course.”
This article is modified from the original in Nat. Rev. Clin. Oncol.
(https://doi.org/10.1038/s41571-020-00443-3).
https://www.nature.com/articles/s41585-020-00392-7