Photodynamic Therapy with TOOKAD®

A new approach to focal treatment for prostate cancer has made its entrance onto the world stage and has patients talking. It is called photodynamic therapy (photo for light, dynamic for action) or PDT. It involves administering a light-sensitive chemical called TOOKAD® by a 10-minute IV injection, which is quickly taken up in the prostate gland. For focal PDT, either MRI or ultrasound imaging is used to identify the tumor location. However, for the procedure itself, ultrasound imaging is the basis for the special software that calculates the number and location of laser fibers to be used, and these are inserted through the perineum into the gland under transrectal ultrasound guidance. At the end of the 10 minute IV infusion, the lasers are switched on. This activates the TOOKAD. It then interacts with the cancer cells in a way that destroys the cell membrane and interferes with enzyme processes, so the tumor cells die. Following treatment, TOOKAD’s manufacturer (Steba Biotech) states that the drug is “totally eliminated, with no toxic residue, three to four hours after the 90-minute procedure.”[i] TOOKAD is not yet approved for use in the U.S., but several international clinical trials have been testing its safety and efficacy. Following an 80-patient clinical trial in Latin American, Mexico granted approval for its use in the spring of 2016.

The PDT procedure averages 1.5-2 hours. It is done under general anesthesia without exception, since there can be absolutely no patient movement during placement of the laser fibers or once the fibers are placed. If movement occurs, the fibers must be removed and placed again. In order to facilitate clear ultrasound images of the gland, a urinary catheter is inserted and clamped to keep a full bladder during the procedure (it can be removed 3-4 hours after). Also, since TOOKAD is given intravenously, it diffuses through the entire body, not just the prostate. Therefore, the operating room is darkened (except for the perineal area) during the procedure; the patient is completely draped and wears protective goggles; as a safety precaution the patient is kept covered and remains in dimmed light for 6 hours before discharge from the surgery center; and the patient is advised to avoid direct sunlight for 48 hours after PDT. Deviating from any of these measures can result in damage to tissue exposed to strong light.

A larger European randomized trial of low-risk prostate cancer patients compared PDT vs. active surveillance in terms of disease progression. Over 400 patients were involved: 206 were assigned to the PDT group and 207 to active surveillance. According to a March 16, 2016 report, “Patients were followed-up during a 2-year period, with measurements of prostate-specific antigen (PSA) and urinary and erectile functions every 3 months, plus biopsies at 12 and 24 months.”[ii] The study authors found that at 24 months after treatment, 14% of the PDT group had positive biopsies, compared with 49% of the active surveillance group. From this, the authors concluded that PDT was “effective at reducing rates of progression, conferring a negative biopsy status, and diminishing the need for radical therapy.”[iii]  It was noted that there were no genitourinary side effects such as incontinence or erectile dysfunction among the PDT group.

While PDT appears to be promising, it is important to recognize that the European study compared intervention (PDT) with no intervention (active surveillance), and that there is very little statistical data beyond this study. While there are numerous published articles tracing its development and promise, it is difficult to get a sense of how effective it is, and how durable its cancer control. A 2015 article that describes current treatment standardization “based on the experience gained through hundreds of procedures” is well-detailed but lacks any data on the outcomes or side effects of the procedure – which is disappointing.

Finally, despite improvements in transrectal ultrasound imaging guidance, that technology simply cannot provide the precise, high-resolution anatomic and functional information that multiparametric MRI gives. There can be no doubt that for prostate treatment, MRI guidance and thermometry such as we use for focal laser ablation is today’s state of the art, and tomorrow’s standard.

In the meantime, we will be paying attention to developments in PDT, and curious to see if the procedure evolves into one that can be done under MRI guidance. We would expect that the precision and therefore effectiveness of PDT would be improved if that comes to pass.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] http://www.weizmann-usa.org/media/2016/04/11/revolutionary-therapy-for-prostate-cancer-coming-to-europe
[ii] http://www.firstwordpharma.com/node/1366390#axzz45W82GmIP
[iii] https://prostatecancerinfolink.net/2016/04/11/new-form-of-focal-therapy-approved-for-treatment-of-low-risk-prostate-cancer/