Ahead of print
Research paper
Published online: 2024-03-09

open access

Page views 163
Article views/downloads 83
Get Citation

Connect on Social Media

Connect on Social Media

Moderate hypofractionated radiotherapy to the prostate bed with or without pelvic lymph nodes: a prospective trial

Juan P. Canales1, Esteban Barnafi2, Cristian Salazar2, Paula Reyes1, Tomás Merino1, David Calderón3, Analía Cortés3

Abstract

Background: Hypofractionated radiotherapy in the treatment of prostate cancer has been widely studied. However, in the postoperative setting it has been less explored. The objective of this prospective study is to evaluate the safety and efficacy of hypofractionated radiotherapy in postoperative prostate cancer.

Materials and methods: A prospective study was designed to include patients with prostate cancer with an indication of postoperative radiotherapy as adjuvant or salvage. A hypofractionated radiotherapy scheme of 51 Gy in 17 fractions was performed with the possibility of treating the pelvis at a dose of 36 Gy in 12 fractions sequentially. Safety was evaluated based on acute and late toxicity [according to the Radiation Therapy Oncology Group (RTOG) scale and Common Terminology Criteria Adverse Events (CTCAE) v4.03], International Prognostic Scoring System (IPSS) over time, and quality of life.

Results: From August 2020 to June 2022, 31 patients completed treatment and were included in this report. 35.5% of patients received elective treatment of the pelvic nodal areas. Most patients reported minimal or low acute toxicity, with an acute gastrointestinal (GI) and genitourinary (GU) grade 3 or greater toxicity of 3.2% and 0%, respectively. The evolution in time of the IPSS remained without significant differences (p = 0.42). With the exception of a significant improvement in the domains of hormonal and sexual symptoms of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire, the rest of the domains [EPIC, European Organization for Research and Treatment of Cancer (EORTC) Core quality of life questionnaire (C-30) and Prostate Cancer module (PR-25)] were maintained without significant differences over time. With a follow-up of 15.4 months, late GI and GU grade 2 toxicity was reported greater than 0% and 9.6%, respectively.

Conclusions: Hypofractionated radiotherapy in postoperative prostate cancer appears to be safe with low reports of relevant acute or late toxicity. Further follow-up is required to confirm these results.

Trial registration: The protocol was approved by the accredited Medical Ethical Committee of Pontificia Universidad Católica de Chile. All participants accepted and wrote informed consent.

 

Article available in PDF format

View PDF Download PDF file

References

  1. Globocan 2018. International Agency for Research on Cancer. World Health Organization .
  2. Han M, Partin AW, Zahurak M, et al. Serum acid phosphatase level and biochemical recurrence following radical prostatectomy for men with clinically localized prostate cancer. Urology. 2001; 57(4): 707–711.
  3. Bolla M, van Poppel H, Tombal B, et al. European Organisation for Research and Treatment of Cancer, Radiation Oncology and Genito-Urinary Groups. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet. 2012; 380(9858): 2018–2027.
  4. Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol. 2009; 181(3): 956–962.
  5. Wiegel T, Bartkowiak D, Bottke D, et al. Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year follow-up of the ARO 96-02/AUO AP 09/95 trial. Eur Urol. 2014; 66(2): 243–250.
  6. Attard G, Murphy L, Clarke NW, et al. STAMPEDE investigators, STAMPEDE collaborators, STAMPEDE Trial Collaborative Group, STAMPEDE Trials Collaborative Group, Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators, STAMPEDE investigators, STAMPEDE investigators, STAMPEDE Investigators, STOPCAP M1 Radiotherapy Collaborators, Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators, STAMPEDE Investigators, STAMPEDE Investigators. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017; 377(4): 338–351.
  7. Sargos P, Chabaud S, Latorzeff I, et al. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020; 21(10): 1341–1352.
  8. Kneebone A, Fraser-Browne C, Duchesne GM, et al. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial. Lancet Oncol. 2020; 21(10): 1331–1340.
  9. Vale CL, Fisher D, Kneebone A, et al. ARTISTIC Meta-analysis Group. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. Lancet. 2020; 396(10260): 1422–1431.
  10. Miralbell R, Roberts SA, Zubizarreta E, et al. Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: Alpha/beta = 1.4 (0.9–2.2) Gy. Int J Radiat Oncol Biol Phys. 2012; 82: e17–e24.
  11. Zemplényi AT, Kaló Z, Kovács G, et al. Cost-effectiveness analysis of intensity-modulated radiation therapy with normal and hypofractionated schemes for the treatment of localised prostate cancer. Eur J Cancer Care (Engl). 2018; 27(1).
  12. Voong KR, Lal LS, Kuban DA, et al. Long-term economic value of hypofractionated prostate radiation: Secondary analysis of a randomized trial. Adv Radiat Oncol. 2017; 2(3): 249–258.
  13. Morgan SC, Hoffman K, Loblaw DA, et al. Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO, and AUA Evidence-Based Guideline. Pract Radiat Oncol. 2018; 8(6): 354–360.
  14. Michalski JM, Lawton C, El Naqa I, et al. Development of RTOG consensus guidelines for the definition of the clinical target volume for postoperative conformal radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2010; 76(2): 361–368.
  15. Lawton CAF, Michalski J, El-Naqa I, et al. RTOG GU Radiation oncology specialists reach consensus on pelvic lymph node volumes for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2009; 74(2): 383–387.
  16. Hall WA, Paulson E, Davis BJ, et al. NRG Oncology Updated International Consensus Atlas on Pelvic Lymph Node Volumes for Intact and Postoperative Prostate Cancer. Int J Radiat Oncol Biol Phys. 2021; 109(1): 174–185.
  17. Gladwish A, Loblaw A, Cheung P, et al. Accelerated hypofractioned postoperative radiotherapy for prostate cancer: a prospective phase I/II study. Clin Oncol (R Coll Radiol). 2015; 27(3): 145–152.
  18. Martell K, Cheung P, Morton G, et al. 5-Year Outcomes of a Prospective Phase 1/2 Study of Accelerated Hypofractionated Radiation Therapy to the Prostate Bed. Pract Radiat Oncol. 2019; 9(5): 354–361.
  19. Picardi C, Perret I, Miralbell R, et al. Hypofractionated radiotherapy for prostate cancer in the postoperative setting: What is the evidence so far? Cancer Treat Rev. 2018; 62: 91–96.
  20. Ippolito E, Cellini N, Digesù C, et al. Postoperative intensity-modulated radiotherapy with simultaneous integrated boost in prostate cancer: a dose-escalation trial. Urol Oncol. 2013; 31(1): 87–92.
  21. Massaccesi M, Cilla S, Deodato F, et al. Hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost after radical prostatectomy: preliminary results of a phase II trial. Anticancer Res. 2013; 33(6): 2785–2789.
  22. Cozzarini C, Fiorino C, Briganti A, et al. Higher-than-expected severe (Grade 3-4) late urinary toxicity after postprostatectomy hypofractionated radiotherapy: a single-institution analysis of 1176 patients. Eur Urol. 2014; 66(6): 1024–1030.
  23. Fersino S, Tebano U, Mazzola R, et al. Moderate Hypofractionated Postprostatectomy Volumetric Modulated Arc Therapy With Daily Image Guidance (VMAT-IGRT): A Mono-institutional Report on Feasibility and Acute Toxicity. Clin Genitourin Cancer. 2017; 15(4): e667–e673.
  24. Macchia G, Siepe G, Capocaccia I, et al. Hypofractionated Postoperative IMRT in Prostate Carcinoma: A Phase I/II Study. Anticancer Res. 2017; 37(10): 5821–5828.
  25. Cuccia F, Mortellaro G, Serretta V, et al. Hypofractionated postoperative helical tomotherapy in prostate cancer: a mono-institutional report of toxicity and clinical outcomes. Cancer Manag Res. 2018; 10: 5053–5060.
  26. Barra S, Belgioia L, Marcenaro M, et al. Moderate hypofractionated radiotherapy after prostatectomy for cancer patients: toxicity and clinical outcome. Cancer Manag Res. 2018; 10: 473–480.
  27. Saldi S, Bellavita R, Lancellotta V, et al. Acute Toxicity Profiles of Hypofractionated Adjuvant and Salvage Radiation Therapy After Radical Prostatectomy: Results of a Prospective Study. Int J Radiat Oncol Biol Phys. 2019; 103(1): 105–111.
  28. Pfister D, Haidl F, Nestler T, et al. Ga-PSMA-PET/CT helps to select patients for salvage radical prostatectomy with local recurrence after primary radiotherapy for prostate cancer. BJU Int. 2020; 126(6): 679–683.
  29. Pisansky TM, Thompson IM, Valicenti RK, et al. Adjuvant and Salvage Radiation Therapy After Prostatectomy: ASTRO/AUA Guideline Amendment, Executive Summary 2018. Pract Radiat Oncol. 2019; 9(4): 208–213.
  30. Leite ET, Ramos CC, Ribeiro VA, et al. Hypofractionated Radiation Therapy to the Prostate Bed With Intensity-Modulated Radiation Therapy (IMRT): A Phase 2 Trial. Int J Radiat Oncol Biol Phys. 2021; 109(5): 1263–1270.
  31. Roach M, DeSilvio M, Lawton C, et al. Radiation Therapy Oncology Group 9413. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol. 2003; 21(10): 1904–1911.
  32. Buyyounouski MK, Pugh S, Chen RC, et al. Primary Endpoint Analysis of a Randomized Phase III Trial of Hypofractionated vs. Conventional Post-Prostatectomy Radiotherapy: NRG Oncology GU003. Int J Radiat Oncol Biol Phys. 2021; 111(3): S2–S3.
  33. Luiting HB, van Leeuwen PJ, Busstra MB, et al. Use of gallium-68 prostate-specific membrane antigen positron-emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical prostatectomy: an overview of the current literature. BJU Int. 2020; 125(2): 206–214.
  34. Staal FHE, Janssen J, Brouwer CL, et al. Phase III randomised controlled trial on PSMA PET/CT guided hypofractionated salvage prostate bed radiotherapy of biochemical failure after radical prostatectomy for prostate cancer (PERYTON-trial): study protocol. BMC Cancer. 2022; 22(1): 416.
  35. Santos M, Chavez-Nogueda J, Galvis JC, et al. Hypofractionation as a solution to radiotherapy access in latin america: expert perspective. Rep Pract Oncol Radiother. 2022; 27(6): 1094–1105.



Reports of Practical Oncology and Radiotherapy