Salvage radiation therapy after radical prostatectomy for prostate cancer

Defined as radiation treatment for suspected recurrent malignant disease after a period of observation after prostatectomy.

This is to be distinguished from adjuvant radiation treatment directly after prostatectomy in patients potentially without residual disese and with an undetectable PSA.

Randomized trials have shown adjuvant radiation therapy provides benefit, whereas salvage radiation therapy evidence is lacking (Parker C).

For 635 patients who underwent radical prostatectomies for T1 and T2 disease with PSA relapse, only, were randomized to local salvage radiation alone or in combination with hormonal therapy-397 men did not receive salvage radiation , 160 received salvage radiation alone and 78 received salvage radiation plus hormonal therapy: salvage radiotherapy for biochemical relapse at a median follow-up of 6 years resulted in a threefold lesser risk for prostate associated deaths, hormonal therapy did not lead to significantly longer prostate cancer specific survival associated with salvage radiotherapy, survival benefit with salvage radiation benefit was limited to men with PSA doubling time of less than 6 months and if salvage radiotherapy was initiated more than 2 years after recurrence was not associated with survival prostate cancer specific survival, and finally if PSA did not become undetectable after salvage radiotherapy there was no benefit (Dreicer).

Adjuvant radiation therapy given for patients at high risk for recurrence: tumor outside the capsule, positive surgical margins or seminal vescal involvement.

Salvage radiation therapy for prostate cancer patients having a recurrence years after radical prostatectomy and the elevation in the PSA may reflect local recurrence, seminal vesicle involvement, pelvic or distant metastases.

It is estimated that pateitns with salvage radiation have roughly 10 times the tumor burden than patients with planned adjuvant radiotherapy (King CR).

Immediate adjuvant radiotherapy for high risk patients, pT3, proven to be beneficial: The European Organisation for Research and Treatment of Cancer (EORTC) 22911 showed a biochemical progression free survival, 74% vs. 52.6%, improved clinical progression free survival, and a significantly lowered rate of cumulative locoregional failure (Bolla M).

Adjuvant radiation for prostate cancer in a randomized trial ARO96-02AUO biochemical progression free survival significantly improved over observation group (72% vs. 54%), but treatment effect positive for patients with positive margins, Gleason score 6 or less, and pre-op PSA >10 ng/mL.

Radical prostatectomy may cure more than half of men considered to have high-risk tumors, but biochemical recurrence is possible in about 30% of patients with adverse features. 


Surgery is often followed by adjuvant radiotherapy to the prostate bed. 


Alternatively, patients may be observed after surgery, with radiotherapy only given once their prostate-specific antigen (PSA) levels start to rise. 


Salvage radiotherapy avoids unnecessary treatment of those cured by surgery alone.


Three phase III randomized trials and a meta-analysis of the three trials showed that adjuvant radiotherapy did not have any benefit compared with salvage radiotherapy in men with early, high-risk prostate cancer.


Observation, with salvage radiotherapy for biochemical progression, should be the current standard of care for most patients with prostate cancer.


Earlier studies  showing that adjuvant radiotherapy was associated with a decreased risk of recurrence in at-risk patients were confounded by either late use of salvage radiotherapy or no use of post-radical prostatectomy PSA monitoring or both.


Consensus regarding the optimal timing of radiotherapy after prostatectomy remains unmet.


A 2018 survey of 88 radiation oncologists found that 55% recommended adjuvant radiotherapy and 45% recommended salvage radiotherapy in the event of a recurrence.


RADICALS-RT trial included 1,396 patients with localized prostate cancer with a mean age 65, median PSA at diagnosis 7.9 ng/mL and associated with at least one high-risk characteristic pathologic T-stage 3 or 4, Gleason score 7-10, positive surgical margins, or preoperative PSA ≥10 ng/mL.


All patients underwent radical prostatectomy and were randomized to early adjuvant radiotherapy or to a watch-and-wait strategy of salvage irradiation. In the adjuvant group, radiation therapy was delivered within 6 months in 93% of patients, whereas a third of patients in the salvage group received radiotherapy within 8 years of surgery.


The 5-year biochemical progression-free survival (PFS) rate was 85% for patients in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group.


This would mean that most men might avoid 20 or more trips to the hospital for radiotherapy and the accompanying costs and side effects of additional treatments. Ideally, they could be monitored, with radiotherapy given only when the cancer recurs.


The RAVES  trial, and the GETUG-AFU 17 trial, as well as a meta-analysis all concluded similar results 


The trials had demonstrated noninferiority of salvage radiotherapy, defined as a 5-year biochemical PFS rate within 10% of the rate for adjuvant radiotherapy.


The results of one study showed a 5-year biochemical PFS rate of 86% with adjuvant radiotherapy versus 87% with salvage radiotherapy.


Patients allocated to adjuvant radiation therapy had a higher incidence of grade ≥2 genitourinary toxicity.


Data support the use of salvage radiotherapy, as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity.


The GETUG-AFU 17 randomized trial included 424 patients: After a median follow-up of 75 months, the adjuvant group had a 5-year EFS rate of 92% versus 90% for the patients allocated to delayed radiation therapy.


Meta-analysis of the three trials showed no evidence that event-free survival was improved with adjuvant radiotherapy compared with early salvage radiotherapy.


Three trials and a meta-analysis of trials failed to show a significant effect of adjuvant radiotherapy on biochemical progression or combined clinical events after radical prostatectomy for early, high-risk prostate cancer.


In the largest of the three trials, salvage radiotherapy was associated with a 3% absolute advantage for biochemical progression free,  at 5 years, not reaching statistical significance. 


The meta-analysis yielded a 5-year EFS rate of 89% with adjuvant radiotherapy and 88% with salvage therapy, also not significant.


The  studies support the use of early salvage as opposed to adjuvant radiotherapy for many patients after radical prostatectomy, with the possible exception of those at high risk for progression, which comprises less than 20% of men in the three randomized trials, and for whom shared patient and clinician decision making should be considered.



One reply on “Salvage radiation therapy after radical prostatectomy for prostate cancer”

If I understand this, salvage radiotherapy after a PSA recurrence following prostate removal is not more effective with the addition of hormone therapy. Is stereotactic radiation more effective or less damaging than regular radiation treatment?

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