The decision about whether or not to treat the entire pelvic lymph node area along with the prostate (called whole pelvic radiation therapy or WPRT) or to treat just the prostate with a margin around it (called prostate-only radiation therapy or PORT) has long been a matter of judgment. Now we have proof of its benefit in most high-risk patients. Murthy et al. reported the results of “POP-RT,” a randomized clinical trial conducted among 224 high-risk and very high-risk patients treated at the Tata Memorial Hospital in Mumbai, India between 2011 to 2017. What sets this trial apart from previous trials that had equivocal results (like RTOG 9413 and GETUG-01) are the rigorous patient selection criteria and the now-proven treatments they received. Eighty percent of patients were screened using PSMA PET/CT to rule out those with already-detectable lymph node or distant metastases. The rest were staged using bone scan/CT. Local staging (T1-T4) was done with CT, MRI, and physical examination. Patients had to have a probability of microscopic lymph node metastases of greater than 20 percent using the Roach formula:
Probability of cancer in pelvic lymph nodes = (⅔ x PSA) + (10 x (Gleason score – 6))
This meant that high-risk patients had to have the following risk characteristics:- If Gleason score 8-10: any PSA, T1-T3aN0M0
- If Gleason score 7: PSA > 15 ng/ml, T1-T3aN0M0
- If Gleason score 6: PSA > 30 ng/ml, T1-T3aN0M0
- Also, any other “very high-risk”patients, including T3b-T4N0M0, with any Gleason score, any PSA, if their Roach probability was > 20 percent
- In this group of patients, the median Roach probability was about 40 percent and the median PSA was 28 ng/ml.
- Prostate dose= 68 Gy in 25 fractions or treatments (equivalent to about 81 Gy in 40 treatments)
- Pelvic lymph node dose = 50 Gy in 25 treatments (note: this is somewhat higher than the 45 Gy in 25 treatments that is usually given)
- Pelvic lymph nodes up to the aortic bifurcation were treated, which conforms to current RTOG specifications.
- ADT was started 2 months before IMRT and continued for a total of 2 years
- Note: this trial began before ASCENDE-RT proved the superiority of brachy boost therapy, but used a higher IMRT dose and longer ADT. This high-dose IMRT/long-term ADT treatment was proven effective by the DART 01/03 GICOR trial.
- 5-year biochemical failure-free survival was 95 percent for the WPRT group vs. 81 percent for the PORT group.
- 5-year disease-free survival, which means they had no PSA progression and no radiographic progression, was 90 percent for WPRT (15 recurrences) vs 77 percent for PORT (36 recurrences).
- 5-year metastasis-free survival, which is a good surrogate endpoint for overall survival, was 95 percent for WPRT vs 88 percent for PORT.
- Younger patients (< 66 years) derived more benefit from WPRT.
- Among those with recurrences, most (52 percent) of the recurrences in the PORT arm were in pelvic lymph nodes, whereas few (12.5 percent) were nodal recurrences in the WPRT arm.
- Acute grade 2 or greater gastrointestinal (GI) toxicity was 33 percent for WPRT vs 25 percent for PORT (not statistically different)
- Acute grade 2 or greater genitourinary (GU) toxicity was 33 percent for WPRT vs 24 percent for PORT (not statistically different)
- Late-term grade 2 or greater GI toxicity was 8.2 percent for WPRT vs 4.5 percent for PORT (not statistically different)
- Late-term grade 2 or greater GU toxicity was 20.0 percent for WPRT vs 8.9 percent for PORT (statistically different)
- Very few patients in either arm suffered serious (grade 3) toxicity, and there was no grade 4 toxicity.
- While higher rectal radiation doses were not associated with higher bowel toxicity, higher bladder doses were associated with higher urinary toxicity.
- Patient-reported outcomes were not significantly different for urinary, bowel, or sexual adverse effects.
Filed under: Diagnosis, Management, Risk, Treatment | Tagged: outcome, pelvic, prostate-only, radiation, risk |
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Re “this trial began before ASCENDE-RT proved the superiority of brachy boost therapy, but used a higher IMRT dose and longer ADT.”
Did POP-RT use same dosage and ADT duration as the ASCENDE-RT trial?
In this day and age there is little reason to agree to blind whole pelvic radation without first having PSMA PET imaging to investigate whether or not there are tumors and if so how many, where, and how large.
Dear Jon:
While your comment is theoretically accurate, the critical question would be whether — for relevant patients — the patients’ insurance covered the costs of PSMA PET imaging and whether it was easily accessible for them.
I’m somewhat optimistic that insurance coverage will be increasing in 2022 for 18F-PSMA/PYL PET imaging, as well as increased access within reasonable distances. Meanwhile the Auxmin scans are available and should be used before scheduling either lymph node surgery or blind whole-pelvic radiation.
Dale:
Very similar radiation dose as in ASCENDE-RT. ASCENDE-RT gave 9 months of ADT vs 2 years here. Standard-of-care ADT duration with brachy boost is now 18 months based on TROG RADAR 03.04.
Jon-
Almost all patients in this trial received the PSMA PET scan to rule out any visible tumors. The entire point here is that you have to treat what you can’t see, or as you say “blind.”
Jon:
Regrettably, the Axumin scans are only approved for use in men with recurrence of prostate cancer after first-line treatment.
Similarly, the Pylarify scans are only approved for use in men with (a) suspected metastasis who are candidates for initial definitive
therapy; (b) suspected recurrence based on elevated PSA level.
This leaves insurance providers with a lot of leeway to NOT approve use of these scans in men suspected of high-risk prostate cancer with positive lymph nodes who need first-line treatment.
The gallium-67 PSMA scans, by contrast, are approved for use in patients who are seeking first-line treatment.
Sitemaster:
Pylarify was FDA-approved based on two Phase III trials. The CONDOR trial was for recurrent patients. The OSPREY trial was for high-risk patients (Cohort A) and patients newly-diagnosed with metastases using other imaging (Cohort B). They used the NCCN definition of high-risk: “clinical stage ≥T3a or PSA >20 ng/mL or Gleason score ≥8.”
Medicare and insurance have not yet agreed to cover either radioindicator – it usually takes about 6 months after FDA approval. I’ve heard that when they approve it, Medicare will reimburse patients who’ve paid out-of-pocket since FDA approval, but patients should check with CMS.
I hope these PSMA PET/CTs will replace bone scan/CTs for ruling out distant metastases. What scares me is if patients will wait until lymph node metastases show up on these scans before getting WPRT, and it will be too late to cure.
Allen:
The FDA-approved indications for Pylarify are very specific in the use of the term “metastasis”. My point is that the term “metastasis” is no longer very rigorous. It used to clearly mean metastasis visible on a bone scan or a CT scan (M1 disease). It used to NOT mean nodal or other metastasis (N1 or M0 disease). Exactly what it means in the context of coverage of Pylarify PET/CT scans is going to be an interesting case example in the evolution of the use of the term … to be determined (to a large extent) by CMS!