Prostate Cancer Focal Therapy Has Made Great Strides and the Future Remains Bright

Polascik is a professor of Surgery/Urology and director of Focal Therapy at the Duke Cancer Center, Duke Medical Center in Durham, NC

Although partial-gland therapies, also known as focal therapies, have been incorporated into the surgical treatment pathway of nearly every solid organ system, the prostate has been particularly challenging due mainly to 2 concerns: cancer multifocality and the difficulties of accurately imaging the boundaries of a distinct tumor(s) as typically occurs in other organs, such as the kidney. Despite these challenges, however, the slow but steady acceptance of the concept of focal therapy for prostate cancer has been growing over the past 2 decades, with gratitude to the dedicated individuals who have had the foresight to propel focal therapy to eventually become a standard treatment for select men. Support for the development of image-targeted interventions is also extended to our industry partners and collaborative scientists who continue to push the envelope on technical enhancements and new discoveries that aid in the detection, characterization, and image-guided treatment of such neoplasms.

With the widespread adoption of multiparametric MRI, we now have a reliable imaging platform to direct patient selection and provide intraprocedural guidance and posttherapy surveillance.¹ MRI still leaves room for improvement, though, as up to 15% of tumors are MRI-invisible and the 3-dimensional shape of each cancer with precise determination of the boundaries leaves room for discovery.^2,3 Also, over the past 2 decades, physicians and patients have become more comfortable with the management of multifocality, provided that untreated, small, and indolent satellite tumors can be confidently monitored and do not pose a threat to a patient’s life expectancy.

As the authors discuss, a number of short- to medium-term outcomes have been reported on primary focal therapy, ranging from single-institution and multicenter series to small clinical trials.⁴ From a functional point of view, most would agree that the results of focal therapy overall have been exceptional at preserving urinary function and continence. Potency outcomes have also been very competitive with, if not better than, traditional whole-gland therapies. However, cancer control has yet to demonstrate mature long-term data. Regarding oncologic outcomes, the reality is that even traditional therapies such as radiation and surgery have failure rates and certainly have adverse effects on the quality of life of many men. We should not expect focal therapy to improve the failure rate when compared with whole-gland therapy. Since it is a partial gland therapy, a consensus panel believed that retreatment rates up to 20% with focal therapy were clinically acceptable.5 Further therapy may be required if a targeted ablation does not control a clinically significant tumor, and other men may require additional treatment if a de novo, or out-of-field, tumor is subsequently detected and deemed in need of therapy during follow-up.

Several ablative devices are on the market, some of which combine physical ablation with targeted drug/device therapy. This takes on yet another challenge when determining efficacy of focal therapy, as new devices and treatments will similarly be introduced over time. We need a means to address the effectiveness of these treatments, particularly in situations where the natural history of prostate cancer is often prolonged, requiring in excess of 10 years to determine oncologic outcomes. For the most part, clearly functional outcomes can be assessed in the short term, and the data to date have been very supportive of focal ablation.^4,5

Patient selection remains the cornerstone of properly applied focal therapy. With the well-chosen tumor/patient, many will be able to avoid radical treatment in the intermediate term while preserving genitourinary function. If this goal can be realized, it should be understood that a limited percentage of men may require an additional ablation at some point that may be reasonable as long as the cancer can continue to be controlled and quality of life maintained. We have already seen this in the renal literature, where a small percentage of patients will require a second ablation for treatment of a small T1a renal cell carcinoma, and this has been accepted by most practitioners and patients.

As we move forward with collecting long-term cancer outcomes, it is important to be mindful that patient and tumor selection remain the cornerstone of successful partial-gland ablation. Finally, it is important to be forthcoming with patients regarding the intended goals, benefits, and limitations of focal therapy, and to have them understand that retreatment, identification of de novo tumors, or progression is always possible.

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

References

1. Lebastchi AH, George AK, Polascik TJ, et al. Standardized nomenclature and surveillance methodologies after focal therapy and partial gland ablation for localized prostate cancer: an international multidisciplinary consensus. Eur Urol. 2020;78(3):371-378. doi:10.1016/j.eururo.2020.05.018

2. Duvnjak P, Schulman AA, Holtz JN, Huang J, Polascik TJ, Gupta RT. Multiparametric prostate MR imaging: impact on clinical staging and decision making. Urol Clin North Am. 2018;45(3):455-466. doi:10.1016/j.ucl.2018.03.010

3. Westphalen AC, McCulloch CE, Anaokar JM, et al. Variability of the positive predictive value of PI-RADS for prostate MRI across 26 centers: experience of the Society of Abdominal Radiology prostate cancer disease-focused panel. Radiology. 2020;296(1):76-84. doi:10.1148/radiol.2020190646

4. Tourinho-Barbosa RR, Wood BJ, Abreu AL, et al. Current state of image-guided focal therapy for prostate cancer. World J Urol. Published online May 22, 2020. doi:10.1007/s00345-020-03254-4

5. Donaldson IA, Alonzi R, Barratt D, et al. Focal therapy: patients, interventions, and outcomes—a report from a consensus meeting. Eur Urol. 2015;67(4):771-777. doi:10.1016/j.eururo.2014.09.018