Prostate Cancer: Defining Clinically Significant Disease
Peter Choyke1

1National Cancer Institute, United States


The goal of performing MRI in prostate cancer is to help distinguish indolent, low risk prostate cancers from those harboring clinically significant features. This presentation reviews the criteria for clinically significant tumors and underscores the benefits that accrue when using MRI as a gateway for the diagnosis of prostate cancer.

Clinically Significant Prostate Cancer

Prostate cancer represents a broad range of tumors including clinically indolent and highly aggressive. The term "clinically significant" is actually not completely agreed upon. It is supposed to indicate that a particular tumor has a reasonable chance of leading to death due to prostate cancer. It is perhaps easier to define what is not "clinically significant". Tumors with low Gleason score (i.e. 3+3) and low volume (<0.5cc) and low PSA (<10ng/ml) are considered low risk and such patients are typically offered active surveillance. Some centers also include in this category low-intermediate Gleason Scores (i.e. 3+4) provided the volume is low and the PSA is low and the percentage of grade 4 is low (typically less than 20%). These data are based on very low recurrence rates in patients undergoing surgery for such lesions. One common source of misunderstanding is that a risk assignment speaks only to the current situation not a future situation. So, at the time of diagnosis the risk of metastatic disease from a Gleason 3+3 or 3+4 tumor is very low. However, over time such a tumor could evolve and therefore, must be monitored. It is not uncommon for a patient to evolve from a non-significant tumor to a clinically significant tumor over time. Thus, the current status of a tumor is not necessarily representative of the future status.

Thus, tumors above low or low intermediate risk are generally considered clinically significant. This term should be used guardedly as it is meant to convey that treatment will benefit the patient. This is far from proven. In patients with intermediate-high and high risk tumors rates of progression are slow but typically, if left untreated, the tumor will progress over a period of years. If the patient has an intercurrent illness or other risk factors, even a "clinically significant" tumor may not be the cause of death. Moreover, it has not been established that immediate treatment is always necessary and that delays in treatment can be offered without increasing the risk of prostate cancer death.

MRI has offered a new method of detecting clinically significant tumors without incurring added risks of detecting more low risk tumors. For instance, Siddiqui et al showed that MRI provided a 30% increase in the detection of clinically significant prostate cancer and a 17% decrease in indolent cancer detection when compared to random biopsies. The PRECISION trial recently showed a 13% increase in the detection of clinically significant cancers and a 12% decrease in indolent cancers using MRI vs. conventional biopsy. Moreover, in that study 28% of patients avoided biopsy altogether due to negative MRI scans.

Factors associated with clinically significant tumors include PSA, PIRADS score, lesion size, location, presence of extraprostatic extension or seminal vesicle invasion and ADC values. The presence of a PIRADS 4 or 5 lesion indicates the need for an image guided biopsy based on the high likelihood of finding a clinically significant tumor. Nonetheless, a sizeable percentage of ominous looking lesions are negative for tumor or demonstrate low Gleason scores. In such cases, consideration should be given to early rebiopsy as the chance of a miss during a MRI guided biopsy is high. Consideration in such cases should be given to the quality of the MRI, its interpretation, the quality of the MRI-TRUS registration and notes of any technical difficulties during the biopsy. Careful attention to such details result in much better yields from MR guided biopsy and fewer false negatives.

The goal of introducing MRI into the diagnostic workup of patients suspected of prostate cancer is to identify those patients with clinically significant cancers who are most likely to benefit from aggressive treatment while minimizing the diagnosis of indolent low grade tumors that lead to consternation and uncertainty but whose diagnosis is of no benefit to the patient. Hopefully, over time, we will get better at distinguishing lesions that must be treated from lesions that can be monitored


The author wishes to acknowledge his colleagues: Baris Turkbey, Peter Pinto and Brad Wood and the support of the intramural program of the National Cancer Institute, Bethesda, Maryland, USA


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Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)