APCCC 2022: Biochemical Recurrence After Definitive Radiotherapy of the Prostate – What Are the Local Treatment Options?

(UroToday.com) The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on biochemical recurrence, and a presentation by Dr. Jochen Walz discussing local treatment options for biochemical recurrence after definitive radiotherapy. Dr. Walz started his presentation by highlighting the frequency of local recurrence. Local failure rates after radiotherapy are ~17-40% if PSMA PET/CT is used for restaging, and thus we need to think about local salvage therapy options. Staging depends on the intended management, which may include MRI, PSMA PET/CT or biopsy.

In the setting of detection of local recurrence after radiotherapy, MRI has a sensitivity of 82% (95% CI 75-88%) and a specificity of 74% (95% CI 64-82%). PSMA PET/CT is likely to play a very prominent role in the staging of these patients: sensitivity is 35% and specificity is 100% for detecting lymph node involvement in the salvage setting, and sensitivity is 81% and specificity is 67% for intraprostatic recurrence detection. Furthermore, PSMA PET/CT identifies 10.5% of patients with locoregional disease, and 18.4% of patients with regional/distant disease:

 

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With regards to the role of biopsy in the detection of local recurrence after radiotherapy, the EAU guidelines note that “given the morbidity of local salvage options, it is necessary to obtain histological proof of the local recurrence before treating the patient.” The nature of radio recurrent prostate cancer is that it often recurs at the site of the primary lesion, with 60-70% being unifocal, however 30-40% can be multi-focal recurrences. Dr. Walz notes that treatment options for these patients include:

  • Surveillance
  • Hormone therapy (not the focus of this presentation)
  • Focal therapy/ablation
  • Re-irradiation
  • Salvage surgery

 

Dr. Walz notes that surveillance is an option for these patients given that radiorecurrent prostate cancer is a slowly progressing disease. For these patients, it is important to estimate several criteria before salvage surgery, including life expectancy and risk of cancer progression (high ISUP grade, cT category, and short interval to biochemical failure -- <18 months).

 

Focal therapy/ablation typically includes HIFU, cryotherapy, VTPT, IRE, and laser ablation:

 

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 Valle and colleagues [1] performed a systematic review to assess the efficacy and toxicity of salvage radical prostatectomy, high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy. Among 150 studies included in the analysis, adjusted 5-year RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and radical prostatectomy. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with radical prostatectomy (adjusted rates of 20% after RP versus 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with radical prostatectomy (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified:

 

APCCC_2022_Walz_2 

 

 Key outcome predictors for HIFU include (i) selection of unifocal disease, (ii) quantitative DCE parameters (heat sink effect), (iii) PSA level, and (iv) prostate volume. Key outcome predictors for cryoablation include (i) selection of unifocal disease, (ii) PSA <5 ng/mL (>5 ng/mL predictions progression to CRPC), (iii) long-interval between radiotherapy and cryoablation, and (iv) post-cyrotherapy PSA nadir. When considering re-irradiation, clinicians should aim for <131 Gy of combined irradiation, with key predictors for appropriate outcomes including PSA, PSA doubling time, and tumor volume. Outcome prediction after salvage radical prostatectomy includes (i) PSA at the time of surgery, (ii) clinical stage, (iii) number of positive cores before surgery, and (iv) Gleason score.

 

Dr. Walz concluded his presentation by discussing local treatment options after radiotherapy biochemical recurrence with the following take-home messages:

  • Consider local salvage treatment
  • Patient and cancer selection is key for successful salvage treatment
  • For decision making, realistic counseling is essential
  • When salvage treatment is done, it should be done at high volume centers

 


Presented By: Jochen Walz, MD, Institut Paoli-Calmettes Cancer Center, Marseille, France

Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Annual Hybrid Meeting, Lugano, Switzerland, Thurs, Apr 28 – Sat, Apr 30, 2022.


References:
  1. Valle LF, Lehrer EJ, Markovic D, et al. A systematic review and meta-analysis of local salvage therapies after radiotherapy for prostate cancer (MASTER). Eur Urol. 2021 Sep;80(3):280-292.