Whole pelvic salvage radiation + short-term ADT improves oncologic outcomes


We didn’t expect to see data from the SPPORT trial for another 2 years, but the research team hit their recruitment goal early and have already been able to provide 5-year results.Alan Pollack, the lead investigator, presented the early findings of this trial, also known as the NRG Oncology/RTOG 0534 trial, at the ongoing annual meeting of the American Society of Radiation Oncology (ASTRO), and commentary can also be found on the Medpage Today web site. The data proved that salvage whole pelvic radiation (sWPRT) together with short-term ADT (STADT) is superior to either prostate-bed only salvage radiation (PBRT) or prostate-bed only salvage radiation with short-term ADT (PBRT + STADT).

Between 2008 and 2015, at 460 locations in the US, Canada, and Israel, the research team randomly assigned 1,792 men with a biochemical or a clinical recurrence after prostatectomy to one of three therapies:

  1. sWPRT + STADT
  2. PBRT + STADT
  3. PBRT

Specifically,

  • ADT consisted of 4 to 6 months of a combination of an antiandrogen and an LHRH agonist starting 2 months before salvage radiation.
  • Radiation dose to the prostate was 64.8 to 70.2 Gy at 1.8 Gy per fraction.
  • Radiation dose to the pelvic lymph nodes was 45 Gy at 1.8 Gy per fraction.
  • The treated pelvic lymph node area was per RTOG guidelines and did not include the lymph nodes (that have often been found to be cancerous using modern PET scans).

Biochemical progression was assessed by using the so-called Phoenix criterion (nadir PSA level +2 ng/ml) because it correlated best with clinical progression.

The oncological results were as follows:

  • 5-year freedom from progression (biochemical or clinical) was
    • 89 percent for sWPRT + STADT
    • 83 percent for PBRT + STADT
    • 72 percent for PBRT
    • All three values were significantly different
  • 8-year incidence of metastases was
    • 25 percent for sWPRT + STADT (hazard ratio [HR] =  0.52)
    • 38 percent for PBRT + STADT (HR = 0.64)
    • 45 percent for PBRT
    • The sWPRT + STADT result was significantly better than the other two.

The reported toxicity results were:

  • GI grade 2 or higher: 7 percent for sWPRT + STADT vs. 2 percent for PBRT
  • Bone marrow grade 2 or higher: 5% percent for sWPRT + STADT vs. 2 percent for PBRT
  • Bone marrow grade 3: 2.6 percent for sWPRT + STADT vs. 0.5 percent for PBRT
  • Late-term bone marrow grade 2 or higher: 4 percent for sWPRT + STADT

There were some caveats:

  • The researchers found that the benefit of sWPRT + STADT was not maintained in men with very low PSA.
  • Further analyses are expected based on patient risk characteristics and genomic biomarkers.

We previously saw, in a retrospective study, that prostatectomy Gleason score had a significant influence. With better PET scans now, we can have more assurance that whole pelvic radiation is necessary. But at very low PSA (<0.2), even our best PET scans may not find the cancer. Also, it may be that long-term ADT may improve results even further, and that dose escalation may improve results. While this changes the standard of care for many men with persistent PSA and recurrences after prostatectomy, the patient and his radiation oncologist still must rely on judgment.

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

12 Responses

  1. Allen:

    It seems as though there may be some questions around whether the increased risk for adverse effects associated with sWPRT + STADT do or don’t outweigh the therapeutic benefit of this form of treatment compared to PBRT + STADT — most particularly in patients with a very low PSA level at time of treatment.

    Thoughts?

    Mike

  2. I agree. … When you edited, you listed only two of the points as caveats, but the entire last paragraph should be included as well. They found no effect to sWPRT + STADT in men with low PSA. The retrospective study I referred to suggested that men with low Gleason scores may benefit almost as much without ADT. I think a patient might also avoid it if there is a known positive margin to which one can reasonably attribute the residual PSA.

    Cleveland Clinic has an excellent nomogram showing whether prostate bed-only salvage is likely to be successful, given some important risk factors.

    On the other side of the equation, for some men, increasing the pelvic field size, increasing the radiation dose, and increasing the duration of ADT may be needed. There’s lots of room for judgment here.

  3. Allen – TYPE OF RADIATION TECHNIQUE USED FOR PELVIC NODES?

    I’ve read some of the background papers and the ClinicalTrials.gov information, but it is not absolutely clear that the pelvic radiation (25 sessions) was delivered to the entire pelvis, as I strongly expect it was, rather than to individual nodes, which seems impractical and not in line with “25 sessions” but is used for oligometastatic disease, which these patients did not have. The authors could have avoided this confusion by stating that the entire pelvic area was radiated rather than describing the radiation as pelvic node radiation.

    Do you have any insight about the curious wording?

  4. Type of ADT used in the third arm (pelvic radiation) of the SPPORT trial

    It is interesting and encouraging, to me at least, that the type of ADT used was combined ADT: an LHRH agonist plus an antiandrogen (bicalutamide or flutamide). I am one of those who find the evidence convincing that combined ADT (ADT2) is better than single agent ADT. I suspect the results for Arm 3 would not have been quite as good if just single-agent ADT had been used.

    It is understandable that the trialists did not allow triple ADT (ADT3 with the addition of a 5-ARI drug: either finasteride or dutasteride) as use of ADT3 is uncommon and not well supported by research. Personally, I believe the results would have been even a bit better if they had standardized to ADT3. (My own primary radiation in 2013 included a dose of 46 Gy to the entire pelvis and was supported by 18 months of ADT3, my fourth and hopefully final round of intermittent ADT3.)

  5. Dear Allen:

    I think I may be really splitting hairs here, but …

    The two items listed as “caveats” are based on the data currently available from the SPPORT trial itself. The content of the following paragraph is not , strictly speaking, a “caveat” that has anything to do with the SPPORT trial. It is a separate set of comments about current knowledge that need to be taken account of in assessing the value of the data reported from the SPPORT trial to date.

    As you carefully and rightly observe: “lots of room for judgment here”, and I was only trying to emphasize that point.

  6. Jim:

    They irradiated the entire pelvic lymph node area (using RTOG guidelines) with a dose of 45 Gy, and the prostate bed only with a dose of between 64.8 and 70.2 Gy. I don’t find that at all confusing.

  7. Thanks Allen. I still can’t find that clarifying statement, but you know the study far better than I do, and it certainly makes sense.

    Having thought it over, I’m thinking that: (1) the study officially kicked off in February 2008, with likely at least a year of preparation prior to that, and (2) the concept of treating oligometastatic prostate cancer was just in its infancy at that point. That would make the language of “treating the pelvic lymph nodes” at that earlier time a way of expressing treating the entire pelvic area, and the team would be used to that language.

  8. Dear Allen,

    Did the researchers give any details about “not maintained” in “the benefit of sWPRT + STADT was not maintained in men with very low PSA”?

    My PSA was 0.2 ng/ml 5 weeks ago and has increased from 0.13 ng/ml 2 months ago.

  9. They defined “low PSA” as ≥ 0.1 to ≤ 1.0 ng/mL at study entry. They wrote, “The research team also described preliminary data that for those with a very low PSA on study entry, there was no improvement from sWPRT+STADT over PBRT+STADT; although, this was an unplanned analysis.” So you may not need your pelvic lymph nodes treated. It’s a good option to discuss with your radiation oncologist.

  10. The third bullet under “8-year incidence of metastases was” doesn’t look correct to me. Shouldn’t it read only “45 for PBRT”? “(sWPRT + STADT” should be deleted, right?

  11. Thanks, Bruce. The original read “8-year incidence of metastases was 25 for sWPRT + STADT (HR = 0.52), 38 for PBRT + STADT (HR = 0.64), and 45 for PBRT (sWPRT + STADT was significantly better than the other two)”

    Mike must’ve inadvertently clipped it when he added the bullet points for easier reading.

  12. Bruce and Allen:

    Indeed. … My error. Duly corrected above.

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