New guidelines for salvage radiation dimensions


It has always been troubling that only about half of all salvage radiation treatments after failure of radical prostatectomy are successful. Usually, only the prostate bed is treated. But sometimes recurrent patients (or those with persistently elevated PSA) receive salvage radiation to the pelvic lymph nodes as well, or subsequently. Radiation oncologists here in the USA usually follow RTOG (now called NRG Oncology) guidelines on what constitutes the dimensions of the prostate bed and the pelvic lymph nodes.

Prostate Bed Coverage

Often, the cancer has only penetrated into the bed or fossa. This is especially suspected if there are significant positive surgical margins. The 2010 RTOG consensus guidelines were updated in 2020 by the Francophone Group of Urological Radiotherapy (GFRU) based on standard imaging (MRI and CT). Harmon et al. reported on 45 patients within the LOCATE trial who received a positive Axumin PET/CT upon recurrence or persistent PSA after prostatectomy.

  • 30 patients had cancer in the prostate fossa
  • The 2010 RTOG guidelines completely or partially missed cancer in 33% of the patients
  • The 2020 GFRU guidelines completely or partially missed cancer in 10% of the patients

The new GFRU guidelines are clearly superior in terms of oncological outcomes, but toxicity must be considered as well.

Pelvic Lymph Node Coverage

In 2020, NRG Oncology revised its previous 2009 RTOG pelvic lymph node coverage consensus guidelines based on MRI and PET scans. They recommended coverage as high as the aortic bifurcation or common iliac lymph nodes (whichever is higher, depending on patient anatomy), which is about the level of the L4 and L5 vertebrae. The expanded coverage area extends down to the pre-sacral nodes at the bottom of vertebra S3. Harmon et al. also validated the expanded NRG Oncology guidelines based on Axumin PET/CT scans. They found:

  • There were 43 sites of cancer in the pelvic lymph nodes.
  • The 2009 RTOG guidelines completely or partially missed 32 percent of the nodal cancers.
  • The 2020 NRG Oncology guidelines completely or partially missed none of the nodal cancers

The SPPORT trial found that treating pelvic lymph nodes prophylactically improved outcomes, but wasn’t necessary in patients with low PSA. This study did not examine the toxicity of the expanded coverage. The wider margins of the prostate bed will probably increase genitourinary toxicity. Careful contouring of the pelvic lymph node area to exclude bowel, bone, bladder, and muscle seems to prevent excess toxicity at the doses usually used (45.0 to 50.4 Gy). In one recent study of high-risk patients, a pelvic lymph node dose as high as 56 Gy was used without extra toxicity. Boosted site doses can also be utilized where PET/CT or MRI has identified specific tumors. However, treatment should not be delayed until such tumors become apparent on imaging.

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

14 Responses

  1. As salvage RT to bed missed some of my remaining cancer following RP, “Troubling” is not how I would characterize the success rate, or failure rate of salvage RT.

    Once out, finding all the cells is just not yet possible. Instead of salvage RT to pelvic region, I traveled from Texas to Netherlands for nanoparticle MRI combined with PSMA PET/CT at usPSA 0.1. This lit up five suspicious nodes. I then went to Belgium for salvage extended pelvic lymph node dissection. Outcome usPSA < 0.006. What troubles me is that the US remains so far behind .

  2. So grateful you wrote this up, Mr. E … it comes up about once a month in the context of early or late salvage RT. Now we have your article to cite!

    Thank you!

  3. I disagree with @Murray that the US remains far behind.

    For 15 years or more leading academics have recommended pelvic girdle radiation together with hormone therapy to treat recurrent disease. While controversial, it has been available and studied.

    Anecdotally, we have never seen lymphadenectomy offer the same success. Allen can tell us if they have ever been compared head to head.

    It is not necessary to travel overseas for complete treatment — just advocate for yourself here and find one of the many radiation oncologists who will radiate the entire pelvic girdle AND combine it with sufficient hormone therapy!

  4. Murray:

    Even the Combidex MRI won’t find all cancerous LNs, and removing just the ones that can be found using ePLND (or SBRT) will almost certainly miss some of the cancer in the pelvic LNs. The recent Mayo study demonstrated the defects in such a strategy:

    Rick:

    Happy to be useful to you!

  5. Rick:

    As a patient that benefited from Combidex MRI (now Ferrotran) in January 2018 at usPS 0.1 and subsequent ePLND I am stunned by “Even the Combidex MRI …” and “the defects in such a strategy:” Prior to my Combidex imaging Mayo, MDA and several others offered me standard NCCN treatment guidelines. Instead I went for Combidex in Netherlands and salvage ePLND in Belgium. My post-surgery usPSA nadir was < 0.01 and even < 0.006. As my para-aortic nodes were found to have cancer I do not consider myself cured. In fact for past year I have been on monthly PSA testing as my PSA has risen to 0.026 ng/ml; noting still well below the AUA recurrence guideline of 0.2 ng/ml. IMO the study you cite is inadequate and misleading. Happy to be a patient willing to share my independent experiences outside of established US healthcare guidelines.

    Murray

  6. Good discussion Rick. I did my ePLND after salvage RT to prostate bed — PSA nadir < 0.01 and < 0.06 — no ADT. The imaging methods and experiences evaluating the imaging results I went to England and Netherlands for still cannot be found in the US — this is a fact. The salvage extended pelvic lymph node surgery I went to Belgium for is not easily found (available) in US; I was turned away for this procedure by top centers — this is a fact. I went to London in 2015 for consultations on CyberKnife and HIFU — well ahead of US then and today. Imaging prior to any treatment decision is far more common in Europe than US – this is a fact.

    Murray

  7. Murray:

    You write “the study you cite is inadequate and misleading” but you don’t say in what way is it inadequate and misleading.

    The new guidelines may cover the para-aortics in some patients.

    As you’ve learned, ePLND isn’t practiced much in the US because there is no proven advantage over whole pelvic salvage radiation and the side effects are worse.

  8. Murray:

    I’ll let you argue the toss with Allen re what he wrote..

    Had you spoken with us at AnCan prior to your first salvage RT, we likely would have suggested you raise full pelvic girdle radiation with your RO when all you got was a narrow field radiating the prostate bed.

    We had that very conversation with two men today in our group. You can listen later in the week on our YouTube Channel.

  9. Rick:

    I discussed full pelvic girdle radiation with top centers across the country. I choose narrow field and remain glad I did. My point is the US needs to catch up with Europe on imaging so we are no longer radiating blind. If I could do it all over I would have had nanoparticle MRI combined with PSMA PET/CT before my primary treatment, which was RP — but I was not aware of this imaging in 2015 despite its availability in Europe.

    As a side note, your reference to my”‘first salvage RT” suggests I have had a second. I have not — just one. After salvage RT failed to get all my remaining cancer I had salvage extended lymph node surgery in Belgium because I could not find this available in US. Over 3 years hence and I remain “undetectable” per AUA and CDC guidelines — however I think these agencies have this wrong.

    Murray

  10. Allen,

    My side effects from ePLND are not “worse” and your statement that they are worse is irresponsible. In fact I am doing great over 3 years later, and I am in excellent health and very fit. Just yesterday I enjoyed another challenging hike in mountains, over 9 miles above 9,000 feet. As far as the study, not sure it is worth a further discussion as you and Rick seem to discount my patient experiences.

    Murray

  11. Murray,

    My comments are about the average patient, not about you personally. ePLND carries significant risk of lymphocele and lymphedema. You were lucky; others may not be.

  12. “Lucky”? Repeatedly you have been judgmental and critical of my efforts. Not once have you asked me — a self-directed patient, a single question. Stunning treatment bias, arrogance, and ignorance.

    Murray

  13. Can you kindly provide the peer reviewed studies that support your statements that ePLND side effects are worse? Interested to see the patient selection criteria and if MRI was utilized in treatment selection.

  14. Sure. Here are some reports about salvage ePLND and about salvage whole-pelvic radiation (sWPRT):

    “The extent of PLND was confirmed to be an independent predictor of lymphocele formation (RR: 1.77; p < 0.00001)"
    https://www.sciencedirect.com/science/article/abs/pii/S2588931121000353

    "Patients undergoing super-extended LND have a lower chance of regaining both urinary continence [hazard ratio (HR) 0.59, 95% CI 0.39-0.90, p = 0.026] and Erectile Function (HR 0.28, 95% CI 0.13-0.57, p = 0.009)."
    https://www.frontiersin.org/articles/10.3389/fonc.2017.00280/full

    " In the extended lymph node dissection group, 12 patients (60%) had complications, compared with 21 patients (28.8%) in the limited lymph node dissection group (p=.016)"
    https://www.sciencedirect.com/science/article/abs/pii/S0210480615001916

    "Lymph node dissection induced more wound, respiratory, cardiovascular and neuromusculoskeletal events. It also caused more readmissions than no lymph node dissection (14.6% vs 6.3%)."
    https://www.auajournals.org/doi/10.1016/j.juro.2014.08.091

    "the diagnosis [of symptomatic venous thromboembolic events] was significantly associated with nonO blood type (OR 1.98, p = 0.004), an increasing number of lymph nodes removed (OR 1.05, p = 0.035) and blood transfusion (OR 1.30, p = 0.02). Patients with venous thromboembolic events were significantly more likely to die within 30 days of surgery (3.0% vs 0%, p <0.001)."
    https://www.auajournals.org/doi/10.1016/j.juro.2013.10.062

    As opposed to the most recent trial of escalated dose salvage whole pelvic radiation: "No RTOG grade IV toxicity was observed. Acute GI and GU toxicities were similar between both the arms {whole pelvic vs prostate-only radiation therapy). Cumulative ≥ grade II late GI toxicity was similar for WPRT and PORT (6.5% vs. 3.8%, p = 0.39) but GU toxicity was higher (17.7% vs. 7.5%, p = 0.03)…There was no difference in QOL scores of any domain between both arms."
    https://www.thegreenjournal.com/article/S0167-8140(19)33506-6/fulltext

    "Acute and late toxicity [of extended salvage whole pelvic RT] was mild to moderate, no grade-3 adverse events were observed."
    https://www.sciencedirect.com/science/article/abs/pii/S1896112616000122

    "Rates of severe side effects (grade three or higher using CTCAEv3.0) were low across treatment groups. During treatment, the main additional severe effects from PLNRT were in relation to blood/bone marrow events. For long-term effects, blood/bone marrow events were also slightly higher in the PLNRT arm, but only for grade 2+ events (4.1 percent), not grade 3+ (1.1 percent)."
    https://www.astro.org/News-and-Publications/News-and-Media-Center/News-Releases/2018/Combined-therapy-including-pelvic-lymph-node-radia

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