Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience
Abstract Background Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it’s use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. H...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | Radiation Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13014-021-01808-3 |
| _version_ | 1829518470418530304 |
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| author | Jure Murgic Blanka Jaksic Marin Prpic Davor Kust Amit Bahl Mirjana Budanec Angela Prgomet Secan Pierfrancesco Franco Ivan Kruljac Borislav Spajic Nenad Babic Bozo Kruslin Mario Zovak Eduardo Zubizarreta Eduardo Rosenblatt Ana Fröbe |
| author_facet | Jure Murgic Blanka Jaksic Marin Prpic Davor Kust Amit Bahl Mirjana Budanec Angela Prgomet Secan Pierfrancesco Franco Ivan Kruljac Borislav Spajic Nenad Babic Bozo Kruslin Mario Zovak Eduardo Zubizarreta Eduardo Rosenblatt Ana Fröbe |
| author_sort | Jure Murgic |
| collection | DOAJ |
| description | Abstract Background Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it’s use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. Methods Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan–Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Results Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58–106 months, range, 8–106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41–72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0–4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0–4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0–1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2–8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37–6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6–12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03–1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26–9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96–25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03–7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00–1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08–16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. Conclusions In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations. |
| first_indexed | 2024-12-16T14:22:32Z |
| format | Article |
| id | doaj.art-67606cfcee2e4fcaa34a206e64a05416 |
| institution | Directory Open Access Journal |
| issn | 1748-717X |
| language | English |
| last_indexed | 2024-12-16T14:22:32Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Radiation Oncology |
| spelling | doaj.art-67606cfcee2e4fcaa34a206e64a054162022-12-21T22:28:28ZengBMCRadiation Oncology1748-717X2021-05-0116111210.1186/s13014-021-01808-3Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experienceJure Murgic0Blanka Jaksic1Marin Prpic2Davor Kust3Amit Bahl4Mirjana Budanec5Angela Prgomet Secan6Pierfrancesco Franco7Ivan Kruljac8Borislav Spajic9Nenad Babic10Bozo Kruslin11Mario Zovak12Eduardo Zubizarreta13Eduardo Rosenblatt14Ana Fröbe15Department of Oncology and Nuclear Medicine, University Hospital Center Sestre MilosrdniceDepartment of Oncology and Nuclear Medicine, University Hospital Center Sestre MilosrdniceDepartment of Oncology and Nuclear Medicine, University Hospital Center Sestre MilosrdniceDepartment of Oncology and Nuclear Medicine, University Hospital Center Sestre MilosrdniceUniversity Hospitals Bristol NHS Foundation TrustDepartment of Oncology and Nuclear Medicine, University Hospital Center Sestre MilosrdniceDepartment of Oncology and Nuclear Medicine, University Hospital Center Sestre MilosrdniceDepartment of Translational Medicine, University of Eastern PiedmontDepartment of Endocrinology, Diabetes and Metabolic Diseases “Mladen Sekso”, University Hospital Center Sestre Milosrdnice, University of Zagreb School of MedicineDepartment of Urology, University Hospital Center Sestre MilosrdniceDepartment of Radiology, University Hospital Center Sestre MilosrdniceLjudevit Jurak Department of Pathology and Cytology, Sestre Milosrdnice University Hospital CentreDepartment of Surgery, University Hospital Center Sestre MilosrdniceDivision of Human Health, International Atomic Energy Agency (IAEA)Division of Human Health, International Atomic Energy Agency (IAEA)Department of Oncology and Nuclear Medicine, University Hospital Center Sestre MilosrdniceAbstract Background Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it’s use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. Methods Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan–Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Results Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58–106 months, range, 8–106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41–72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0–4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0–4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0–1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2–8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37–6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6–12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03–1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26–9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96–25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03–7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00–1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08–16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. Conclusions In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.https://doi.org/10.1186/s13014-021-01808-3Radical prostatectomyProstate cancerSalvage radiotherapyHypofractionationStandard fractionationProstate-specific antigen persistence |
| spellingShingle | Jure Murgic Blanka Jaksic Marin Prpic Davor Kust Amit Bahl Mirjana Budanec Angela Prgomet Secan Pierfrancesco Franco Ivan Kruljac Borislav Spajic Nenad Babic Bozo Kruslin Mario Zovak Eduardo Zubizarreta Eduardo Rosenblatt Ana Fröbe Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience Radiation Oncology Radical prostatectomy Prostate cancer Salvage radiotherapy Hypofractionation Standard fractionation Prostate-specific antigen persistence |
| title | Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience |
| title_full | Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience |
| title_fullStr | Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience |
| title_full_unstemmed | Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience |
| title_short | Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience |
| title_sort | comparison of hypofractionation and standard fractionation for post prostatectomy salvage radiotherapy in patients with persistent psa single institution experience |
| topic | Radical prostatectomy Prostate cancer Salvage radiotherapy Hypofractionation Standard fractionation Prostate-specific antigen persistence |
| url | https://doi.org/10.1186/s13014-021-01808-3 |
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