The Utility of PET/CT in the Planning of External Radiation Therapy for Prostate Cancer

Abstract

Radiotherapy and radical prostatectomy are the definitive treatment options for patients with localized prostate cancer. A rising level of prostate-specific antigen after radical prostatectomy indicates prostate cancer recurrence, and these patients may still be cured with salvage radiotherapy. To maximize chance for cure, the irradiated volumes should completely encompass the extent of disease. Therefore, accurate estimation of the location of disease is critical for radiotherapy planning in both the definitive and the salvage settings. Current first-line imaging for prostate cancer has limited sensitivity for detection of disease both at initial staging and at biochemical recurrence. Integration of PET into routine evaluation of prostate cancer patients may improve both staging accuracy and radiotherapy planning. ¹⁸F-FDG PET/CT is now routinely used in radiation planning for several cancer types. However, ¹⁸F-FDG PET/CT has low sensitivity for prostate cancer. Additional PET probes evaluated in prostate cancer include ¹⁸F-sodium fluoride, ¹¹C-acetate, ¹¹C- or ¹⁸F-choline, ¹⁸F-fluciclovine, and ⁶⁸Ga- or ¹⁸F-labeled ligands that bind prostate-specific membrane antigen (PSMA). PSMA ligands appear to be the most sensitive and specific but have not yet received Food and Drug Administration New Drug Application approval for use in the United States. Retrospective and prospective investigations suggest a potential major impact of PET/CT on prostate radiation treatment planning. Prospective trials randomizing patients to routine radiotherapy planning versus PET/CT-aided planning may show meaningful clinical outcomes. Prospective clinical trials evaluating the addition of ¹⁸F-fluciclovine PET/CT for planning of salvage radiotherapy with clinical endpoints are under way. Prospective trials evaluating the clinical impact of PSMA PET/CT on prostate radiation planning are indicated.

Keywords: PET/CT; PSMA; prostate cancer; radiation.

FIGURE 1.

CTV contours and organs at risk are contoured by radiation oncologists on dedicated planning CT (CT simulation). (A) CTV for intact (definitive) prostate is prostate gland itself with or without pelvic nodes and seminal vesicles. (B) CTV for SRT includes prostate bed with or without pelvic nodes. CTV is usually drawn in absence of radiographic evidence of recurrent disease. Instead, CTVs are based on consensus guidelines to encompass prostate bed with or without pelvic lymph nodes. The most commonly used external-beam dose-fractionation schedules for definitive prostate radiotherapy deliver 75.6–79.2 Gy in fractions of 1.8–2 Gy, whereas those for SRT deliver 66–72 Gy. When included, pelvic nodal volumes are prescribed 45–50.4 Gy.

FIGURE 2.

⁶⁸Ga-PSMA PET enables identification of areas of gross disease that are missed on CT. Intensity-modulated radiotherapy can be used to deliver higher dose to areas with gross disease. At top is example of SRT plan and dose–volume histogram for patient with rising PSA level after radical prostatectomy planned without radiographic evidence of visible gross disease. Pelvic nodal and prostate bed volumes are prescribed doses of 45 and 72 Gy, respectively. At bottom is example of SRT plan and dose–volume histogram for patient who underwent ⁶⁸Ga-PSMA PET before planning. ⁶⁸Ga-PSMA PET enabled identification of ⁶⁸Ga-PSMA–positive left internal iliac pelvic node. Intensity-modulated radiotherapy was used to focally increase dose to gross disease to beyond 65 Gy while adequately sparing normal organs at risk. Dose-color-wash displays simulate dose on CT simulation scan with color scale of blue (45 Gy) to red (72 Gy). Dose–volume histograms are plotted with bin doses along horizontal axis and percentage of structure that receives dose greater than or equal to that dose on vertical axis. Each line on dose–volume histogram represents a particular volume (e.g., CTV and relevant organs at risk).

FIGURE 3.

Impact of ⁶⁸Ga-PSMA PET/CT on target volumes. Patient with biochemical recurrence (PSA level, 0.81 ng/mL) 1 y after radical prostatectomy (Gleason score, 9) was referred for SRT. ⁶⁸Ga-PSMA PET showed focal ⁶⁸Ga-PSMA uptake in right side of prostate bed (yellow arrows), with nodular tissue-thickening on CT. In addition, ⁶⁸Ga-PSMA PET revealed focal ⁶⁸Ga-PSMA uptake in 2 right perirectal subcentimeter lymph nodes (short axis, 4 mm; red arrows). Perirectal nodes are not covered by standard SRT and would not have been suspected to harbor recurrent disease based on CT. SRT volumes were expanded to encompass perirectal nodal region.

FIGURE 4.

⁶⁸Ga-PSMA PET/CT identified solitary L5 metastasis in patient with recurrent prostate cancer after prostatectomy and PSA level of 1. SBRT was used to deliver 18 Gy in single fraction to solitary metastasis. Dose-color-wash shows that 100% of prescribed dose covered target volume while sparing cauda equine (yellow contours).

FIGURE 5.

Impact of ⁶⁸Ga-PSMA PET/CT on initial management of high-risk prostate cancer. A 77-y-old man with newly diagnosed prostate cancer (initial PSA level, 7.1; Gleason score, 4 + 5 = 9) underwent MRI showing right posterolateral prostate lesion with gross extracapsular extension and right seminal vesicle invasion. Bone scan was negative. ⁶⁸Ga-PSMA PET/CT showed intense ⁶⁸Ga-PSMA uptake in prostate with seminal vesicle invasion (yellow arrows), ⁶⁸Ga-PSMA–positive subcentimeter external iliac lymph nodes (blue arrows), and focal ⁶⁸Ga-PSMA uptake in 2 bone lesions (red arrows). Patient was staged as hormone-sensitive oligometastatic M1b and offered SBRT to 2 bone metastases in addition to radiotherapy to prostate and pelvic nodes with concurrent androgen deprivation therapy.

FIGURE 6.

Patient with biochemical recurrence (PSA level, 1.85 ng/mL) 7 y after radical prostatectomy (Gleason score, 7; pT2c) underwent ⁶⁸Ga-PSMA PET/CT, which showed focal ⁶⁸Ga-PSMA uptake in right side of prostate bed (yellow arrows) and intense focal ⁶⁸Ga-PSMA uptake in proximal portion of left fifth rib (red arrows). Patient was offered metastasis-directed SBRT in addition to SRT to prostate bed and nodes.