Sperling Prostate Center

What is the Index Lesion Theory?

It has been suggested that in multifocal prostate cancer (PCa), focal therapy to the largest (index) lesion is sufficient, because secondary non-index lesions are unlikely to contribute to disease progression.[i]

In the world of urology, the belief that prostate cancer (PCa) is a multifocal disease has long dominated diagnosis and treatment decisions. Thus, treating PCa with curative intent involved a radical (whole gland) approach. Both surgical removal and radiation therapies were aggressively aimed at the entire prostate in hopes of eradicating all the cancer. The predominant belief determined this approach, but it left untold numbers of men with incontinence and sexual dysfunction. There’s a saying that applies here: if the only tool you have is a hammer, you’ll see every problem as a nail. But the hammer hits where it hurts.

For well over a decade now, evidence from prostatectomy specimens has suggested a need to enlarge the toolkit:

  • At least 25% of PCa cases appear to be truly unifocal, with a single lesion (tumor), and
  • The key determinant in treatment selection is the index lesion. The index lesion is defined as “the lesion(s) with the highest cancer suspicion score based on initial MP-MRI of a patient, irrespective of size.”[ii] In other words, treatment should be appropriate to the most aggressive lesion, and in some cases, there can be more than one lesion of equal aggressiveness—that is, more than one index lesion.

In one study of multifocal PCa, over 99% of the non-index satellite lesions had Gleason score total less than or equal to six,[iii] which is considered to be insignificant PCa that is not likely to become lethal during the patient’s lifetime. These lesions are amenable to Active Surveillance (AS) rather than immediate treatment.

The index lesion theory and focal therapy

In 2009, the journal Nature published an important article stating that cases of PCa metastasis spring from a single aggressive parent PCa cell that duplicates itself. The theory of the index lesion posits that such a cell is harbored either within a lone (unifocal) tumor, or within the index lesion(s) in cases of more than one tumor in the gland.

If so, then the hammer approach to obliterating the whole gland is overkill in many cases. Strategically, Focal Laser Ablation (FLA) of the index lesion(s) immediately destroys it—and the potentially dangerous cancer cells it contains—while sparing as much of the prostate as possible. More than one index lesion can be treated during the same session. FLA provides a high degree of confidence that the destruction is complete. Two main factors warrant this confidence:

  1. Accurate identification of the index lesion(s) using multiparametric MRI, along with in-bore MRi targeted biopsy to diagnose and characterize the PCa based on tissue analysis.
  2. During the FLA procedure, real-time visual treatment monitoring using specialized software confirms the zone of ablation, the lethal temperature, and a margin of safety.

FLA enlarges the PCa treatment toolkit, achieving a middle ground between radical treatment and AS. In fact, many patients who are well-qualified for AS shy away from it because they don’t like the idea of active PCa in their body. FLA of the index lesion(s) offers them eradication of the PCa while sparing their urinary and sexual function. This preserves quality of life as well as peace of mind.

Given the index lesion theory, more PCa patients are eligible than one might think. According to the study mentioned above, of the 100 prostatectomy specimens that were analyzed for index and non index lesions, 51% of those cases would have been eligible for focal treatment of the index lesion.

However, due to the lack of long-term, high level (randomized, controlled) research studies, there is still some skepticism in the urologic community. In a 2019 article, a team of multinational European authors write, “…due to the lack of consistent and long-term results and the presence of several difficulties in providing standardized treatment and follow-up strategies, [focal therapy] has been proposed by the European Association of Urology as an investigational modality.”[iv]

There is no question that prospective studies with a large number of participants are needed to satisfy the professional and academic demand for evidence. Nevertheless, the grassroots world of patients presents a different demand: manage our cancer but leave us whole as men. Just as occurred in women’s health when breast lumpectomy did not yet have a long-range track record but women opted for it anyway—as it turned out, their gamble was rewarded—men are pinning their hopes on focal treatments like FLA. At the Sperling Prostate Center, we see their hopes rewarded every day as we precisely ablate their index lesions plus a margin of safety. For more information on MRI-guided FLA, visit our website.

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.

[i] Karavitakis, M., Winkler, M., Abel, P. et al. Histological characteristics of the index lesion in whole-mount radical prostatectomy specimens: implications for focal therapy. Prostate Cancer Prostatic Dis 14, 46–52 (2011).
[ii] Rais-Bahrami S, Turkbey B, Rastinehad A, Walton-Diaz A et al. Natural history of small index lesions suspicious for prostate cancer on multiparametric MRI: recommendations for interval imaging follow-up. Diagn Interv Radiol. 2014 Jul-Aug; 20(4): 293–298.
[iii] Ibid.
[iv] Stabile A, Moschini M, Montorsi F, Cathelineau X, Sanchez-Salas R. Focal therapy for prostate cancer – index lesion treatment vs. hemiablation. A matter of definition. Int Braz J Urol. 2019;45(5):873-876.


About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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