Role of 68-Ga-PSMA-PET/CT in Pelvic Radiotherapy Field Definitions for Lymph Node Coverage in Prostate Cancer Patients - Beyond the Abstract

Lymph node metastasis is observed in approximately 1/3 of patients with intermediate- to high-risk prostate cancer patients. There is a debate in the pelvic nodal irradiation in this group of patients. Although randomized trials demonstrated no benefit of pelvic nodal irradiation,1-3 some retrospective series have found pelvic field irradiation to be beneficial.4-6 After a technical analysis of the randomized trials with no benefit of pelvic nodal irradiation, it was clearly demonstrated that the lack of benefit is mainly due to lack of inadequate lymphatic coverage.


In the GETUG trial;3 the pelvic clinical target volume included the distal common iliac, internal iliac, external iliac, and obturator nodes, and the cranial border crosses the internal and external iliac junction located at S1/S2. According to the RTOG guideline;2 the superior border of the pelvic field was the L5/S1 interspace. However, in both of these studies, common iliac lymph nodes were not totally included. Previous studies reported that approximately 50% of recurrences after prostate radiotherapy or radical prostatectomy lie mostly in the common iliac lymph nodes.

With the increasing use of functional imaging in prostate cancer, the rate of detecting lymph nodes and distant metastases increased with 68Ga-PSMA-PET/CT compared to conventional imaging modalities and other PET tracers. There is limited data for use of 68Ga-PSMA-PET/CT in radiotherapy decisions and radiation field arrangements in prostate cancer patients treated with definitive radiotherapy. We recently demonstrated that after 68Ga-PSMA-PET/CT, 12% change in the patient risk group, 28% change in tumor stage, and 13% modification of RT were observed.7

In this current study,8, 9 we aimed to examine whether PSMA-positive LNs are located within the three different pelvic fields defined by the Genitourinary Group (GETUG) trial,3 the Radiation Therapy Oncology Group (RTOG) guidelines,2 and the pelvic field extending superiorly from L4/L5 used in the ongoing trial RTOG 0924 (NCT01368588).

A total of 138 patients with 441 PSMA-positive lymph node metastasis were analyzed. Two different analyses were performed those with pelvic only lymph node metastasis and those with pelvic and paraaortic lymph node metastases. The field defined in the GETUG trial encompassed 44.2% and 51.7% of patients with pelvic and paraaortic lymph node metastasis and pelvic only lymph node metastasis, respectively. The lymph node coverage rates were 52.2% and 61.0% according to fields defined by ROG guidelines. Extending the cranial margin of the pelvic field from L5/S1 to L4/L5 improves the accuracy of pelvic field irradiation in approximately 20% of patients (71.0% and 83.1%).

The lymph nodes that were not included in all three pelvic fields were para-aortic and perirectal lymph nodes. The risk of paraaortic and perirectal lymph node metastasis is closely related to the number of lymph node metastases. The current international guidelines and previously defined pelvic fields are insufficient for covering all PSMA-positive lymph nodes.

The conclusions of this study are preliminary and 68Ga-PSMA-PET/CT is not widely accepted as a routine imaging modality for prostate cancer staging, long-term prospective studies are needed to confirm our findings and assess the outcomes of 68Ga-PSMA-PET/CT-based lymphatic irradiation in clinical practice.

In this study the irradiation fields were arranged according to 68Ga-PSMA-PET/CT findings. Therefore, the clinical results of this study will enlighten the future perspective of 68Ga-PSMA-PET/CT during prostate cancer radiotherapy.

Written by: Cem Önal, MD, Department of Radiation Oncology, Adana Dr. Turgut Noyan Research and Treatment Center, Baskent University Faculty of Medicine, Adana, Turkey

References:

  1. Asbell SO, Krall JM, Pilepich MV, et al. Elective pelvic irradiation in stage A2, B carcinoma of the prostate: analysis of RTOG 77-06. Int J Radiat Oncol Biol Phys. 1988;15:1307-1316.
  2. Lawton CA, DeSilvio M, Roach M, 3rd, et al. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys. 2007;69:646-655.
  3. Pommier P, Chabaud S, Lagrange JL, et al. Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01. J Clin Oncol. 2007;25:5366-5373.
  4. Aizer AA, Yu JB, McKeon AM, et al. Whole pelvic radiotherapy versus prostate only radiotherapy in the management of locally advanced or aggressive prostate adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009;75:1344-1349.
  5. Mantini G, Tagliaferri L, Mattiucci GC, et al. Effect of whole pelvic radiotherapy for patients with locally advanced prostate cancer treated with radiotherapy and long-term androgen deprivation therapy. Int J Radiat Oncol Biol Phys. 2011;81:e721-726.
  6. Milecki P, Baczyk M, Skowronek J, et al. Benefit of whole pelvic radiotherapy combined with neoadjuvant androgen deprivation for the high-risk prostate cancer. J Biomed Biotechnol. 2009;2009:625394.
  7. Onal C, Torun N, Akyol F, et al. Integration of 68Ga-PSMA-PET/CT in Radiotherapy Planning for Prostate Cancer Patients. Clin Nucl Med. 2019;44:e510-e516.
  8. Onal C. In response to Goyal et al. Radiother Oncol. 2020.
  9. Onal C, Ozyigit G, Guler OC, et al. Role of 68-Ga-PSMA-PET/CT in pelvic radiotherapy field definitions for lymph node coverage in prostate cancer patients. Radiother Oncol. 2020;151:222-227.
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