The addition of pelvic lymph node treatment to salvage radiotherapy of the prostate bed

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We read the results of the SPPORT trial with great interest.
1
  • Pollack A.
  • Karrison TG
  • Balogh SA
  • et al.
The addition of androgen deprivation therapy and pelvic lymph node therapy to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicenter, randomized phase 3 trial .

Patients were randomly assigned to salvage prostate bed radiation therapy (PBRT), PBRT plus short-term androgen deprivation therapy (ADT), or PBRT plus short-term ADT plus prostate radiation therapy. pelvic lymph nodes (PLNRT). With a median follow-up of 8.2 years, the study showed a benefit in terms of no progression rate over 5 years of adding ADT and short-term PLNRT to PBRT.

According to the guidelines of the American Urological Association (AUA), biochemical recurrence of prostate cancer after surgery is defined as a detectable serum concentration of prostate-specific antigen (PSA) of 0.2 ng/mL or more, which is then confirmed by a second measurement of 0.2 ng/mL or more.
2
  • MS Cookson
  • Australia G
  • Burnet AL
  • et al.
Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the report of the American Urological Association Prostate Guidelines Update Committee for Localized Prostate Cancer and Recommendations for a standard in reporting surgical results.

According to the inclusion criteria,

1
  • Pollack A.
  • Karrison TG
  • Balogh SA
  • et al.
The addition of androgen deprivation therapy and pelvic lymph node therapy to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicenter, randomized phase 3 trial .

patients with PSA concentrations of 0·1–2·0 ng/mL were included. However, the endpoint of no progression was determined by the Phoenix definition, which is used worldwide for follow-up after definitive radiation therapy. We are interested in knowing the rationale for using the Phoenix definition, as most countries use the AUA definition of biochemical recurrence in the postoperative setting.

Two previous prospective studies have shown a benefit in disease-free survival when ADT is added to PBRT.
3
  • Carrie C.
  • Magne N.
  • Burban-Provost P
  • et al.
Short-term androgen deprivation therapy plus radiotherapy as salvage therapy after radical prostatectomy for prostate cancer (GETUG-AFU 16): 112-month follow-up of a randomized phase 3 trial.

,

4
  • Shipley WU
  • Seiferheld W
  • Lukka HR
  • et al.
Radiotherapy with or without antiandrogen in recurrent prostate cancer.

In SPPORT, the addition of short-term ADT to PBRT also improved the absence of progression results, as expected; however, the underlying rationale for benefiting from PLNRT is unclear. The role of PLNRT as salvage therapy is still controversial for node-negative patients. At least ten lymph nodes should be removed to establish accurate staging by lymph node dissection.

5
Current status of pelvic lymph node dissection in prostate cancer: the New York PLND nomogram.

However, only a median of six lymph nodes were removed,

1
  • Pollack A.
  • Karrison TG
  • Balogh SA
  • et al.
The addition of androgen deprivation therapy and pelvic lymph node therapy to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicenter, randomized phase 3 trial .

which is probably insufficient. PLNRT might have benefited patients with undissected occult lymphatic metastases. Based on these results, the application of PLNRT – which is more toxic than PBRT – might not be appropriate in patients without lymph node involvement. Could the positive effect be related to PLNRT possibly compensating for inadequate lymph node dissection?

Additionally, for patients with intermediate-risk prostate cancer who receive definitive radiotherapy, ADT is suggested for those classified in the unfavorable group but not for those classified in the favorable group. From this point of view, we believe that a personalized therapeutic approach taking into account the Gleason score and the PSA concentration at recurrence is important in the decision to apply ADT and PLNRT. In the treatment of prostate cancer, it would make sense to include breakthrough metabolic imaging methods in patient risk stratification.

In conclusion, while the SPPORT results are valuable and thought-provoking, clarification of the above issues would be helpful to better understand the implications of the results.

We declare no competing interests.

References

  1. 1.
    • Pollack A.
    • Karrison TG
    • Balogh SA
    • et al.

    The addition of androgen deprivation therapy and pelvic lymph node therapy to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicenter, randomized phase 3 trial .

    Lancet. 2022; 399: 1886-1901

  2. 2.
    • MS Cookson
    • Australia G
    • Burnet AL
    • et al.

    Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the report of the American Urological Association Prostate Guidelines update group for localized prostate cancer and recommendations for a standard in the reporting of surgical results.

    J Urol. 2007; 177: 540-545

  3. 3.
    • Carrie C.
    • Magne N.
    • Burban-Provost P
    • et al.

    Short-term androgen deprivation therapy plus radiotherapy as salvage therapy after radical prostatectomy for prostate cancer (GETUG-AFU 16): 112-month follow-up of a randomized phase 3 trial.

    Lancet Oncol. 2019; 20: 1740-1749

  4. 4.
    • Shipley WU
    • Seiferheld W
    • Lukka HR
    • et al.

    Radiotherapy with or without antiandrogen in recurrent prostate cancer.

    N Engl J Med. 2017; 376: 417-428

  5. 5.

    Current status of pelvic lymph node dissection in prostate cancer: the New York PLND nomogram.

    Can J Urol. 2011; 18: 5585-5591

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