APCCC 2022: Who Needs Early Salvage RT and Who Needs Adjuvant RT in 2022?

(UroToday.com) The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on biochemical recurrence, and a presentation by Dr. Kosj Yamoah discussing who needs early salvage radiotherapy and who needs adjuvant radiotherapy in 2022. Dr. Yamoah started by noting AUA/ASTRO key definitions are as follows:

  • Adjuvant radiotherapy: Administration of radiotherapy to post-prostatectomy patients who are at higher risk of recurrence because of adverse pathological features prior to evidence of disease recurrence
  • Salvage radiotherapy: Administration of radiotherapy to the prostatic bed and possibly surrounding tissues in a patient with PSA recurrence after surgery but no evidence of distant metastatic disease
  • Biochemical recurrence: post-surgery – detectable PSA > 0.2 ng/mL with a second confirmatory level > 0.2 ng/mL; post-radiotherapy (Phoenix) – PSA nadir + 2 ng/mL

 

The NCCN definitions are as follows:

  • Adjuvant radiotherapy – (i) typically given within 1-year post-prostatectomy after side effects have stabilized/improved, (ii) there no evidence of recurrence at the start of radiotherapy, (iii) treatment is initiated due to pathologic high-risk features
  • Salvage radiotherapy – post-prostatectomy PSA > 0.2 ng/mL followed by another higher value or a single PSA > 0.5 ng/mL

 

 Data from meta-analyses for adjuvant radiotherapy trials suggests that there is a benefit of adjuvant radiotherapy for biochemical recurrence (HR 0.48, 95% CI 0.42-0.55) and metastasis (HR 0.77, 95% CI 0.62-0.95), but no benefit for overall survival (HR 0.95, 95% CI 0.79-1.14) or GI/GU toxicity (HR 2.57, 95% CI 1.22-5.39). Dr. Yamoah suggests that yes, immediate post-prostatectomy radiotherapy improves outcomes for patients with high-risk features, particularly for patients with positive margins, extraprostatic extensions and seminal vesicle invasion compared to surveillance. However, when discussing whether early salvage radiotherapy is superior to adjuvant radiotherapy, it is important to highlight that adjuvant radiotherapy involves exposing some patients to radiotherapy side effects that would have never recurred, and salvage radiotherapy involves waiting for recurrence that could theoretically allow for progression to metastatic disease for select high risk patients.

Hwang et al.1 previously assessed adjuvant versus early-salvage post-prostatectomy radiotherapy for prostate cancer with adverse pathological features. In this multi-institutional, propensity score-matched study involving 1,566 patients, 1,195 had PSA levels of 0.1 to 0.5 ng/mL and received early salvage radiotherapy and 371 patients had PSA levels lower than 0.1 ng/mL and received adjuvant radiotherapy. Adjuvant radiotherapy, compared with early salvage radiotherapy, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]):

 

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 With regards to the timing of salvage radiotherapy, Dr. Yamoah discussed the RADICALS,2 GETUG-17,3 and RAVES4 trials in the context of the ARTISTIC meta-analysis. The ARTISTIC collaboration was a preplanned, prospective effort to undertake a meta-analysis of each of the three trials comparing adjuvant and early salvage radiotherapy.5 Across the three trials, a total of 1,074 men were randomized to adjuvant radiotherapy and 1,077 to an early salvage strategy. Despite some differences in patient population and study design, the findings of the three trials were remarkably similar: there was no significant improvement in biochemical event-free survival for patients receiving adjuvant radiotherapy (HR 1.12, 95% CI 0.88 to 1.42). Further, among patients randomized to an early salvage strategy, 395 (37%) have thus far commenced salvage radiotherapy and the remainder have been spared therapy.

 

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When deciding between adjuvant versus salvage radiotherapy, Decipher may identify patients who benefit from adjuvant radiotherapy. Den and colleagues6 examined 188 patients with pT3 prostate cancer or with positive surgical margins at the time of radical prostatectomy who received post-operative radiotherapy. In patients with a low genomic classifier score, there was no difference in rates of metastasis between patients who received adjuvant and salvage radiotherapy. However, in patients with higher genomic classifier scores, patients who received adjuvant radiotherapy had significantly lower rates of metastasis compared to those who were treated with salvage radiotherapy:

 

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Dr. Yamoah concluded his presentation by emphasizing that patients who need adjuvant radiotherapy are those with pathologic T3b/T4 disease, pathologic Gleason score >= 8, those with lymph node invasion, and men with a high Decipher score:

 

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Presented By: Kosj Yamoah, MD, PhD, Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

 

Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Annual Hybrid Meeting, Lugano, Switzerland, Thurs, Apr 28 – Sat, Apr 30, 2022.


References:
  1. Hwang WL, Tendulkar RD, Niemierko A, et al. Comparison between adjuvant and early-salvage postprostatectomy radiotherapy for prostate cancer with adverse pathological features. JAMA Oncol. 2018;4(5):e175230.
  2. Parker CC, Clarke NW, Cook AD, et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): A randomized, controlled phase 3 trial. Lancet 2020;396(10260):1413-1421.
  3. Sargos P, Chabaud S, Latorzeff I, et al. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localized prostate cancer after radical prostatectomy (GETUG-AFU 17): A randomized, phase 3 trial. Lancet Oncol 2020;21(10):1341-1352.
  4. Kneebone A, Fraser-Browne C, Duchesne GM, et al. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): A randomized, controlled, phase 3, non-inferiority trial. Lancet Oncol. 2020;21(10):1331-1340.
  5. Vale CL, Fisher D, Kneebone A, et al. Adjuvant or early salvage radiotherapy for the treatment of localized and locally advanced prostate cancer: A prospectively planned systematic review and meta-analysis of aggregate data. Lancet 2020 Oct 31;396(10260):1422-1431.
  6. Den RB, Yousefi K, Trabulsi EJ, et al. Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy. J Clin Oncol 2015; 33(8):944-51.

 

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