Outcomes of combined radiotherapy in high-risk prostate cancer

Radiotherapy is one of the radical treatment options used in patients with prostate cancer (PC). Many studies of combined radiotherapy (CRT) for PC have demonstrated good results in respect of response to treatment; however, the sequence of CRT steps and optimal interval between them have not been determined so far. Few randomized studies have been conducted in order to confirm the advantages of brachytherapy at the first or second step or determine the most effective interval between the contact and external beam RT. Therefore, it appears reasonable to evaluate different CRT techniques.

Purpose. The goal of the study was to evaluate the outcomes of PC treatment depending on the sequence of CRT steps and the interval between them.

Materials and methods. 53 patients with PC received ¹²⁵I radiation therapy in combination with long-term hormone therapy (HT). Median follow-up was 38 months. Patients’ age varied from 54 to 81 years. All patients were in a high-risk group according to the D’Amico Risk Classification System. The patients were allocated to two groups: in Group 1, brachytherapy was used as the first step (n=31); in Group 2, it was applied after external beam therapy (EBT). The interval between the CRT steps could be less than 4 weeks (n=6), 4 – 7 weeks (n=17) and more than 8 weeks (n=30). Standard fractionation EBT with a total dose of 46 Gy using the VMAT technique was conducted. ¹²⁵I prostate implants were inserted to reach a total dose of 110 Gy. Neoadjuvant (2 – 4 months) and adjuvant (not less than 24 months) regimens of HT were applied.

Results. Five (9.4 %) patients had disease progression; two of them experienced only biochemical recurrence; distant metastases were diagnosed in three patients. Median time to disease progression was 29.9 months. One patient with a biochemical relapse died of acute myocardial infarction (1.9 %). Median five-year disease-free survival was 84.5±11.7 % in Group 1 and 83.5±9.1 (p=0.73) in Group 2. There were no significant differences in the incidence of toxicity depending on the sequence of CRT steps.

Conclusion. EBT using ¹²⁵I radiation sources in combination with long-term hormone therapy is an effective and safe treatment option for high-risk PC patients. No significant increase in the incidence of disease progression was observed when the interval between the CRT steps was increased to more than 8 weeks. Changes in the sequence of CRT steps do not affect response to treatment or incidence of radiation-related complications.

1. Под ред. А. Д. Каприна, В. В. Старинского, Г. В. Петровой Злокачественные новообразования в России в 2018 году (заболеваемость и смертность) М.: МНИОИ им. П. А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2019. илл. 250 с. ISBN 978‑5‑85502‑243‑8

2. Hanks GE, Martz KL, Diamond JJ. The effect of dose on local control of prostate cancer. // Int J Radiat Oncol Biol Phys. 1988 Dec; 15 (6):1299 – 305.

3. Zelefsky MJ, Pei X, Chou JF, Schechter M, Kollmeier M, Cox B, Yamada Y, Fidaleo A, Sperling D, Happersett L, Zhang Z. Dose escalation for prostate cancer radiotherapy: predictors of long-term biochemical tumor control and distant metastases-free survival outcomes. Eur Urol. 2011 Dec;60 (6):1133 – 9. doi: 10.1016 / j. eururo. 2011.08.029. Epub 2011 Aug 22. PMID: 21889832; PMCID: PMC4037155.

4. Zelefsky MJ, Fuks Z, Wolfe T et al. Locally advanced prostatic cancer: long-term toxicity outcome after three-dimensional conformal radiation therapy: a dose-escalation study. // Radiology. 1998 Oct; 209 (1):169 – 74.

5. International Commission on Radiation Units and Measurements. Prescribing, Recording, and Reporting Photon Beam Therapy (Supplement to ICRU Report 50). ICRU Report 62. Bethesda, MD: International Commission on Radiation Units and Measurements, 1999

6. Roach, M., Hanks, G., Thames, H., Schellhammer, P., Shipley, W. U., Sokol, G. H., & Sandler, H. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: Recommendations of the RTOG-ASTRO Phoenix Consensus Conference. International Journal of Radiation Oncology Biol. Phys., 65 (4), 965 – 974. doi:10.1016 / j. ijrobp. 2006.04.029

7. Sylvester JE, Grimm PD, Blasko JC, et al: 15‑year biochemical relapse free survival in clinical stage T1‑T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience. Int J Radiat Oncol Biol Phys 67:57 – 64, 2007

8. Critz FA, Levinson K: 10‑year disease-free survival rates after simultaneous irradiation for prostate cancer with a focus on calculation methodology. J Urol 172:2232 – 2238, 2004

9. Morris WJ, Tyldesley S, Rodda S, Halperin R, Pai H, McKenzie M, Duncan G, Morton G, Hamm J, Murray N, *ASCENDE-RT: An Analysis of Survial Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- And Intermediate-Risk Prostate Cancer, International Journal of Radiation Oncology • Biology • Physics (2016), doi: 10.1016 / j. ijrobp. 2016.11.026.

10. Lawton CA, Yan Y, Lee WR, et al. Long-term results of an RTOG phase II trial (00-19) of external-beam radiation therapy combined with permanent source brachytherapy for intermediate-risk clinically localized adenocarcinoma of the prostate. Int J Radiat Oncol Biol Phys 2012;82: e795ee801.

11. Spratt, D. E., Zumsteg, Z. S., Ghadjar, P., Kollmeier, M. A., Pei, X., Cohen, G., Zelefsky, M. J. (2014). Comparison of highdose (86.4 Gy) IMRT vs combined brachytherapy plus IMRT for intermediate-risk prostate cancer. BJU International, 360 – 367. doi:10.1111 / bju. 12514

12. Shilkrut M, Merrick GS, McLaughlin PW, et al. The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer. Cancer 2013; 119:681e690.