Stereotactic Focal Radiotherapy as an Alternative Treatment to Active Surveillance for Low and Intermediate Risk Prostate Cancer

\*Rationale : Active surveillance of prostate cancer helps to avoid the morbidity associated with curative radical prostatectomy /radiotherapy in patients with early stage disease. However, at 5 years and 15 years, respectively 35 % and nearly 50 % of patients require rescue interventional treatments. Numerous Phase II trials have reported using focal treatments (focused on the macroscopic tumor only while not involving the whole prostatic gland) in order to reduce the morbidity due to recurrence as well as the high anxiety rates under observation only. Stereotactic radiotherapy (highly focused radiotherapy technic to reduce the risk of side effects) is being proposed in the same way as it does not require any anaesthesia, as opposed to all the other focal methods. The purpose of this trial is to evaluate whether focal stereotactic radiotherapy treatments could reduce the rate of rescue treatments among patients eligible to an active surveillance program at first. * Major Inclusion Criteria : * 1\. Early stage prostate adenocarcinoma (CAPRA score ≤ 5) * 2\. No major urinary problems * 3\. Active Surveillance possible * Major Exclusion Criteria : * 1\. Age at diagnosis \< 50 years * 8\. Androgen-deprivation therapy * 9\. Any cancer within the last 5 years except skin basocellular carcinoma or any uncontrolled cancer * Trial : Phase II randomized trial comparing Stereotactic Radiation Therapy focused on the macroscopic tumor or Active Surveillance as the control arm. * Main objective : to compare the rescue treatment rates between the two arms

Sex

Male

Minimum age

50 Years

* Inclusion Criteria (all the criteria must be fulfilled ) :

  * a. Localized prostate adenocarcinoma CAPRA score ≤ 5. This lesion is considered the Index lesion
  * b. Macroscopic tumor PIRADS score \>4 on multiparametric MRI
  * c. The biopsies must be pathologic in or in the direct vicinity (the same prostatic zone defined as a quarter volume of the prostate (PZ)) of the MRI pathologic nodule
  * d. The absence of MRI pathologic criteria (PIRADS ≤3) in a Gleason score ≤ 6 (3+3)-ISUP Grade1 zone outside of the single Index lesion is considered clinically non-significant and does not preclude inclusion
  * e. The lesion can be plurifocal in a same intent to treat PZ
  * f. WHO Performance Status 0-1
  * g. No major urinary symptoms with IPSS score ≤15 and urinary continence ICIQ score =0
  * h. Patient is candidate for AS
* Exclusion Criteria :

  * a. Age at diagnosis \< 50 years
  * b. Time between initial diagnostic biopsies and randomization \> 4 months, or radiation therapy initiation \> 6 months
  * c. Cribriform or Intraductal histologic components
  * d. Gleason Score ≥7 (3+4)-ISUP Grade 2 biopsy outside the intent to treat PZ
  * e. Multicentric pathologic MRI (PIRADS ≥4) outside a same PZ
  * f. Initial PSA \> 20 ng/ml
  * g. Regional pathologic nodes or metastases
  * h. Androgen-deprivation therapy
  * i. Any cancer within the last 5 years except skin basocellular carcinoma or any uncontrolled cancer
  * j. Urethral stenosis
  * k. Recurrent prostatitis (at least 3 episodes within the last 3 years)
  * l. Any inflammatory collagen disease.
  * m. Contraindication to repeated prostatic biopsies or MRI

• BACKGROUNDNguyen PV, Donneaux B, Louis C, Bodgal Z, Philippi S, Biver S, Frederick B, Harze L, Lasar Y, Vogin G, Nickers P. Stereotactic focal radiotherapy as an alternative treatment for low-risk prostate cancer: Results of a single-arm monocenter Phase-II trial. Front Oncol. 2023 Apr 6;13:1143716. doi: 10.3389/fonc.2023.1143716. eCollection 2023. PMID 37091187
• BACKGROUNDNewcomb LF, Schenk JM, Zheng Y, Liu M, Zhu K, Brooks JD, Carroll PR, Dash A, de la Calle CM, Ellis WJ, Filson CP, Gleave ME, Liss MA, Martin F, McKenney JK, Morgan TM, Tretiakova MS, Wagner AA, Nelson PS, Lin DW. Long-Term Outcomes in Patients Using Protocol-Directed Active Surveillance for Prostate Cancer. JAMA. 2024 Jun 25;331(24):2084-2093. doi: 10.1001/jama.2024.6695. PMID 38814624
• BACKGROUNDHopstaken JS, Bomers JGR, Sedelaar MJP, Valerio M, Futterer JJ, Rovers MM. An Updated Systematic Review on Focal Therapy in Localized Prostate Cancer: What Has Changed over the Past 5 Years? Eur Urol. 2022 Jan;81(1):5-33. doi: 10.1016/j.eururo.2021.08.005. Epub 2021 Sep 4. PMID 34489140
• BACKGROUNDHamdy FC, Donovan JL, Lane JA, Metcalfe C, Davis M, Turner EL, Martin RM, Young GJ, Walsh EI, Bryant RJ, Bollina P, Doble A, Doherty A, Gillatt D, Gnanapragasam V, Hughes O, Kockelbergh R, Kynaston H, Paul A, Paez E, Powell P, Rosario DJ, Rowe E, Mason M, Catto JWF, Peters TJ, Oxley J, Williams NJ, Staffurth J, Neal DE; ProtecT Study Group. Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2023 Apr 27;388(17):1547-1558. doi: 10.1056/NEJMoa2214122. Epub 2023 Mar 11. PMID 36912538