Potential impact of 68Ga-PSMA-11 PET/CT on the planning of definitive radiation therapy for prostate cancer

Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate-specific membrane antigen (PSMA) PET/CT detects PCa metastasis with superior accuracy, having a potential impact on the planning of definitive radiation therapy (RT) for nonmetastatic PCa. Our objectives were to determine how often definitive RT planning based on standard target volumes covers 68Ga-PSMA-11 PET/CT-defined disease and to assess the potential impact of 68Ga-PSMA-11 PET/CT on definitive RT planning. Methods: This was a post hoc analysis of an intention-totreat population of 73 patients with localized PCa without prior local therapy who underwent 68Ga-PSMA PET/CT for initial staging as part of an investigational new drug trial. Eleven of the 73 were intermediate- risk (15%), 33 were high-risk (45%), 22 were very-highrisk (30%), and 7 were N1 (9.5%). Clinical target volumes (CTVs), which included the prostate, seminal vesicles, and (in accord with the Radiation Therapy Oncology Group consensus guidelines) pelvic lymph nodes (LNs), were contoured on the CT portion of the PET/CT images by a radiation oncologist masked to the PET findings. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68Ga-PSMA-11-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had one or more 68Ga-PSMA-11-positive primary prostate lesions. Twenty-five (34%) and 7 (9.5%) of the 73 patients had 68Ga-PSMA- 11-positive pelvic LN and distant metastases, respectively. The sites of LN metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper diaphragm (4%), and presacral (1.5%). The median size of the LN lesions was 6 mm (range, 4-24 mm). RT planning based on the CTVs covered 69 (94.5%) of the 73 primary lesions and 20 (80%) of the 25 pelvic LN lesions, on a per-patient analysis. Conclusion: 68Ga-PSMA-11 PET/CT had a major impact on intended definitive RT planning for PCa in 12 (16.5%) of the 73 patients whose RT fields covered the prostate, seminal vesicles, and pelvic LNs and in 25 (37%) of the 66 patients whose RT fields covered the prostate and seminal vesicles but not the pelvic LNs

Metastasis-free survival and patterns of distant metastatic disease after PSMA-PET-guided salvage radiotherapy in recurrent or persistent prostate cancer after prostatectomy.

INTRODUCTION: Prostate specific membrane antigen positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) in prostate cancer (PCa) patients with biochemical recurrence/persistence after prostatectomy. This work examines (i) metastasis-free survival (MFS) following PSMA-PET guided sRT and (ii) the metastatic patterns on PSMA-PET images after sRT. METHODS: This retrospective, multicenter (9 centers, 5 countries) study included patients referred for PSMA-PET due to recurrent/persistent disease after prostatectomy. Patients with distant metastases (DM) on PSMA-PET prior to sRT were excluded. Cox-regression was performed to assess the impact of clinical parameters on MFS. The distribution of PSMA-PET detected DM following sRT and their respective risk factors were analysed. RESULTS: All (n=815) patients received intensity-modulated RT to the prostatic fossa. In case of PET-positive pelvic lymph nodes (PLN-PET, n=275, 34%), pelvic lymphatics had been irradiated. Androgen deprivation therapy had been given in 251 (31%) patients. The median follow-up after sRT was 36 months. The 2-/4-year MFS following sRT were 93%/81%. In multivariate analysis the presence of PLN-PET was a strong predictor for MFS (HR=2.39, p<0.001). Following sRT, DM were detected by PSMA-PET in 128/198 (65%) patients and two metastatic patterns were observed: 43% had DM in sub diaphragmatic paraaortic LNs (abdominal-lymphatic) whereas 45% in bones, 9% in supra diaphragmatic LNs and 6% in visceral organs (distant). Two distinct signatures with risk factors for each pattern were identified. CONCLUSION: MFS in our study is lower compared to previous studies, obviously due to the higher detection rate of DM in PSMA-PET after sRT. Thus, it remains unclear whether MFS is a surrogate endpoint for overall survival in PSMA PET-staged patients in the post sRT setting. PLN-PET may be proposed as a new surrogate parameter predictive of MFS. Analysis of recurrence patterns in PET after sRT revealed risk factor signatures for two metastatic patterns (abdominal-lymphatic and distant), which may allow individualized sRT concepts in the future

Value of PET imaging for radiation therapy.

This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality