Progression of Index Metastases in Oligometastatic Hormone-Sensitive Prostate Cancer: Implications for Metastasis-Directed Therapy?

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Vedang Murthy, Parth Verma, Priyamvada Maitre, Gowtham Surya Krishnasamy, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6740073/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Dec, 2025 Read the published version in Prostate Cancer and Prostatic Diseases → Version 1 posted 10 You are reading this latest preprint version Abstract Background: For de-novo oligometastatic prostate cancer (omHSPC) treated with standard of care androgen suppression and prostate radiotherapy, the patterns of progression vis-a-vis index metastatic sites are not well understood. Methods: This single centre study included patients with de-novo omHSPC (CHAARTED criteria) staged with a PSMA-PET/CT scan at diagnosis, treated with androgen suppression and prostate radiotherapy, and re-staged with PSMA-PET/CT at biochemical progression. Disease status at index oligometastases was noted at progression. Results: From 2015 to 2024, 79 patients with omHSPC were found eligible (M1a = 22, M1b = 57). Over a median follow-up of 39 months (IQR 28-69), 15 patients (19%) had disease progression. Restaging PSMA-PET/CT revealed progression of the index oligometastases for 11/15 patients (73%), with additional metastases in 7 of these. Conclusion: The high proportion of progression at the index oligometastases supports the potential benefit of metastasis-directed therapy for local ablation. Biological sciences/Cancer/Urological cancer/Prostate cancer Health sciences/Diseases/Cancer/Cancer therapy Figures Figure 1 INTRODUCTION De novo oligometastatic hormone sensitive prostate cancer (omHSPC) is typically treated with a combination of lifelong androgen deprivation therapy (ADT), androgen receptor pathway inhibitors (ARPI), and radiotherapy to the prostate. The role of metastasis-directed therapy (MDT) is not established yet. The Advanced Prostate Cancer Consensus Conference (APCCC) 2024 expert panel did not reach consensus on utilisation of MDT for de-novo omHSPC, with only 17% experts favouring MDT based on conventional imaging and 57% voting for additional next-generation imaging before deciding about MDT [ 1 ]. Prostate specific membrane antigen (PSMA) based imaging (such as PSMA-PET/CT) is now preferred for more accurate disease staging and localisation of smaller metastases [ 1 , 2 ]. Currently MDT is not recommended by most global guidelines, and its utilisation is discretionary [ 1 ]. Key trials in omHSPC such as STAMPEDE and PEACE-1 have reported on the benefit of prostate radiotherapy in omHSPC, staged with conventional imaging [ 3 , 4 ]. Details of the patterns of progression are not known, which would help understand the potential role of MDT for the index oligometastases. Therefore, we explored the institutional cohort of PSMA-staged de novo omHSPC treated with ADT and prostate radiotherapy, for sites of disease progression in consideration of the index metastatic lesions. MATERIALS AND METHODS This IRB approved study queried a prospectively maintained database at a large tertiary cancer care centre. We included patients diagnosed with de novo omHSPC, staged with PSMA-PET/CT at diagnosis, and fulfilling the CHAARTED criteria - disease in non-regional lymph nodes or < 5 bone metastases, in the absence of visceral metastases [ 5 ]. All patients were treated with standard of care systemic therapy and radiotherapy to the prostate, without MDT. Follow up was based on PSA, and at biochemical progression all patients underwent a restaging PSMA-PET/CT. Patients with high volume disease, those with castration resistant disease prior to radiotherapy, or those with diagnostic or restaging scan unavailable, were excluded. The individual sites of disease recurrence in the restaging scans were mapped with respect to the index site of metastases in the index scan by nuclear medicine physicians experienced in reporting PSMA-PET/CT. Known prognostic factors - Gleason grade group (4–5 vs 1–3), nodal involvement (N1 vs N0), bone metastases (M1b vs M1a), systemic intensification (intensified ADT vs ADT alone), 6-month nadir PSA ( ≤ 0.1 ng/mL vs higher) - were evaluated for risk of progression of the index metastasis by calculating odds ratio. A p-value of < 0.05 was considered statistically significant. Data was analysed using IBM SPSS v21.0. RESULTS A total of 79 eligible patients treated from January 2015 to January 2024 were included (Table 1 ). Majority (82%) had Gleason grade group 4 or 5 disease. Bony metastases were present in 72% of patients. About 75% received ADT intensified with either ARPI or docetaxel. At a median follow up of 39 months (IQR 28–69), 19% patients (n = 15) had progression. Median time to progression was 28 months (IQR 24–37) from the start of ADT. Restaging PSMA-PET/CT showed visible progression at the index metastases in 11/15 (73.3%) patients. Four patients (26.7%) had progression limited to the index metastatic site only, while 7 (46.6%) showed progression in the index site with new metastatic lesions [Figure 1 ]. None of the prognostic factors showed statistically significant association with progression of index metastases [Table 2 ]. Table 1 Patient demographics n (%) Median PSA (ng/ml, IQR) 32.8 (15.4–79.6) Gleasons group 1 1 (1.5) 2 4 (5) 3 8 (10) 4 27 (34) 5 38 (48) Not known 1 (1.5) cT Stage T2 11 (14) T3a 15 (19) T3b 37 (47) T4a 13 (16) Unknown 3 (4) cN Stage N0 53 (67) N1 26 (33) cM Stage M1a 22 (28) M1b 57 (72) Hormonal Therapy ADT 20 (25.3) ADT + ARPI 47 (59.5) ADT + Docetaxel 11 (13.9) ADT + ARPI + Docetaxel 1 (1.3) Table 2 Univariate analysis for known prognostic factors versus progression of index metastases. Characteristic OR (95% CI) p-value cN0 vs cN1 1.7 (0.1–22.5) 1.0 M1a vs M1b 3.6 (0.3–46.4) 0.6 GS 1–3 vs 4–5 0.3 (0.01–6.4) 0.4 ADT alone vs intensification 1.7 (0.1–22.5) 1.0 6m PSA ≤ 0.1 vs > 0.1 1.1 (0.08–15.5) 1.0 6m PSA ≤ 0.2 vs > 0.2 0.8 (0.08–8.2) 1.0 DISCUSSION To our knowledge, this is the first study to report patterns of recurrence for PSMA-staged omHSPC treated with ADT and prostate radiotherapy without MDT. At progression, restaging PSMA-PET/CT showed progression of index metastases in 75% of the patients, with about a quarter of the patients having progression only at the index site. This suggests a potentially important role of MDT for local control at the site of index oligometastases. Although without robust evidence, the argument in favour of adding MDT to prostate radiotherapy in omHSPC can be threefold. First, very high control rates exceeding 90% have been demonstrated with ablative radiotherapy for metastases, with minimal added toxicities [ 6 – 9 ]. Next line systemic therapy was reported to be safely deferred by using MDT in these non-randomised studies, though PSMA-based imaging was not used. Secondly, there might be a clinical advantage of treating the metastases in the de-novo omHSPC setting rather than metachronous setting, supporting total ablation of visible de novo oligometastases [ 7 ]. Finally, ablation of index lesions in addition to prostate radiotherapy may disrupt polyclonal seeding of further metastases [ 10 ]. Overall, the potential benefit of MDT would likely depend on reliably mapping the oligometastases with PSMA-based imaging, as well as effective ablation of putative hormone-resistant disease in these lesions. Acknowledging the inherent limitations of a small cohort from a single centre, our results are strengthened by PSMA-based staging at diagnosis and recurrence, formal review of all scans by experienced nuclear medicine physicians, and a prospectively maintained database. While the value of MDT is under evaluation by the phase III STAMPEDE-2 randomised trial, this study provides an interesting insight into progression of de novo omHSPC after systemic therapy and prostate only radiotherapy. The high proportion of progression at the index site of metastases (75%), without additional metastases in a third of these, suggests a potential role of ablation of oligometastases to optimize overall disease control. Declarations CONFLICT OF INTEREST: The authors have no conflicts of interest to declare. ETHICS APPROVAL: We confirm that all methods were performed in accordance with the relevant guidelines and regulations. Ethical approval was taken from the Institutional Ethical Committee of Tata Memorial Hospital, Mumbai. No informed consent was taken as Ethics Committee granted wavier. AUTHOR CONTRIBUTIONS: VM conceptualized the study. VM, PM, PV, GSK and NM were involved in patient accrual, data acquisition and study procedures. SC, SG and AA provided technical and material support. PV and PM did statistical analysis. The manuscript was drafted by PV, VM, and PM. All authors approved the final manuscript References Gillessen S, Turco F, Davis ID, Efstathiou JA, Fizazi K, James ND, et al. Management of Patients with Advanced Prostate Cancer. Report from the 2024 Advanced Prostate Cancer Consensus Conference (APCCC). Eur Urol 2025;87:157–216. https://doi.org/10.1016/j.eururo.2024.09.017. Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. The Lancet 2020;395:1208–16. https://doi.org/10.1016/S0140-6736(20)30314-7. Parker CC, James ND, Brawley CD, Clarke NW, Ali A, Amos CL, et al. Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial. PLoS Med 2022;19:e1003998. https://doi.org/10.1371/journal.pmed.1003998. Bossi A, Foulon S, Maldonado X, Sargos P, MacDermott R, Kelly P, et al. Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. The Lancet 2024;404:2065–76. https://doi.org/10.1016/S0140-6736(24)01865-8. Kyriakopoulos CE, Chen Y-H, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J Clin Oncol 2018;36:1080–7. https://doi.org/10.1200/JCO.2017.75.3657. Deodato F, Pezzulla D, Cilla S, Ferro M, Romano C, Bonome P, et al. Stereotactic radiosurgery for bone metastases in oligometastatic prostate cancer patients: DESTROY-2 clinical trial subanalysis. Clin Transl Oncol 2022;24:1177–83. https://doi.org/10.1007/s12094-021-02764-w. Qi X, Li HZ, Gao XS. Radiotherapy of the Primary Tumor and All Metastatic Lesions in Oligometastatic Prostate Cancer: 5-Year Results of Prolong Study. Int J Radiat Oncol 2024;120:S147. https://doi.org/10.1016/j.ijrobp.2024.07.2156. Nickols NG, Tsai S, Kane N, Tran S, Ghayouri L, Diaz-Perez S, et al. Systemic and Tumor-directed Therapy for Oligometastatic Prostate Cancer: The SOLAR Phase 2 Trial in De Novo Oligometastatic Prostate Cancer. Eur Urol 2024;86:190–3. https://doi.org/10.1016/j.eururo.2024.02.008. Reverberi C, Massaro M, Osti MF, Anzellini D, Marinelli L, Montalto A, et al. Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer. Sci Rep 2020;10:17471. https://doi.org/10.1038/s41598-020-74562-3. Warner EW, Van Der Eecken K, Murtha AJ, Kwan EM, Herberts C, Sipola J, et al. Multiregion sampling of de novo metastatic prostate cancer reveals complex polyclonality and augments clinical genotyping. Nat Cancer 2024;5:114–30. https://doi.org/10.1038/s43018-023-00692-y. Additional Declarations There is NO conflict of interest to disclose. Cite Share Download PDF Status: Published Journal Publication published 11 Dec, 2025 Read the published version in Prostate Cancer and Prostatic Diseases → Version 1 posted Editorial decision: revise 03 Jul, 2025 Review # 3 received at journal 12 Jun, 2025 Reviewer # 3 agreed at journal 31 May, 2025 Reviewer # 2 agreed at journal 30 May, 2025 Review # 1 received at journal 30 May, 2025 Reviewer # 1 agreed at journal 30 May, 2025 Reviewers invited by journal 28 May, 2025 Editor assigned by journal 28 May, 2025 Submission checks completed at journal 27 May, 2025 First submitted to journal 24 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6740073","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":463028109,"identity":"242afbb7-db80-4426-a555-84f832af5a9b","order_by":0,"name":"Vedang Murthy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYHACAyjNw8DwAUixsROthY2HgXEGiGYmRQszD4hBSIvB8eaNnwt+bUvcPr/3mLTNr23yfMwMjB8+5uDRcuZYsfTMvtuJc47xpUnn9t02bGNmYJacuQ23FskZOQbSvD23E2ew8ZhJ5/bcZgRqYWPmxadl/hvj33Atlj237Qlq4ZcAquT5AdXCAGQQ1sKTVmbN23DbeAZbjrFlb8Pt5DZmxma8fmFjP7z5Ns+f27IzmM8Y3vjx57bt/Pbmgx8+4tECBoxtYIpFAsJgbCCgHgT+gEnmD1DGKBgFo2AUjAIUAABcCk3SbBaw9gAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-6011-9319","institution":"TATA Memorial Hospital","correspondingAuthor":true,"prefix":"","firstName":"Vedang","middleName":"","lastName":"Murthy","suffix":""},{"id":463028110,"identity":"4bf6aaef-6f2f-4c86-9919-16e6941b9d38","order_by":1,"name":"Parth Verma","email":"","orcid":"","institution":"TATA Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Parth","middleName":"","lastName":"Verma","suffix":""},{"id":463028111,"identity":"82a00839-3246-494f-b2b7-e8a5fd80be66","order_by":2,"name":"Priyamvada Maitre","email":"","orcid":"https://orcid.org/0000-0002-8878-7914","institution":"Tata Memorial Centre","correspondingAuthor":false,"prefix":"","firstName":"Priyamvada","middleName":"","lastName":"Maitre","suffix":""},{"id":463028112,"identity":"1e73bfe6-8663-46d4-9509-5f370a35b6fe","order_by":3,"name":"Gowtham Surya Krishnasamy","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Gowtham","middleName":"Surya","lastName":"Krishnasamy","suffix":""},{"id":463028113,"identity":"d6dce7ca-7ea0-4c4e-94b2-6d2d51fe62f5","order_by":4,"name":"Nishika Murarka","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Nishika","middleName":"","lastName":"Murarka","suffix":""},{"id":463028114,"identity":"62cdf7a4-9db9-4380-9b09-4c83ae0dc793","order_by":5,"name":"Sayak Choudhury","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Sayak","middleName":"","lastName":"Choudhury","suffix":""},{"id":463028115,"identity":"4ff2f75a-b66d-47c9-a21f-64f34d5e0e4b","order_by":6,"name":"Suchismita Ghosh","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Suchismita","middleName":"","lastName":"Ghosh","suffix":""},{"id":463028116,"identity":"95ff2da2-7abe-472a-8de2-5fc0747eb5b2","order_by":7,"name":"Archi Agarwal","email":"","orcid":"","institution":"Tata Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Archi","middleName":"","lastName":"Agarwal","suffix":""}],"badges":[],"createdAt":"2025-05-24 16:20:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6740073/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6740073/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41391-025-01056-6","type":"published","date":"2025-12-11T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83772700,"identity":"13d444aa-64e5-410a-a382-55097d1fe0e1","added_by":"auto","created_at":"2025-06-02 12:57:36","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":25695,"visible":true,"origin":"","legend":"\u003cp\u003ePatterns of progression (n=15). Of the 15 patients who progressed, 4 patients (26.7%) had progression limited to the index metastatic site only, while 7 (46.6%) showed progression in the index site with new metastatic lesions. Four patients (26.7%) had progression in new metastatic lesions only.\u003c/p\u003e","description":"","filename":"Slide1.png","url":"https://assets-eu.researchsquare.com/files/rs-6740073/v1/4db36ba4558be1a843160437.png"},{"id":97957239,"identity":"9a53deac-fe6e-47ce-ac58-58ed5f19499c","added_by":"auto","created_at":"2025-12-11 08:12:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":474397,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6740073/v1/dcaf3396-2150-40a0-bede-35c1759cd65d.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Progression of Index Metastases in Oligometastatic Hormone-Sensitive Prostate Cancer: Implications for Metastasis-Directed Therapy?","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eDe novo oligometastatic hormone sensitive prostate cancer (omHSPC) is typically treated with a combination of lifelong androgen deprivation therapy (ADT), androgen receptor pathway inhibitors (ARPI), and radiotherapy to the prostate. The role of metastasis-directed therapy (MDT) is not established yet. The Advanced Prostate Cancer Consensus Conference (APCCC) 2024 expert panel did not reach consensus on utilisation of MDT for de-novo omHSPC, with only 17% experts favouring MDT based on conventional imaging and 57% voting for additional next-generation imaging before deciding about MDT [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Prostate specific membrane antigen (PSMA) based imaging (such as PSMA-PET/CT) is now preferred for more accurate disease staging and localisation of smaller metastases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Currently MDT is not recommended by most global guidelines, and its utilisation is discretionary [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eKey trials in omHSPC such as STAMPEDE and PEACE-1 have reported on the benefit of prostate radiotherapy in omHSPC, staged with conventional imaging [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Details of the patterns of progression are not known, which would help understand the potential role of MDT for the index oligometastases. Therefore, we explored the institutional cohort of PSMA-staged de novo omHSPC treated with ADT and prostate radiotherapy, for sites of disease progression in consideration of the index metastatic lesions.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e This IRB approved study queried a prospectively maintained database at a large tertiary cancer care centre. We included patients diagnosed with de novo omHSPC, staged with PSMA-PET/CT at diagnosis, and fulfilling the CHAARTED criteria - disease in non-regional lymph nodes or \u0026lt;\u0026thinsp;5 bone metastases, in the absence of visceral metastases [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. All patients were treated with standard of care systemic therapy and radiotherapy to the prostate, without MDT. Follow up was based on PSA, and at biochemical progression all patients underwent a restaging PSMA-PET/CT. Patients with high volume disease, those with castration resistant disease prior to radiotherapy, or those with diagnostic or restaging scan unavailable, were excluded. The individual sites of disease recurrence in the restaging scans were mapped with respect to the index site of metastases in the index scan by nuclear medicine physicians experienced in reporting PSMA-PET/CT. Known prognostic factors - Gleason grade group (4\u0026ndash;5 vs 1\u0026ndash;3), nodal involvement (N1 vs N0), bone metastases (M1b vs M1a), systemic intensification (intensified ADT vs ADT alone), 6-month nadir PSA (\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026le;\u003c/span\u003e\u0026thinsp;0.1 ng/mL vs higher) - were evaluated for risk of progression of the index metastasis by calculating odds ratio. A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. Data was analysed using IBM SPSS v21.0.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 79 eligible patients treated from January 2015 to January 2024 were included (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Majority (82%) had Gleason grade group 4 or 5 disease. Bony metastases were present in 72% of patients. About 75% received ADT intensified with either ARPI or docetaxel. At a median follow up of 39 months (IQR 28\u0026ndash;69), 19% patients (n\u0026thinsp;=\u0026thinsp;15) had progression. Median time to progression was 28 months (IQR 24\u0026ndash;37) from the start of ADT. Restaging PSMA-PET/CT showed visible progression at the index metastases in 11/15 (73.3%) patients. Four patients (26.7%) had progression limited to the index metastatic site only, while 7 (46.6%) showed progression in the index site with new metastatic lesions [Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e]. None of the prognostic factors showed statistically significant association with progression of index metastases [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient demographics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian PSA (ng/ml, IQR)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.8 (15.4\u0026ndash;79.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGleasons group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e3\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e4\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e5\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNot known\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ecT Stage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eT2\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eT3a\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eT3b\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eT4a\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUnknown\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ecN Stage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eN0\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eN1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ecM Stage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eM1a\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eM1b\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHormonal Therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eADT\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (25.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eADT\u0026thinsp;+\u0026thinsp;ARPI\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (59.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eADT\u0026thinsp;+\u0026thinsp;Docetaxel\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (13.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eADT\u0026thinsp;+\u0026thinsp;ARPI\u0026thinsp;+\u0026thinsp;Docetaxel\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analysis for known prognostic factors versus progression of index metastases.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecN0 vs cN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.7 (0.1\u0026ndash;22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM1a vs M1b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.6 (0.3\u0026ndash;46.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGS 1\u0026ndash;3 vs 4\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.3 (0.01\u0026ndash;6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eADT alone vs intensification\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.7 (0.1\u0026ndash;22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6m PSA\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026le;\u003c/span\u003e\u0026thinsp;0.1 vs\u0026thinsp;\u0026gt;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.1 (0.08\u0026ndash;15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6m PSA\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026le;\u003c/span\u003e\u0026thinsp;0.2 vs\u0026thinsp;\u0026gt;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.8 (0.08\u0026ndash;8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eTo our knowledge, this is the first study to report patterns of recurrence for PSMA-staged omHSPC treated with ADT and prostate radiotherapy without MDT. At progression, restaging PSMA-PET/CT showed progression of index metastases in 75% of the patients, with about a quarter of the patients having progression only at the index site. This suggests a potentially important role of MDT for local control at the site of index oligometastases.\u003c/p\u003e \u003cp\u003eAlthough without robust evidence, the argument in favour of adding MDT to prostate radiotherapy in omHSPC can be threefold. First, very high control rates exceeding 90% have been demonstrated with ablative radiotherapy for metastases, with minimal added toxicities [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Next line systemic therapy was reported to be safely deferred by using MDT in these non-randomised studies, though PSMA-based imaging was not used. Secondly, there might be a clinical advantage of treating the metastases in the de-novo omHSPC setting rather than metachronous setting, supporting total ablation of visible de novo oligometastases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Finally, ablation of index lesions in addition to prostate radiotherapy may disrupt polyclonal seeding of further metastases [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Overall, the potential benefit of MDT would likely depend on reliably mapping the oligometastases with PSMA-based imaging, as well as effective ablation of putative hormone-resistant disease in these lesions.\u003c/p\u003e \u003cp\u003eAcknowledging the inherent limitations of a small cohort from a single centre, our results are strengthened by PSMA-based staging at diagnosis and recurrence, formal review of all scans by experienced nuclear medicine physicians, and a prospectively maintained database. While the value of MDT is under evaluation by the phase III STAMPEDE-2 randomised trial, this study provides an interesting insight into progression of de novo omHSPC after systemic therapy and prostate only radiotherapy. The high proportion of progression at the index site of metastases (75%), without additional metastases in a third of these, suggests a potential role of ablation of oligometastases to optimize overall disease control.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS APPROVAL:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe confirm that all methods were performed in accordance with the relevant guidelines and regulations. Ethical approval was taken from the Institutional Ethical Committee of Tata Memorial Hospital, Mumbai. No informed consent was taken as Ethics Committee granted wavier.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVM conceptualized the study. VM, PM, PV, GSK and NM were involved in patient accrual, data acquisition and study procedures. SC, SG and AA provided technical and material support. PV and PM did statistical analysis. The manuscript was drafted by PV, VM, and PM. All authors approved the final manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGillessen S, Turco F, Davis ID, Efstathiou JA, Fizazi K, James ND, et al. Management of Patients with Advanced Prostate Cancer. Report from the 2024 Advanced Prostate Cancer Consensus Conference (APCCC). Eur Urol 2025;87:157\u0026ndash;216. https://doi.org/10.1016/j.eururo.2024.09.017.\u003c/li\u003e\n\u003cli\u003eHofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. The Lancet 2020;395:1208\u0026ndash;16. https://doi.org/10.1016/S0140-6736(20)30314-7.\u003c/li\u003e\n\u003cli\u003eParker CC, James ND, Brawley CD, Clarke NW, Ali A, Amos CL, et al. Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial. PLoS Med 2022;19:e1003998. https://doi.org/10.1371/journal.pmed.1003998.\u003c/li\u003e\n\u003cli\u003eBossi A, Foulon S, Maldonado X, Sargos P, MacDermott R, Kelly P, et al. Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 \u0026times; 2 factorial design. The Lancet 2024;404:2065\u0026ndash;76. https://doi.org/10.1016/S0140-6736(24)01865-8.\u003c/li\u003e\n\u003cli\u003eKyriakopoulos CE, Chen Y-H, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J Clin Oncol 2018;36:1080\u0026ndash;7. https://doi.org/10.1200/JCO.2017.75.3657.\u003c/li\u003e\n\u003cli\u003eDeodato F, Pezzulla D, Cilla S, Ferro M, Romano C, Bonome P, et al. Stereotactic radiosurgery for bone metastases in oligometastatic prostate cancer patients: DESTROY-2 clinical trial subanalysis. Clin Transl Oncol 2022;24:1177\u0026ndash;83. https://doi.org/10.1007/s12094-021-02764-w.\u003c/li\u003e\n\u003cli\u003eQi X, Li HZ, Gao XS. Radiotherapy of the Primary Tumor and All Metastatic Lesions in Oligometastatic Prostate Cancer: 5-Year Results of Prolong Study. Int J Radiat Oncol 2024;120:S147. https://doi.org/10.1016/j.ijrobp.2024.07.2156.\u003c/li\u003e\n\u003cli\u003eNickols NG, Tsai S, Kane N, Tran S, Ghayouri L, Diaz-Perez S, et al. Systemic and Tumor-directed Therapy for Oligometastatic Prostate Cancer: The SOLAR Phase 2 Trial in De Novo Oligometastatic Prostate Cancer. Eur Urol 2024;86:190\u0026ndash;3. https://doi.org/10.1016/j.eururo.2024.02.008.\u003c/li\u003e\n\u003cli\u003eReverberi C, Massaro M, Osti MF, Anzellini D, Marinelli L, Montalto A, et al. Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer. Sci Rep 2020;10:17471. https://doi.org/10.1038/s41598-020-74562-3.\u003c/li\u003e\n\u003cli\u003eWarner EW, Van Der Eecken K, Murtha AJ, Kwan EM, Herberts C, Sipola J, et al. Multiregion sampling of de novo metastatic prostate cancer reveals complex polyclonality and augments clinical genotyping. Nat Cancer 2024;5:114\u0026ndash;30. https://doi.org/10.1038/s43018-023-00692-y.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"prostate-cancer-and-prostatic-diseases","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"pcan","sideBox":"Learn more about [Prostate Cancer and Prostatic Diseases](http://www.nature.com/pcan/)","snPcode":"41391","submissionUrl":"https://mts-pcan.nature.com/cgi-bin/main.plex","title":"Prostate Cancer and Prostatic Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6740073/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6740073/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003cbr\u003e\n \u003c/strong\u003eFor de-novo oligometastatic prostate cancer (omHSPC) treated with standard of care androgen suppression and prostate radiotherapy, the patterns of progression vis-a-vis index metastatic sites are not well understood.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003cbr\u003e\n \u003c/strong\u003eThis single centre study included patients with de-novo omHSPC (CHAARTED criteria) staged with a PSMA-PET/CT scan at diagnosis, treated with androgen suppression and prostate radiotherapy, and re-staged with PSMA-PET/CT at biochemical progression. Disease status at index oligometastases was noted at progression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003cbr\u003e\n \u003c/strong\u003eFrom 2015 to 2024, 79 patients with omHSPC were found eligible (M1a = 22, M1b = 57). Over a median follow-up of 39 months (IQR 28-69), 15 patients (19%) had disease progression. Restaging PSMA-PET/CT revealed progression of the index oligometastases for 11/15 patients (73%), with additional metastases in 7 of these.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003cbr\u003e\n \u003c/strong\u003eThe high proportion of progression at the index oligometastases supports the potential benefit of metastasis-directed therapy for local ablation.\u003c/p\u003e","manuscriptTitle":"Progression of Index Metastases in Oligometastatic Hormone-Sensitive Prostate Cancer: Implications for Metastasis-Directed Therapy?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-02 12:57:32","doi":"10.21203/rs.3.rs-6740073/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-07-03T12:02:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-12T20:04:41+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-31T07:30:24+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-30T18:07:41+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-05-30T15:04:24+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-30T14:19:41+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-05-28T10:36:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-28T10:19:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-27T14:03:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Prostate Cancer and Prostatic Diseases","date":"2025-05-24T16:16:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"prostate-cancer-and-prostatic-diseases","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"pcan","sideBox":"Learn more about [Prostate Cancer and Prostatic Diseases](http://www.nature.com/pcan/)","snPcode":"41391","submissionUrl":"https://mts-pcan.nature.com/cgi-bin/main.plex","title":"Prostate Cancer and Prostatic Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"57726f87-559a-46ca-a921-1852a66f0461","owner":[],"postedDate":"June 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":49165568,"name":"Biological sciences/Cancer/Urological cancer/Prostate cancer"},{"id":49165569,"name":"Health sciences/Diseases/Cancer/Cancer therapy"}],"tags":[],"updatedAt":"2025-12-11T08:12:38+00:00","versionOfRecord":{"articleIdentity":"rs-6740073","link":"https://doi.org/10.1038/s41391-025-01056-6","journal":{"identity":"prostate-cancer-and-prostatic-diseases","isVorOnly":false,"title":"Prostate Cancer and Prostatic Diseases"},"publishedOn":"2025-12-11 05:00:00","publishedOnDateReadable":"December 11th, 2025"},"versionCreatedAt":"2025-06-02 12:57:32","video":"","vorDoi":"10.1038/s41391-025-01056-6","vorDoiUrl":"https://doi.org/10.1038/s41391-025-01056-6","workflowStages":[]},"version":"v1","identity":"rs-6740073","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6740073","identity":"rs-6740073","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}