Management Strategy of High-Risk Localized Prostate Cancer: Is there a Transatlantic Consensus?
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Management Strategy of High-Risk Localized
Prostate Cancer: Is there a Transatlantic
Consensus?
Yazid Belkacemi, MD, PhD),y, Gabriele Coraggio, MD),
and Gokoulakrichenane Loganadane, MD),y on behalf of the Transatlantic
Radiation Oncology Network (TRONE)
)AP-HP, Department of Radiation Oncology and Henri Mondor Breast Center, University of Paris-Est (UPEC), Créteil,
France; and yINSERM Unit 955, Team 21, IMRB, University of Paris-Est (UPEC), Créteil, France
Case Presentation
A 70-year-old male patient with neither significant comorbidities nor symptoms was referred to our department for prostate
cancer radiation therapy. The last prostate-specific antigen value was 30 ng/mL. Transrectal ultrasound guided biopsy findings
confirmed the presence of prostatic adenocarcinoma without neuroendocrine component in 11 out of 12 cores, with the
following distribution: in 3 of 3 cores in the right lobe, Gleason score (GS) was 7(4 + 3); in the left lobe, 5 cores corresponded
to GS 7 (4 + 3), 2 cores were GS 8(4 + 4), and 1 was GS 7(3 + 4). There was no sign of extracaspular extension but there was
print & web 4C=FPO
Fig. 1. MRI of prostate showing invasion of posterior aspect of the left lobe (T2, diffusion and perfusion, respectively)
Int J Radiation Oncol Biol Phys, Vol. 110, No. 3, 631e632, 2021
0360-3016/$ - see front matter Ó 2021 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ijrobp.2021.03.012632 Gray Zone International Journal of Radiation Oncology Biology Physics the presence of perineural invasion. Digital rectal examination revealed an asymmetrical prostatic gland without induration or nodules. The bone scan and computed tomography (CT) scan showed no evidence of locoregional or distant disease. The clinical TNM stage was T2cN0M0. Multiparametric prostate magnetic resonance imaging (T2, diffusion, perfusion) showed an invasion of the whole left lobe, especially involving the peripheral zone without extracapsular extension and without seminal vesicle involvement. Magnetic resonance imaging of the prostate showed invasion of the left lobe. Questions 1. Do you recommend positron emission tomography-CT (choline or prostate-specific membrane antigen) in this case instead of standard CT and bone? 2. Would you consider pelvic irradiation? If yes, what would you use for the upper limit of the fields? 3. Would you consider hypofractionation? If yes, what fractionation would you use for the prostate with or without pelvic nodal irradiation? 4. What duration of androgen deprivation therapy would you recommend? See expert opinions on page 633. What would you do? Follow the discussion on Twitter at #gyzone, and take the poll at www.redjournal.org/poll. NotedCME is available for this feature as an ASTRO member benefit, to access visit https://academy.astro.org. Corresponding author: Yazid Belkacemi, MD, PhD; E-mail: yazid.belkacemi@aphp.fr Disclosures: none.
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GRAY ZONE EXPERT OPINIONS
A Trans-Atlantic Voyage of versus IMRT plus brachytherapy were w60% versus
Extended ADT With Local 80%. Most patients, if counseled regarding these out-
comes, would likely choose combination therapy.
Radiation Although the trial did show higher toxicity rates with
brachytherapy, this is likely technique related.
This is a patient with likely >10-year life expectancy with Eighteen months. In the PCS-IV trial,3 18 versus 36
high-volume1 (11 of 12 cores) high-risk (Gleason 8, pros- months of ADT had overlapping overall survival curves
tate-specific antigen 30) prostate cancer, and therefore through 10 years and beyond. Although the ASCENDE-
aggressive treatment with curative intent is warranted. RT trial did use 12 months of ADT for both arms,
duration of ADT was not the study question, so that trial
I hope that soon, we will be able to recommend positron could not demonstrate whether 12 months was the
emission tomography (PET)ecomputed tomography optimal duration.
(CT) for the initial staging of high-risk prostate cancer.
Choline PET and fluciclovine PET, both approved by the
US Food and Drug Administration (FDA), are more Ronald C. Chen, MD, MPH
Department of Radiation Oncology
sensitive than conventional imaging (CT, magnetic reso-
University of Kansas Cancer Center
nance imaging, bone scan) at detecting prostate cancer. Kansas City, Kansas
However, in the United States, these scans are mostly
limited to recurrence disease. Prostate-specific membrane Disclosures: Dr Chen reports personal fees from Myovant, Abbvie,
antigen-PET has just been FDA approved, but insurance Accuray, and Blue Earth, outside the submitted work.
denials remain the major barrier to patients having access
to these scans.
I do not recommend elective pelvic irradiation. Although References
a portion of high-risk patients have microscopic nodal
disease, this alone does not prove that irradiating the 1. Belkacemi Y, Coraggio G, Loganadane G. Management Strategy of
pelvis will cure more patients. RTOG 7706, GETUG-01, High-Risk Localized Prostate Cancer: Is there a Transatlantic
and RTOG 9413 are 3 randomized trials that showed no Consensus? Int J Radiat Oncol Biol Phys 2021;110:631-632.
benefit from pelvic irradiation. RTOG 9413, a 2 2 trial 2. Morris WJ, Tyldesley S, Rodda S, et al. Androgen suppression com-
bined with elective nodal and dose escalated radiation therapy (the
that randomized patients to neoadjuvant versus adjuvant ASCENDE-RT trial): An analysis of survival endpoints for a random-
androgen deprivation therapy (ADT) and pelvic versus ized trial comparing a low-dose-rate brachytherapy boost to a dose-
prostate-only radiation, showed that prostate-only radia- escalated external beam boost for high- and intermediate-risk prostate
tion plus adjuvant ADT had the best 10-year progression- cancer. Int J Radiat Oncol Biol Phys 2017;98:275-285.
3. Nabid A, Carrier N, Martin AG, et al. Duration of androgen deprivation
free survival rates.
therapy in high-risk prostate cancer: A randomized phase III trial. Eur
I strongly recommend intensity-modulated radiation Urol 2018;74:432-441.
therapy (IMRT) plus brachytherapy. In the ASCENDE-
RT trial,2 the 9-year recurrence-free survival rates for
high-risk patients randomized to dose-escalated IMRT https://doi.org/10.1016/j.ijrobp.2020.11.032
What would you do? Continue the discussion on Twitter at #gyzone, and take the poll at www.redjournal.org/poll.
Int J Radiation Oncol Biol Phys, Vol. 110, No. 3, 633e635, 2021
0360-3016/$ - see front matter Ó 2020 Elsevier Inc. All rights reserved.634 Gray Zone Expert Opinions International Journal of Radiation Oncology Biology Physics
Ashesh B. Jani, MD, MSEE, FASTRO
Department of Radiation Oncology
Follow the Trials Winship Cancer Institute of Emory University
Atlanta, Georgia
1. On the western side of the Atlantic, conventional im- Disclosures: None.
aging1 remains standard of care (eg, magnetic resonance
imaging or computed tomography of the abdomen/
pelvis, bone scan). Although prostate-specific mem- References
brane antigen positron emission tomography is not yet
FDA approved for primary high-risk prostate cancer, 1. Belkacemi Y, Coraggio G, Loganadane G. Management Strategy of
High-Risk Localized Prostate Cancer: Is there a Transatlantic
approval could happen soon. Positron emission tomog-
Consensus? Int J Radiat Oncol Biol Phys 2021;110:631-632.
raphy (choline, prostate-specific membrane antigen, or 2. Hall WA, Paulson E, Davis BJ, et al. NRG Oncology updated inter-
fluciclovine) can be performed where available under national consensus atlas on pelvic lymph node volumes for intact and
local investigational new drug/protocol, and it can assist postoperative prostate cancer. Int J Radiat Oncol Biol Phys 2021;109:
in staging owing to its high diagnostic yield. 174-185.
3. Morgan SC, Hoffman K, Loblaw DA, et al. Hypofractionated radiation
2. RTOG 9413 found that neoadjuvant androgen depriva-
therapy for localized prostate cancer: Executive summary of an
tion therapy (ADT) plus pelvic radiation therapy arm ASTRO, ASCO, and AUA evidence-based guideline. Pract Radiat
initially had the best results (of 4 arms studied) with Oncol 2018;8:354-360.
later convergence. Results of RTOG 0924, which stud-
ied pelvic radiation therapy with modern radiation
therapy doses, are pending. In this particular patient, https://doi.org/10.1016/j.ijrobp.2020.11.062
although difficult to quantify (not many patients with his
exact features are included in the Partin tables and
related nomograms), he has a high risk of occult lymph
node involvement on the basis of high prostate-specific Treating Localized High-Risk
antigen, high-volume disease, and digital rectal exam Prostate Cancer: Do All Roads
findings. I would recommend pelvic nodal irradiation;
Lead to Rome?
the superior border would be at L4-L5, per the new atlas
guidelines.2
3. Moderate hypofractionation (2.4-3.4 Gy per fraction to The proPSMA study has recently shown the superiority of
the prostate) has supporting data for low-, intermediate-, PSMA positron emission tomography (PET) to conven-
and now high-risk disease,3 although treatment of nodes tional imaging in detecting lymph nodes and distant dis-
in this context remains less clear. Simultaneous inte- ease in patients with high-risk prostate cancer.1
grated boost technique to the prostate and nodes in 20 to Accordingly, we have been using PSMA PET imaging
28 fractions may be considered. for initial staging of patients with high-risk prostate can-
4. The RTOG/NRG standard is 2 years of ADT; however, cer whenever possible. Notably, in our experience, PSMA
18 months can be considered on the basis of randomized PET is not widely covered by insurance companies in the
data comparing 18 versus 36 months. Duration should initial staging.
be tailored to tolerance of ADT-related adverse effects. As we await the results of Radiation Therapy Oncology
NRG Oncology/GU-009 will be studying systemic Group study 0924, we may consider omitting pelvic lymph
therapy intensification and deintensification based on node irradiation in this man with high-risk prostate cancer
genomic score. unless PSMA PET is positive for pelvic lymph nodes.2 We
What would you do? Follow the discussion on Twitter at #gyzone, and take the poll at www.redjournal.org/poll.Volume 110 Number 3 2021 Gray Zone Expert Opinions 635
acknowledge that irradiating the pelvis is also a reasonable Disclosures: none.
approach. When we treat the pelvis, we limit the upper
border to L4-5 or the aortic bifurcation.
When treating prostate only without high-dose-rate References
brachytherapy boost, we use moderate hypofractionation in
20 fractions to the prostate (60 Gy). If irradiating the pelvis, 1. Hofman MS, Lawrentschuk N, Francis RJ, et al. Prostate-specific
we use 28 fractions (70 Gy) to the prostate, and the elective membrane antigen PET-CT in patients with high-risk prostate cancer
nodal volume receives 45 Gy in the first 25 fractions. In before curative-intent surgery or radiotherapy (proPSMA): A pro-
spective, randomised, multicentre study. Lancet 2020;395:1208-1216.
practice, we would argue for brachytherapy boost (high 2. Belkacemi Y, Coraggio G, Loganadane G. Management Strategy of
dose rate, 15 Gy, single fraction) with 25 fractions of High-Risk Localized Prostate Cancer: Is there a Transatlantic
external beam radiation therapy (45 Gy) and 18 months of Consensus? Int J Radiat Oncol Biol Phys 2021;110:631-632.
androgen deprivation therapy as supported by the Tasman 3. Denham JW, Joseph D, Lamb DS, et al. Short-term androgen suppres-
Radiation Oncology Group’s RADAR study.3 sion and radiotherapy versus intermediate-term androgen suppression
and radiotherapy, with or without zoledronic acid, in men with locally
advanced prostate cancer (TROG 03.04 RADAR): An open-label,
Osama Mohamad, MD, PhD randomised, phase 3 factorial trial. Lancet Oncol 2014;15:1076-1089.
Felix Feng, MD
Department of Radiation Oncology, University of California San
Francisco, San Francisco, California https://doi.org/10.1016/j.ijrobp.2021.03.020
What would you do? Follow the discussion on Twitter at #gyzone, and take the poll at www.redjournal.org/poll.You can also read
