Confirming and Refining Our Existing Postoperative Treatment Strategies Through the Use of Novel Prostate-Specific Positron Emission Tomography (PET) Imaging

For years, our treatment volumes for radiation therapy have been empirically informed by consensus statements of experienced radiation oncology research groups.1Michalski JM Lawton C El Naqa I et al.Development of RTOG consensus guidelines for the definition of the clinical target volume for postoperative conformal radiation therapy for prostate cancer.Int J Radiat Oncol Biol Phys. 2010; 76: 361-368Abstract Full Text Full Text PDF PubMed Scopus (281) Google Scholar, 2Hall WA Paulson E Davis BJ et al.NRG Oncology updated international consensus atlas on pelvic lymph node volumes for intact and postoperative prostate cancer.Int J Radiat Oncol Biol Phys. 2021; 109: 174-185Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 3Robin S Jolicoeur M Palumbo S et al.Prostate bed delineation guidelines for postoperative radiation therapy: On behalf of The Francophone Group of Urological Radiation Therapy.Int J Radiat Oncol Biol Phys. 2021; 109: 1243-1253Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar, 4Sidhom MA Kneebone AB Lehman M et al.Post-prostatectomy radiation therapy: Consensus guidelines of the Australian and New Zealand Radiation Oncology Genito-Urinary Group.Radiother Oncol. 2008; 88: 10-19Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar Global radiation oncology collaborations have embarked upon these efforts with the goal of standardizing, in an evidence-based fashion, radiation oncology clinical practice. Such recommendations frequently serve as guidelines for ensuring uniformity in prospective clinical trials. Residents and trainees follow these recommendations when learning how to delineate radiation therapy volumes. Such contouring consensus statements are typically informed by published patterns of recurrence. These data are then used in contouring recommendations. In prostate cancer, these treatment volume recommendations are being completely re-evaluated with the introduction of novel prostate cancer-specific imaging technologies, such as Prostate-Specific Membrane Antigen Positron Emission Tomography scanning. Radiation therapy as a modality is perfectly positioned to leverage these data, as we can appropriately adjust our volumes to account for such recurrence patterns. In the article by Horsley et al, the authors present outcomes from over 1000 Prostate-Specific Membrane Antigen Positron Emission Tomography scans with over 140 local recurrences that were meticulously identified by a multidisciplinary team. Patients who developed recurrences had not been previously treated with radiation therapy. These local recurrences were mapped as to their precise proximity to predefined reference points. The distribution of these recurrences was subsequently compared with currently published consensus statements on postoperative prostate bed radiation volumes. Specific consensus statements to which this was compared included that of the Radiation Therapy Oncology Group (RTOG) along with the Faculty of Radiation Oncology Genito-Urinary Group.1Michalski JM Lawton C El Naqa I et al.Development of RTOG consensus guidelines for the definition of the clinical target volume for postoperative conformal radiation therapy for prostate cancer.Int J Radiat Oncol Biol Phys. 2010; 76: 361-368Abstract Full Text Full Text PDF PubMed Scopus (281) Google Scholar,4Sidhom MA Kneebone AB Lehman M et al.Post-prostatectomy radiation therapy: Consensus guidelines of the Australian and New Zealand Radiation Oncology Genito-Urinary Group.Radiother Oncol. 2008; 88: 10-19Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar This revealed that the existing RTOG prostate bed atlas provided over 98% coverage of these recurrences and the Faculty of Radiation Oncology Genito-Urinary Group atlas over 90% coverage. The authors are to be commended for a truly exceptional amount of work in mapping these recurrences. Moreover, it's reassuring that both widely referenced and utilized atlases performed well. Regarding specific practice implications and future directions from these results, there are several. First, careful attention should be given to the posterior lateral recesses of the clinical target volume on either side of the rectum as a high volume of recurrences occurred in these areas; this is a common region over which contours are adjusted with a goal of dosimetrically sparing the rectum. This consideration must be carefully balanced by the radiation oncologist to ensure that established dosimetric constraints for the rectum are still respected. Second, there were few recurrences anteriorly, in the region posterior to the pubic symphysis. Enthusiasm to de-escalate dose to this region may be low given that covering the region does not typically affect critical organ at risk doses, yet it certainly represents an optimal candidate area for dose to be reduced possibly to avoid pubic bone fractures. The standard postoperative radiation timing for patients with adverse pathologic features has now shifted to early salvage therapy rather than adjuvant.5Vale CL Fisher D Kneebone A et al.Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: A prospectively planned systematic review and meta-analysis of aggregate data.Lancet. 2020; 396: 1422-1431Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar Embracing novel PET data is clearly the wave of the future for the specialty of radiation oncology, and this can be easily acquired and applied in the salvage setting. Careful attention to using this rapidly expanding clinical tool is warranted. Radiation oncologists should be very familiar with using the PET scan, specifically registering the scan to a computed tomography and magnetic resonance simulation images for treatment planning. Although expected patterns of recurrence are helpful, individual patient PET-based recurrences (if visualized) are even more so. The clear benefits of using PET in this manner were recently demonstrated by the 18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer trial, which showed that the inclusion of prostate-specific PET scanning improved freedom from biochemical recurrence.6Jani AB Schreibmann E Goyal S et al.(18)F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): A single centre, open-label, phase 2/3 randomised controlled trial.Lancet. 2021; 397: 1895-1904Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar Considering that using PET in 18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer showed the benefit of including PET information in the treatment planning process, when available, acquisition and application of PET data should be considered a current standard for postoperative radiation therapy. Supplementing PET imaging with known regions of high risk will likely further improve outcomes. When PET-based evidence of recurrence location is not available, or PET scanning is not approved, then using the knowledge of high-risk regions from series such as the one presented by Horsley et al provides a useful strategy to inform radiation oncologists as to locations that require careful attention for coverage. In summary, this well-conducted series by Horsley et al clearly shows that certain high-risk areas, specifically the posterior lateral rectal recess (along with others more centrally), are critical to include and may be at high risk of recurrence postoperatively. Given the presence of recurrences in these regions (that were nicely encompassed over 98% of the time in the RTOG atlas), continuing to use this atlas in the future may be an excellent strategy going forward. Conducting carefully designed patterns of recurrence analyses using large prostate cancer- specific novel imaging data is very important to constantly refining and informing strategies to improve the outcomes of patients treated with radiation therapy for prostate cancer in the postoperative setting. Mapping of Local Recurrences After Radical Prostatectomy Using 68-Gallium–Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography: Implications for Postprostatectomy Radiation Therapy Clinical Target VolumesInternational Journal of Radiation Oncology, Biology, PhysicsVol. 115Issue 1PreviewOur objective is to describe the distribution of local recurrences after radical prostatectomy (RP) as delineated using 68-Gallium–prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) to identify areas where current consensus guideline clinical target volumes (CTVs) are insufficient or excessive and to identify predictors of recurrence location within the fossa. Full-Text PDF