A subclassification of intermediate-risk prostate cancer patients could lead to more precise guidelines and subsequently better clinical outcomes.
We talked to Prof. Dr. Andreas Böhle about his recent paper on the matter.
How should low-dose-rate (LDR) brachytherapy be integrated into the treatment of intermediate-risk (IR) prostate cancer (PCa) patients? That very much depends on the type of intermediate-risk disease, and a subdivision of the group appears mandatory, according to Prof. Dr. Andreas Böhle. We talked to him about his recent publication “LDR-Brachytherapy monotherapy appears unsuited for NCCN unfavorable intermediate-risk prostate cancer patients”. He and his colleagues analyzed treatment outcomes for different radiotherapy regimens in a historical patient cohort.
Prof. Dr. Andreas Böhle
Prof. Dr. Böhle was trained at the university hospitals of Berlin, Bern, and Lübeck. He is one of the resident urologists at the “Urologisches Gesundheitszentrum Bad Schwartau” and a senior physician at the Urological University Hospital Lübeck. He has been treating patients with prostate cancer for decades and has been specialized in urological oncology for over 20 years.
The results clearly show that a subclassification into favorable intermediate-risk (FIR) and unfavorable intermediate-risk (UIR) facilitates treatment planning and the decision whether to use LDR brachytherapy as a monotherapy or in combination with other radiotherapy options. To get the full picture and to talk about possible implications of these findings, we sat down with Prof. Dr. Böhle for an interview.
Eckert & Ziegler: Professor Böhle, thank you so much for your time. In your last publication, you initially validate the division of intermediate-risk (IR) prostate cancer (PCa) into favorable intermediate-risk (FIR) and unfavorable intermediate-risk (UIR) PCa. What was the trigger for validating this subdivision?
Prof. Dr. Andreas Böhle: Actually, a decision of the “Gemeinsamer Bundesausschuss” (GBA) from 2015 finally led to a non-reimbursement situation for intermediate and high-risk prostate cancer patients treated with brachytherapy in our clinical setting.
To put a fact-based argument against this situation, I monitored many international guidelines and compared them to the recent (2021) German Guidelines on Prostate Cancer.
With regard to intermediate-risk carcinoma, already several years ago, international guidelines began to differentiate between favorable intermediate-risk carcinoma (FIR) and unfavorable intermediate-risk carcinoma (UIR). These both sub-entities showed different biological behaviour and post-treatment outcomes.
As we have treated >3000 patients with brachytherapy alone or in combination with EBRT over the last 20 years, I saw the opportunity to retrospectively re-classify the intermediate-risk group into contemporary “favorable” and “unfavorable” subgroups and analyze them with regard to the treatment received.
E&Z: In the following, you have examined the treatment outcomes of two different radiotherapy regimes in both subgroups. Why in particular radiotherapy?
AB: Generally, the results of radiotherapy are by no means worse than the results of surgery. In close cooperation with our radio-oncologic partners, we routinely offer independent information by both teams to patients with localized prostate cancer.
Nota bene, this procedure is required in the German Prostate Cancer Guidelines, but rarely seen in reality.
Patients may then decide well-informed on any therapy offered. Interestingly, around 80% of these patients finally decide for a brachytherapy-based procedure.
E&Z: How did you analyze this patient cohort?
AB: The selection of patients for therapy was based on the risk stratification and guideline recommendations valid at the time, and thus changed repeatedly since 2003. Initially based on the d´Amico system, supplemented by pathohistological features such as lymphatic and perineural invasion, the assessment of risk factors and of the classification into IR and HR PCa transformed. First by the introduction of WHO grade group (GG) system, with GG2 and GG3 emerging from Gleason 7, and later by the National Cancer Center Network (NCCN) subclassification into “favorable IR” (FIR) and “unfavorable IR” (UIR) subgroups.
Retrospectively, this offered the opportunity to re-categorize patients into the contemporary 4-tiered NCCN guidelines system, in which IR disease is subdivided into FIR and UIR categories. Thus, in our analysis, 4 cohorts could be identified, consisting of FIR and UIR patients, treated with either BT monotherapy, or CRT.
Click the following link for an overview of the difference in classifications and recommendations in S3-, EAU- and NCCN-Guidelines.
E&Z: Which two radiotherapy regimes were compared?
AB: We compared brachytherapy monotherapy (BT) with combined-modality radiation (CRT).
Briefly, CRT consisted of EBRT to prostate, seminal vesicles and regional lymphatic area with 60 Gy, followed by a BT boost with a prescription dose of 100 Gy. CRT included androgen deprivation therapy (ADT) for 1 year after radiotherapy. 125I Low-Dose-Rate-Brachytherapy (LDR-BT) was performed with real-time intraoperative planning method, and a prescription dose of 160 Gy.
In this treatment, small radioactive sources (seeds) are placed inside the prostate, which emit a specific low dose of radiation to its surrounding tissue inside the prostate. By placing the seeds homogeneously throughout the organ, the designated dose can destroy the cancerous cells. This therapy can either be used as the only treatment option (monotherapy) or in combination with external beam radiation therapy (combined-modality radiation therapy).
E&Z: What were the results, in brief?
AB: Retrospective analysis of the 4 treatment groups showed, that biochemical recurrence-free survival (BRFS) and metastases-free survival (MFS) did not differ much between BT and CRT in the favorable intermediate-risk (FIR) group. For unfavorable-risk (UIR) patients, however, combined-modality radiation (CRT) revealed significantly better outcomes with regard to BFRS and MFS than brachytherapy monotherapy.
In multivariable analysis, treatment (BT vs. CRT) was the single-associated factor for biochemical recurrence, and for metastases in the UIR group.
E&Z: What conclusions do you draw from this with regard to the current German guidelines?
AB: Subclassification of IR prostate cancer into FIR and UIR subcategories appears mandatory. Unfortunately, even the newest German Guidelines, dated from 2021, still refer to the 3-tiered d`Amico risk classification from 1998 (!), and state that “…an evaluation of the definition of the intermediate-risk group is planned for the next guidelines update…”.
To my opinion, favorable intermediate-risk (FIR) patients should be included into the indication for brachytherapy monotherapy, whereas unfavorable intermediate-risk (UIR) patients, should be candidates for combined-modality radiation therapy (CRT).
E&Z: Apart from the guidelines, what does your data support for clinical practice?
AB: Our data on intermediate-risk prostate cancer patients strongly support subclassification into FIR and UIR categories. Consequently, for UIR patients combined radiation therapy (EBRT with BT-boost) and androgen-deprival therapy appears justified, whereas in FIR patients LDR-BT monotherapy seems appropriate.
In our interdisciplinary team, we have adopted this recommendation since the beginning of 2023.
E&Z: Based on the results, do you continue to use these therapy regimens in your daily clinical practice?
AB: Yes. We have excellent experience with these regimens, concerning both oncological results and side effects.
E&Z: Professor Dr. Böhle, thank you very much for your insights!
If you’re interested to find out more about LDR Brachytherapy in localized prostate cancer, make sure to check out our interview with Dr. Stefan Carl. He presents interesting results of a long-term evaluation of LDR-BT as a treatment option.