For the majority of patients at high-risk for biochemical recurrence of prostate cancer (PCa), new prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) research reaffirms a lack of sustained efficacy for monotherapy treatment with local radiation therapy or radical prostatectomy.
For the retrospective study, recently published in BJUI Compass, researchers reviewed PSMA PET/CT data for 145 patients who underwent local radiation therapy (RT) (42 patients), radical prostatectomy (RP) (77 patients) or both (26 patients) for PCa. All patients in the cohort were deemed to be at high-risk for biochemical recurrence (PSA > 2 ng/ml above nadir after RT or > 1 ng/ml after RP), according to the study.
The study authors found that 77 percent of the cohort (113 patients) had one or more prostate lesions on PSMA PET/CT. While 32 patients (28.3 percent) had > three prostate lesions, the researchers noted that 21 patients (18.6 percent) had oligometastatic disease (one to three lesions), 31 patients (27.4 percent) had lesions consistent with N1MO disease and 29 patients (25.7 percent) had lesions isolated to the prostate or prostate bed.
“Overall, based on PSMA PET/CT findings in this study, up to 55% of patients could have delayed or avoided intensified systemic therapy and its potential side effects with alternative treatment options,” wrote lead study author Nicole Handa, M.D., who is associated with the Feinberg School of Medicine at Northwestern University in Chicago, and colleagues.
Multivariable analysis revealed that a combination of RP and PT was associated with a 69 percent lower risk of positive findings on PSMA PET/CT in contrast to a nine percent lower risk with monotherapy use of local RT or RP.
(Editor's note: For additional content on prostate cancer imaging, click here.)
“In combination, RP plus RT may work to decrease any micro-metastatic disease that is present at the time of initial treatment. However, this intensified adjuvant therapy is often reserved for those with very high-risk features at the time of initial diagnosis, as combination RP with RT is associated with an increased risk of urinary incontinence (and) bladder neck contractures. On the other hand, salvage RT for patients with a rise in PSA after RT may be curative if initiated early,” pointed out Handa and colleagues.
While the researchers saw no significant difference between the treatment groups with respect to distant metastasis, they noted that initial treatment strategies were associated with differences in local PCa recurrence and nodal recurrence.
Three Key Takeaways
1. Limited efficacy of monotherapy. Monotherapy with either local radiation therapy (RT) or radical prostatectomy (RP) shows limited sustained efficacy for high-risk prostate cancer patients, reinforcing the need to reassess initial treatment strategies.
2. Benefit of combined RP and RT. Combining RP and RT was associated with a significantly lower risk (69 percent) of positive PSMA PET/CT findings in comparison to monotherapy with RP or RT (9 percent), suggesting improved control of micro-metastatic disease compared to monotherapy.
3. PSMA PET/CT-guided treatment optimization. PSMA PET/CT imaging allowed for better stratification of disease, potentially enabling up to 55 percent of patients to avoid or delay systemic therapy with alternative, targeted non-systemic treatments.
Patients who had RT were 4.5 times more likely to have a localized PCa recurrence in comparison to those who had RP, according to the study authors. The researchers also found that patients who had RT and those who had combination RT/RP were 92 percent and 80 percent less likely, respectively, to have nodal recurrence in comparison to patients with a RP.
The study authors emphasized non-systemic therapies for patients with localized or regional nodal recurrence.
“Treatment options for these patients include salvage RP, RT, selective node dissection, ablative therapy or focal brachytherapy,” noted Handa and colleagues.
(Editor’s note: For related content, see “PSMA PET/CT Study Shows Mixed Results with Single Metastasis-Directed Radiotherapy for Oligometastatic PCa,” “Study Shows No Impact of Hormone Therapy on PET/CT with 18F-Piflufolastat in PCa Imaging” and “Emerging PET/CT Agent Shows Promise in Detecting PCa Recurrence in Patients with Low PSA Levels.”)
Beyond the inherent limitations of a single-center retrospective study, the authors acknowledged a relatively high cutoff for PSA (> 1 ng/ml) for patients who had a RP. The researchers also noted a lack of complete data for referred patients, who had initial workup and treatment at other facilities.
