Intensified adjuvant treatment of prostate carcinoma: Feasibility analysis of a phase I/II trial - Beyond the Abstract

Although adjuvant radiotherapy (RT) after radical prostatectomy (RP) in high-risk patients is recommended by international guidelines, its usage is still matter of debate. (1, 2)

Three recent randomized trials confirmed better biochemical disease-free survival (BDFS) when adjuvant RT was administered (3-5), as already observed in the EORTC-22911 previously (6) Anyway, in these trials a rate of biochemical failure rate was between 25% and 35% in the adjuvant RT arm, probably related to the irradiation of only prostate bed, to low total dose (60 Gy in most patients) and also to a different definitions of biochemical relapse.

The delivery of higher dose and elective pelvic lymph nodes irradiation was considered at risk to increase toxicity with the available radiation technology of that time.

We designed a phase I/II trial to test the feasibility of an intensified adjuvant RT treatment, with higher dose on prostate bed in patients with positive resection margins and/or perineural invasion. Moreover, in mostly of high-risk patients, we added pelvic lymph nodes irradiation and adjuvant hormonal therapy (AHT).

With the limitations of a small sample size (123 pts), short follow up (median 50 months) and absence of stratification for AHT, we reported low acute and late toxicities rates similar to other non randomized studies that used similar higher adjuvant RT dose.

New technologies, as Intensity Modulated RT (IMRT) and Image-guided RT (IGRT) seemed effective to keep acute and late toxicity rates low and to favour also the use of other schedules, like Simultaneous Integrated Boost or Hypofractionation, with a lower overall treatment time and similar low acute toxicity rates (7).

To limit the use of adjuvant RT only in patients with actual high risk of recurrence, on going prospective trials are investigating the opportunity of salvage RT, early salvage RT, adjuvant RT and AHT based on the increase of postoperative values of PSA. A recent review of the literature (8) showed that early salvage RT, delivered when post surgery PSA is <0.5 ng/ml improved 5-year BDFS compared with salvage RT in which pre-RT PSA was >0.5 ng/ml.

Adjuvant RT treatment, on the basis of the pre-RP risk factors and especially of the post-RP histological findings, should be discussed in a multidisciplinary team routinely.

Modern technologies seems improving the feasibility and the tolerance of adjuvant RT treatment, supporting its role in high-risk patients.

1. Heidenreich A, Bastian PJ, Bellmunt J et al. EAU guidelines on prostate cancer—part 1: screening, diagnosis, and local treatment with curative intent-update. Eur Urol 2014, 65:124–137, 2014.
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3. Wiegel T, Bottke D, Steiner U et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96- 02/AUO AP 09/95.J Clin Oncol 2009, 27 (18): 2924–2930.
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5. Thompson IM Jr, Tangen CM, Paradelo J et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 2006, 296 (19): 2329–2335.
6. Bolla M, Van Poppel H, Collette L et al. Postoperative radiotherapy after radical prostatectomy: a randomized controlled trial (EORTC trial 22911). Lancet 2005, 366 (9485): 572–578.
7. Katayama S, Thorbjoern S, Kessel K, et al. Hypofractionated IMRT of the prostate bed after radical prostatectomy: acute toxicity in the PRIAMOS-1 Trial. Int J Radiat Oncol Biol Phys 2014, Nov 90(4): 926-33.
8. Pfister D, Bolla M, Briganti A, et al. Early salvage radiotherapy following radical prostatectomy. EurUrol2014, 65: 1034-1043.

Written by:
A.R. Alitto, MD, V. Valentini, MD, and G. Mantini, MD
Radiation Oncology Department, Gemelli-ART, Università Cattolica S.Cuore, Rome.

Intensified adjuvant treatment of prostate carcinoma: Feasibility analysis of a phase I/II trial