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Our objectives were (i) to assess the prevalence of metastatic PCa in patients with biochemical failure following RP and PSA levels\u2009\u2264\u20091 ng\/mL, as detected by\n                      <jats:sup>18<\/jats:sup>\n                      F-PSMA-1007 PET\/CT (PSMA-PET), and (ii) to identify predictors of metastatic disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fifty-five patients with biochemical recurrence (BCR,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200947) or persistent disease (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098) following RP as their primary and only prior treatment were retrospectively included if presenting with PSA levels\u2009\u2264\u20091 ng\/mL. Patients who received any other anticancer treatment were excluded. PSMA-PET findings were categorized as either local recurrence (i.e., prostatic fossa and seminal vesicles) or metastases. Predictors of PSMA-PET positivity were assessed with univariate and multivariate regression analyses both in the whole sample and in two subgroups defined according to PSA levels (Group A\u2009=\u2009PSA\u2009&lt;\u20090.5 ng\/mL; Group B\u2009=\u2009PSA between 0.5 and 1 ng\/mL).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median PSA at the time of PET\/CT was 0.37 ng\/mL (range: 0.13\u20131.0). PSMA-PET was positive in 22\/55 (40%) patients, 14\/55 (25%) patients had metastatic disease. Overall, 31 PSMA-positive lesions were identified: 12\/31 (39%) and 19\/31 (61%) were local recurrences and metastases, respectively. In the whole cohort, ISUP grade\u2009&gt;\u20093 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003), pN1 status after surgery (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011), time to BCR\u2009\u2264\u200926 months (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03), and persistent disease (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003) were significantly associated with a higher rate of PSMA-positive metastases. At multivariate analysis, ISUP grade\u2009&gt;\u20093 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016) was the only independent predictor of metastases. Metastatic disease was detected in 8\/38 (21%) patients in Group A and in 6\/17 (35%) patients in Group B, respectively. In Group A, pN1 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.043) and persistent disease (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040) were significant predictors of metastases. In Group B, ISUP grade\u2009&gt;\u20093 was the only predictor (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.028).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ISUP grade\u2009&gt;\u20093, time to BCR\u2009\u2264\u200926 months, pN1 status, and persistent disease after surgery indicated a higher likelihood of PSMA-positive metastatic disease in a homogeneous cohort of patients with biochemical failure and low PSA values. pN1 status and persistent disease were significant predictors of metastatic disease also in patients with PSA levels\u2009&lt;\u20090.5 ng\/mL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12149-026-02153-9","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:40:24Z","timestamp":1768477224000},"page":"521-531","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biochemical failure after radical prostatectomy with PSA\u2009\u2264\u20091 ng\/mL: prediction of PSMA-positive metastatic disease"],"prefix":"10.1007","volume":"40","author":[{"given":"Giulia","family":"Santo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Rosarno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Restuccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Lucio","family":"Cascini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Grillone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4664-1965","authenticated-orcid":false,"given":"Francesco","family":"Cicone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"2153_CR1","unstructured":"European Commission. 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