By: Dan Sperling, MD

Conventional first-line therapies for prostate cancer are generally directed at the entire gland: either surgically remove it (prostatectomy), or radiate it with one of several types of beam radiation or seed implants. In the majority of cases, cancer control is achieved. However, after treatment all patients must periodically monitor for recurrence, usually through a PSA blood test at prescribed intervals. In the case of radical prostatectomy (RP) which leaves behind no prostate cells to produce PSA, any detectable post-surgery PSA is suspicious of recurrence. In the case of radiation, in which PSA eventually settles to its nadir (lowest post-treatment value), any rise in PSA above nadir is likewise suspicious of recurrence. While specific definitions vary, rising PSA is considered an indication of biochemical failure, meaning the prostate cancer was not completely eradicated by the treatment and is now progressing in the body. The relevant question becomes, “Where is it?”

Following RP, the recurrence rates at 15 years have been shown to be 10% for low risk disease, and as high as 50% for high risk disease. If it can be confirmed that there is local recurrence (the area of the prostate bed where the gland was removed), radiation therapy (RT) may be offered as a salvage treatment with potential for cure. On the other hand, if the recurrence is identified in more remote areas such as lymph nodes, bone, or other organ, it would make little clinical or economic sense to radiate the pelvic bed when a systemic treatment such as hormone blockade might be better indicated. However, PSA value does not necessarily correlate with the location, amount, or aggression level of post-RP recurrence, so a better detection method is necessary to determine appropriate treatment.

Following RT, the 5-year recurrence rates range from 15% for low risk disease to 67% for high risk disease. Determining recurrence—and its location—is more complicated than post-RP because different amounts of PSA-producing tissue can be present depending on the method and dose of radiation. The rate at which PSA rises above nadir may provide a clue to recurrence: a rapidly rising value suggests remote metastasis, whereas a slowly rising value is more likely to indicate local recurrence. Again, location determines the treatment plan: salvage options for localized recurrence include prostatectomy or minimally invasive thermal ablation, whereas systemic treatment is appropriate for remote spread. In either case, PSA is still not entirely reliable as an indicator of recurrence.

A recent literature review discusses the merits of multiparametric MRI (mpMRI) for detecting the return of prostate cancer following whole gland treatment.[i] The authors broadly note that mpMRI is “the most useful tool available” for detecting localized recurrence, even very small tumors, following both RP and RT. They make their case by summarizing numerous published studies, divided into one section of mpMRI after surgery, and the other section on mpMRI after radiation. They point out that information derived from mpMRI is gained from four parameters that assess functional differences between normal and cancer tissue: T2 weighted images, diffusion weighted images, dynamic contrast enhanced images, and MRI spectroscopy. In patients with higher PSA values, the additional use of PET/CT scans, especially with today’s advances, may be used to scan for more distant recurrence in the lymph nodes or other sites. Because both RP and RT generate scarring and other tissue changes, mpMRI is of particular value in the pelvic bed because of its sensitivity and specificity in distinguishing localized cancer from other tissue formations.

Following RP, if detectable PSA occurs, it is essential to obtain positive diagnosis of prostate bed recurrence, and rule out distant metastasis. This permits accurate planning of salvage RT to the region containing the tumor, thereby reducing the potentially toxic impact of radiation on nearby healthy structures (bladder, rectum, and colon).

In the case of recurrence following RT, precision imaging by mpMRI can likewise inform a more targeted treatment approach. Traditionally, salvage therapies (surgery or ablation) have been directed at the entire gland because biopsy alone was insufficient for confident assessment of the tumor size, shape and location. However, it is increasingly possible to deliver image-guided focal ablation as a result of mpMRI evaluation. Focal salvage therapy offers reduced risk of urinary and sexual impairment.

In closing, the authors urge that mpMRI be applied quickly upon suspicion of recurrence, in order to maximize the opportunity for an effective local treatment before the cancer can spread further.

[i] Barchetti F and Panebianco V. Multiparametric MRI for 5ecurrent prostate cancer post radical prostatectomy and postradiation therapy. BioMed Res Internat. 2014;Vol 2014, Article ID 316272:23 pp. Full article at www.hindawi.com/journals/bmri/2014/316272/