The Prostate Photodynamic Therapy has been evaluated in different types of study were the prostate cancer presentation was different. Regarding prostate cancer the most important criteria are the aggressivity of the disease expresses by the ISUP classification (see “Clinical Scenarii”), the PSA and the TNM classification (see “Diagnostic Tools”).
- Phase II
In the 3 phases II (2 in Europe and 1 in the US) the indications are the same. All the patient presented an ISUP 1 with a number of positive biopsies below 5 and less than 50% invasion of each core. The PSA was below 10 ng/ml. Even if on the digital rectal examination a small nodule could be detected only on one lobe classifying the tumour as T2a, biopsies on both sides (bilateral cancer) were accepted [26, 30].
- Phase IIb
Conducted in Latin America, the LATAM study was a confirmatory phase II study performed in Mexico, Panama and Peru. Most of the patients were ISUP 1 uni- or bilateral. However ISUP 2 patients were accepted with a PSA up to 20 ng/ml. The clinical stage was similar to the phases 2 .
- European Medicine Agency (EMA)
In the approval of the photosensitizer (Tookad®), the EMA opted for ISUP 1, PSA below 10 ng/ml and a clinical stage up to T2a. Regarding the biopsies the criteria are complicated however with a PSA density above 0.15 the number of positive cores is not an issue while the tumour has to be unilateral.
The presentation «Indications » provides a summary of the criteria used during the different studies evaluating the Prostate Photodynamic Therapy on variable populations through the world (video 13).
Video 13 : Indications of the Prostate Photodynamic Therapy
Prostate Photodynamic Therapy is the unique focal therapy to have produced the highest level of evidence in a scientific study. Three different parameters are of huge importance when a prostate cancer treatment is evaluated.
- Cancer Control
Cancer control, erection and continence are the main issue socalled trifecta when reached. Regarding cancer control whatever the phase II or phase 3 socalled randomized clinical trial (highest level of evidence), the results are reproducible around 80-85% of negative biopsies in the targeted area whether ISUP 1 or 2 uni- or bilateral. Compared to the active surveillance the risk of progression was divided by two at 2 years follow-up and was maintained at 5 years. Far more important, after a Prostate Photodynamic Therapy, the risk of conversion to a radical treatment compared to active surveillance was divided by 5 at 2 years and by 2 at 5 years avoiding the heavy side-effects of a radical treatment for a majority of men. After a Prostate Photodynamic Therapy if a radical prostatectomy was still needed, the procedure was feasible without particular problems. However if possible a brachytherapy was advised in order to keep the prostate in place and to reduce the side effects as much as possible.
Compared to a non-interventional treatment (active surveillance), in all the studies, Prostate Photodynamic Therapy had similar results in terms of erection and continence. At the request of the European Medicine Agency (EMA), a simulated statistical analysis based on a modelling shows that compared to radical prostatectomy (RP) or active surveillance (AS), Prostate Photodynamic Therapy presented at 5 years the best rate of erection preservation (-31% vs AS and -79% vs RP) and incontinence risk (-62% vs AS and -88% vs RP). All these results are well summarized in the presentation « Results ». In practice, 85% of the patients treated maintained their erections and depending on the amount of prostatic tissue preserved an ejaculation (video 14).
Video 14 : Results of the Prostate Photodynamic Therapy