Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate-High Risk Prostate Cancer: Insights from a Phase I/II Study

Version 1 : Received: 24 May 2024 / Approved: 24 May 2024 / Online: 24 May 2024 (13:59:34 CEST)

A peer-reviewed article of this Preprint also exists.

Cloître, M.; Benkhaled, S.; Boughdad, S.; Schaefer, N.; Prior, J.O.; Zeverino, M.; Berthold, D.; Tawadros, T.; Meuwly, J.-Y.; Martel, P.; Rohner, C.; Heym, L.; Duclos, F.; Vallet, V.; Valerio, M.; Bourhis, J.; Herrera, F. Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate–High-Risk Prostate Cancer: Insights from a Phase I/II Study. Cancers 2024, 16, 2097. Cloître, M.; Benkhaled, S.; Boughdad, S.; Schaefer, N.; Prior, J.O.; Zeverino, M.; Berthold, D.; Tawadros, T.; Meuwly, J.-Y.; Martel, P.; Rohner, C.; Heym, L.; Duclos, F.; Vallet, V.; Valerio, M.; Bourhis, J.; Herrera, F. Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate–High-Risk Prostate Cancer: Insights from a Phase I/II Study. Cancers 2024, 16, 2097.

Abstract

Simple summary This reassessment of the findings from our Phase I/II study seeks to evaluate the effectiveness of SBRT for treating local intermediate-high risk prostate cancer in the absence of androgen-deprivation therapy due to patient’s refusal, with a median follow-up of 6.5 years. Our primary focus is on analysing the treated areas compared to recurrence patterns in the seven patients who experienced local relapse. Additionally, we provide updated data on late toxicities of grade 2 or higher, both genitourinary and gastrointestinal. Abstract Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intraprostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intraprostatic recurrences occurred in 7 patients (21%), with ≥ 75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patient. Notably, 5 patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intraprostatic recurrences. Extended follow-up revealed grade 2 or higher late GU and GI toxicity in 18% (n=6) and 6% (n=2) of the patients. Conclusions: Among patients with intermediate-high risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: focal dose escalated prostate SBRT prevented recurrences in the dominant nodule, however extra-prostatic recurrence sites were frequent.

Keywords

pattern of recurrence; prostate cancer; intermediate-high risk; SBRT; stereotactic treatment; dosimetry analysis

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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