Adjuvant radiotherapy not recommended after radical prostatectomy

In men with prostate cancer who underwent radical prostatectomy (RP), adjuvant radiotherapy (RT) showed no benefit in terms of PSA* biochemical progression and increases the risk of urinary morbidity compared with salvage RT, the RADICALS**-RT trial suggests.

“No advantage was seen in biochemical control after RT, or in delaying the need for subsequent hormone therapy … These initial results do not support routine administration of adjuvant RT after RP,” said the researchers. “[Our] findings strengthen the case for a policy of observation after RP, with early salvage RT reserved for use only in patients with PSA biochemical progression. Most individuals following such a policy will avoid the need for RT.”

Within 22 weeks after RP, 1,396 men (median age 65 years) were randomized 1:1 to receive adjuvant RT or close observation with salvage RT to the prostate bed with or without pelvis, given in the event of PSA biochemical progression***. [Lancet 2020;396:1413-1421]

At 5 years, the rates of biochemical progression-free survival were similar between the adjuvant and the salvage RT arms (85 percent vs 88 percent; hazard ratio [HR], 1.10; p=0.56), as were the rates of freedom from non-protocol hormone therapy (93 percent vs 92 percent; HR, 0.88; p=0.53).

The rates of grade 3/4 haematuria in both study arms were low in the first 2 years (3 percent [adjuvant RT] vs <1 percent [salvage RT]) and >2 years after randomization (4 percent vs <1 percent, respectively). However, self-reported urinary incontinence was worse at 1 year with adjuvant vs salvage RT (mean score, 4.8 vs 4.0; p=0.002), and more men in the adjuvant RT arm had grade 3/4 urethral stricture within 2 years (6 percent vs 4 percent; p=0.02).

Is late better than early?

Salvage RT avoids unnecessary treatment in men cured by surgery alone, thus sparing men from radiation and leading to less treatment-related morbidity, the researchers pointed out. The ESMO^# appears to support this theory, based on their guidelines stating, ‘immediate postoperative RT after RP is not routinely recommended’, they added.

Older studies, despite having favourable outcomes, may be difficult to interpret in the context of contemporary clinical practice, as salvage RT in these studies was not timely. [J Urol 2009;181:956-962; Lancet 2012;380:2018-2027; Eur Urol 2016;70:751-757] “These older trials are therefore of limited use in determining the optimum timing of postoperative RT,” said the researchers.

“[Overall,] the weight of current evidence does not suggest that adjuvant RT confers a worthwhile long-term benefit in comparison with a salvage RT policy … In the absence of any reliable evidence that adjuvant RT does more good than harm, observation with salvage treatment for PSA biochemical progression should be the current standard of care after RP,” they stressed.

Will additional treatment help?

Studies have shown the benefit of adding hormone therapy to salvage RT. [Int J Radiat Oncol Biol Phys 2005;61:1285-1290; Int J Radiat Oncol Biol Phys 2012;83:960-965; Lancet Oncol 2016;17:747-756] In RADICALS-RT, about 30 percent of men also received hormone therapy. “[While it] might have improved outcomes, there is no evidence that it would have had a differential effect,” noted the researchers.

Another study underscored the benefit of treating pelvic lymph nodes in addition to the prostate bed among men receiving salvage RT. [Lancet Oncol 2019;20:1740-1749] Although this was allowed in RADICALS-RT, almost all (>95 percent) participants received treatment to the prostate bed only. “Once again, there is no evidence that pelvic nodal RT would have a differential effect in the adjuvant or salvage setting,” they added.

“[These treatment] advances … provide another argument in favour of a salvage RT policy. Given that patients might receive salvage RT years after [RP], they could benefit from new knowledge not available in the immediate postoperative period,” they said.