Focal therapy failure: A walk on thin ice

Focal Therapy (FT) for prostate cancer is considered as an organ-preserving surgical technique with few side effects. However, there is no extensive evidence-based data for its effectiveness and it is still regarded as an experimental procedure.

The evidence seems insufficient for FT recommendations

Focal Therapy (FT) for prostate cancer is considered by many patients as well as an increasing number of urologists as an organ-preserving surgical technique with few side effects. However, there is no extensive evidence-based data for its effectiveness. FT is currently still regarded as a purely experimental treatment procedure. And what happens if the FT has failed?

The term "focal therapy" (FT) is actually a term encompassing a number of very different therapeutic approaches. All have in common organ preservation so that only the tumor is approached and the surrounding healthy tissue is spared. These include high-intensity focused ultrasound (HIFU), cryotherapy, photodynamic therapy (PDT), vascular targeted photodynamic therapy (VTP) and irreversible electroporation (IRE).

Different approaches, only one goal

In HIFU, highly intensive ultrasound waves trigger hyperthermia in the tumor tissue, which ultimately leads to maximum destruction of the tumor. Cryotherapy, on the other hand, uses cryoprobes through which liquid argon is introduced into the tumor, which then becomes "frozen" and necrotic. Photodynamic therapy uses light-sensitive dyes that become active after stimulation with laser light and trigger hypoxia and vasoconstriction in the tumor to kill it. Finally, in IRE, doctors use high electrical voltages to damage the degenerative cells.

Advantages of FT

The reason why FT, despite the still insufficient evidence, is already seeing growing popularity in everyday practice is that it focuses on the tumor while protecting the rest of the prostate. In fact, the success of FT cannot be dismissed, especially in comparison to radical prostatectomy.

Incontinence rates of < 2% or the occurrence of erectile dysfunction in only 5-20% of patients speak for themselves. Nevertheless, the current guidelines of the European Association of Urologists (EAU) also limit the euphoria over approach: FT is still an experimental therapy method, the use of which is not recommended outside of medical studies.

However, more and more patients are asking for this gentler prostate cancer treatment and more and more urologists are making this method available to a strictly selected group of patients. But what happens if the FT fails in the end and the patient has tumor progression?

After FT failure: What to do?

Due to the limited data basis (several case series and only 1 RCT) for FT, neither studies nor expert consensus currently recommends how to deal with FT failure. For urologists, this ultimately means that they have to go on "thin ice" in terms of medical law.

Since Prostate-Specific Antigen (PSA) monitoring was not validated for FT, only imaging procedures and prostate biopsies remain every 6-12 months to check the success of the treatment. However, the literature shows that up to 25% of patients receive a positive biopsy during these follow-ups. In some cases, this is a new tumor focus, in others, however, it is a "forgotten" tumor of the primary outbreak.

The treating urologists now have the following options for further treatment, but none of these have been examined as a second line after an unsuccessful FT:

  1. Active surveillance,
  2. Renewed FT of the area concerned,
  3. Ablation of the prostate using various procedures,
  4. Salvage radiotherapy,
  5. Salvage radical prostatectomy.

However, the available studies on this topic (1 review with 4 studies) suggest that salvage procedures after FT always have a worse prognostic outcome than these procedures in first-line therapy. For example, when salvage treatment was performed between 3 and 48 months after FT, the biochemical recurrence of PCa was 32.8%. Continence could then only be maintained in about 57% of the patients and only 4.4% of the men treated with Salvage reported satisfactory erectile function.      


If there is progress or recurrence of tumor foci after FT, the data available so far is not sufficient to provide recommendations for rational further treatment of these patients. Nevertheless, salvage radical prostatectomy seems to be quite suitable and safe.

However, patients who wish to undergo radical prostatectomy after unsuccessful FT salvage should be advised that such a procedure is associated with a higher degree of erectile dysfunction and shortened failure-free survival.