Whole pelvic salvage radiation may be better than precisely targeted lymph node salvage radiation

Last week, I looked at a retrospective study of metastasis-directed therapy (MDT) at the Mayo Clinic among oligorecurrent patients (see this link). Oligorecurrent means that they had already received primary therapy (mostly prostatectomy) and some had received salvage radiation as well, but there were only 1 to 5 metastases detected. They found there was no benefit if there were any bone metastases, but there may have been a benefit if the metastases were in the lymph nodes only. Lymph nodes were treated with either surgery (called pelvic lymph node dissection — PLND) or radiation to a small area around the detected (by C-11 choline PET/CT) cancerous lymph nodes. I ended the analysis with this statement:

Another open question is whether whole pelvic salvage radiation might have been more effective than the limited margins they used at Mayo. With the more accurate PSMA PET scans, ROs are able to treat the entire PLN area with radiation boosts given to the detected ones. The RTOG-consensus treatment area has recently been expanded (see this link). It’s important that patients understand the detection limits of even the best PSMA PET scan: metastases smaller than 4 mm, and those that put out only small amounts of PSA remain invisible.

De Bleser et al. reported the results of a retrospective study to examine precisely this question among 506 oligorecurrent patients conducted at 15 different institutions throughout Europe. Patients were selected and treated as follows:

  • Detection of cancerous lymph nodes (LNs) was primarily (85%) with C-11 Choline PET/CT (a few with PSMA, FDG, or conventional imaging).
  • 309 patients were treated with SBRT (at least 5 Gy per fraction, up to 10 fractions). A margin of 2-6 mm was treated also.
  • 197 patients were treated with “Elective Nodal Radiation Therapy” (ENRT) of at least 45 Gy in 25 fractions to the entire pelvic lymph node area. Boost doses to detected LNs were allowed. A margin of 5-7 mm was treated. 60 patients also had their prostate bed simultaneously treated.
  • About half had already had salvage radiation to the prostate bed.
  • About half had already had PLND at the time of prostatectomy. The SBRT group had an average (median) of 1 positive LN at pathology, the ENRT group had 2.
  • Patients with adjuvant ADT for more than a year were excluded. Seventy-seven percent of the SBRT had no ADT; 40 percent of the ENRT group had no ADT. Those who had ADT, had it for an average (median) of 6 months.
  • Seventy-two percent had pelvic LNs only; 28 percent had extrapelvic LNs (retroperitoneal) at imaging.
  • Seventy-two of the SBRT group had only one LN at imaging; 50 percent of the ENRT group had 2 to 5 LNs at imaging.
  • Patients with bone or visceral metastases at relapse were excluded, as were patients already using ADT, and those with detected metastases before primary therapy.

After a median follow-up of 3 years:

  •  3-year Metastasis-free survival (MFS) was 68 percent at 3 years, but only distant metastases (M1) were counted.
  • >Among patients who were detected with only one positive LN at baseline, MFS was twice as long with ENRT compared to SBRT
  • There was no difference among patients with more than one positive node at baseline.
  • Fifty-seven percent of patients were detected with metastases (N1 and M1) in the SBRT group — 55 percent in pelvic LNs, 19 percent in extrapelvic LNs only, 20 percent in bone, and 6 percent in visceral organs.
  • Thirty-eight percent of patients were detected with metastases (N1 and M1) in the ENRT group — 11 percent in pelvic LNs, 43 percent in extrapelvic LNs only, 35 percent in bone, and 8 percent in visceral organs.
  • ENRT provided longer-lasting N1 control, but did not delay M1 control any more than SBRT.
  • Castration-free survival did not differ between the two types of treatments.
  • There was no acute toxicity reported for 99 percent of men receiving SBRT and 94 percent of men receiving ENRT. Grade 3 (serious) toxicity was reported for five men receiving ENRT and none receiving SBRT.
  • Similarly, there was no serious late-term toxicity reported for SBRT, and 2.5 percent for ENRT.

We conclude that ENRT provided better local (pelvic lymph node) control than SBRT, but neither seemed to delay distant metastases better. MFS was only improved by ENRT if there was just one LN metastasis detected at baseline. Reported toxicity (acute and late-term) was low, but was lower with SBRT.

Of course, this retrospective study leaves many questions unanswered:

  • Does either treatment improve MFS over ADT alone
  • What would have happened if long-term ADT were allowed rather than just 6 months (see this link)?
  • What if all patients received the same radiation dose, the same treatment margins, and a standard treatment area (up through the aortic bifurcation) were used?
  • What would have happened if LN metastases were detected with PSMA PET/CTs rather than C-11 choline PET/CT?
  • What were the patient-reported quality of life outcomes?

These questions will be addressed in two ongoing randomized clinical trials:

  • OLIGOPELVIS2 (in France) is randomizing oligorecurrent patients to intermittent ADT with or without whole-pelvic IG/IMRT with a boost to PSMA-identified LNs (completion expected mid-2026).
  • PEACE V (a.k.a STORM; in Europe and Australia) is randomizing oligorecurrent patients to MDT by either SBRT/salvage PLND or ENRT. C-11 choline, PSMA or Axumin PET scans will be used for detection (completion expected end of 2023).

Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink.

4 Responses

  1. Very well written and a good discussion but in my patient experiences with RP, salvage RT to bed and salvage EPLND crucial patient perspectives and leading edge science are not covered. Once prostate cancer is out we face ADT before death unless something else gets us first. I strive to do all I can to not be one of the 30K+ American men who die each year of this disease nor one of the near 500K that are on life extending/altering ADT. After my salvage RT failed, 3 years ago, all American doctors offered me was chemotherapy and ADT.

    Still seeking a curative attempt I went to the Netherlands at usPSA 0.1, yes 0.1, for a PSMA PET/CT scan combined with nanoparticle MRI (Ferrotran). Cancerous nodes smaller than the limits cited in the article were identified. This lead to salvage extended PLND in Belgium — could not find a doctor in the US willing to do this. Outcome was usPSA <0.006.

    Am I “cured”? Based on data, this seems unlikely — I accepted this before surgery in Belgium. My objective was to push back my need for life-extending ADT and chemotherapy. Well all available science indicates this goal has been achieved — 3 years out and testing every month.

  2. What about the quality of life for these men? Beyond “acute toxicity”, did the researchers collect data on this?

  3. Murray:

    I strongly recommend you consider continuing with systemic therapy. The Combidex MRI you had can find lymph node tumors down to 2 mm, which represents clumps of several million cancer cells. That leaves millions of metastatic cancer cells that you can’t see. ADT can reduce those hidden cells. You have treated PSA; now, I hope you will treat the cancer in your body (
    see this link

  4. Vince:

    This was a retrospective study. There is usually only QOL data collected on prospective clinical trials.

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