Prostate cancer is one of the most common noncutaneous cancers and the second-leading cause of cancer mortality in American men. Clinically localized prostate cancer accounts for most new cancer diagnoses, with an estimated 91% of new cases diagnosed at local or regional stages.
"Traditionally, we had been treating with radical prostatectomy or by radiating the entire prostate. Now, since we aren’t treating the whole gland, we don’t have the safety net of automatically treating any other tumors throughout the gland that may not have been detected on diagnostic imaging or biopsy."
Traditional treatment options for localized disease vary widely, from watchful waiting or active surveillance to aggressive treatment with surgery, radiation therapy or brachytherapy. Aggressive therapy could offer the opportunity for cure, but also often leads to side effects that can significantly affect quality of life, including erectile dysfunction, urinary incontinence and bowel dysfunction.
The team at Cedars-Sinai is determined to find a way to treat clinically localized prostate cancer while minimizing debilitating side effects and ensuring the whole gland is cancer free.
The advent of focal therapy
Recent strides in technology have made it possible to precisely target treatment of localized prostate cancer to the cancer itself, while sparing the rest of the prostate. This approach limits side effects related to damage to surrounding structures.
Timothy J. Daskivich, MD
"Focal therapy became a viable treatment strategy when HIFU—high intensity focused ultrasound—was approved by the FDA in 2015," says Timothy Daskivich, MD, a urologic surgeon at Cedars-Sinai. "It has been a game-changing, novel treatment approach that allows us to treat exactly where the cancer is while sparing the anatomical structure around the prostate to minimize side effects and preserve quality of life."
However, this targeted treatment modality increases the stakes for ensuring that there is no cancer outside of the specific area being treated.
"Traditionally, we had been treating with radical prostatectomy or by radiating the entire prostate," says Daskivich. "Now, since we aren’t treating the whole gland, we don’t have the safety net of automatically treating any other tumors throughout the gland that may not have been detected on diagnostic imaging or biopsy. We need to improve our diagnostic capabilities and use all of them to the fullest potential to make sure we catch and treat cancer on all sides of the gland."
To identify any cancer on the side of the gland not currently being treated, physicians do an MRI and biopsy. If no cancer is detected through these methods, it is assumed there is none present. But data shows there is a 10% to 15% false negative rate for prostate MRI and the miss rate for cancer with systemic biopsy is even higher.
"Given the false negative rate that keeps us from catching cancer on the other side of the gland, we thought using a prostate-specific PET tracer would allow us to capture disease missed by the MRI, identify it before focal therapy, and potentially change the treatment pattern as needed," says Daskivich.
The team has already completed one project using a PET tracer called Axumin. It revealed cancers previously missed by both MRI and biopsy, prompting an alteration of the HIFU treatment pattern in impacted patients to address all the identified cancer.
Another step forward
Building on that initial success, researchers are now taking a look at a different PET tracer—PSMA—that has better diagnostic characteristics as it is even more specific and sensitive.
"We are repeating the protocol we've previously done using PSMA PET," says Daskivich. "We're using PSMA PET to augment the ability of MRI to identify clinically significant cancer to map out all of the tumor, so we don't miss anything with focal treatment. We really think the approach of using both MRI and PET in conjunction with one another is going to improve our ability to maximally detect clinically significant cancer that's meaningful to treat."
Even if this new diagnostic method does not result in a change in treatment right away, it could detect low-grade Gleason 6 cancer that should be monitored closely moving forward.
"MRI is not great at detecting Gleason 6 cancer, and with focal therapy it's important to know there is cancer that needs monitoring on the other side of the gland," says Daskivich. "For example, if you do focal therapy for a high-grade cancer but PSAs don't go down after the procedure—that can be hard to explain. But if you know there is cancer on the other side, it might help you better interpret surveillance."
The idea of detection and tumor mapping before HIFU has consequences not just for the HIFU treatment itself, but for surveillance afterward. If a patient has known Gleason 6 cancer on the side of the prostate gland opposite the HIFU treatment, it needs to be monitored in a dedicated way.
Recruitment is underway for the trial with results expected within the next year.
The scale of success
Cedars-Sinai is uniquely positioned to evaluate this technology as the development site of the high-resolution MRI scan used in the study. It provides fivefold improved resolution compared with standard multiparametric MRI. Cedars-Sinai is also one of only a few organizations with access to a PET MRI scanner.
"The biggest potential benefit of HIFU is for patients with high-grade disease localized to one side of the prostate who are candidates for hemigland or focal treatment," says Daskivich. "If there is high-grade disease on both sides, total gland HIFU is likely to result in similar side effects as with traditional therapies."
Perhaps the biggest question on the table is the potential impact scale of the research itself. Daskivich believes HIFU will become the standard of care for patients with unilateral Gleason 7 disease. Patients with Gleason 6 are often watched on active surveillance, while patients with Gleason 8 or higher need more invasive therapies to maximally get the cancer out.
"Whether or not this is used in practice will in part depend on the scale of the benefit—that’s what we’re testing," says Daskivich. "We don’t yet know how often the technology will change the treatment plan for HIFU and how many patients it will make ineligible for HIFU based on detection of high-grade disease on the other side of the gland," says Daskivich.
Ultimately, the goal is to determine how to best use these incremental advances in hyperaccurate detection to cure cancer.
Read Invention: A Blood Test to Unlock Prostate Cancer Mysteries for more information.