Case study 115.1
Low-Risk Disease
A 65-year-old male with an elevated prostate-specific antigen (PSA) of 5.7 ng/dl underwent a prostate biopsy revealing one core Gleason 6 disease in the right midprostate and one core Gleason 6 left base; both cores are <50% involved.
1. What treatment should this patient undergo?
- Brachytherapy
- External-beam radiation with hormone therapy
- Radical prostatectomy
- Active surveillance
It is important for the clinician to discuss the necessity for intervention with patients before discussing details of different treatment modalities, hence the consideration for active surveillance among the answer choices. The recently published Prostate Intervention versus Observation (PIVOT) trial is a good place to begin this discussion. This study evaluated over 700 men with PSA-detected locally confined prostate cancer and randomized them to treatment versus observation with a primary endpoint of all-cause mortality. The authors concluded that in men diagnosed with prostate cancer in the early PSA era, at 12 years of follow-up, prostatectomy did not improve all-cause or prostate cancer–specific mortality over observation. However, to apply the findings of the overall study to this patient, one must delve further, which we will consider again in another vignette in this chapter. The lack of treatment effect from the PIVOT trial most strongly applies to patients with Gleason grade (GG) <7 and PSA ≤10 who were ≥65 years of age, as seen visually when looking at the forest plots from the study. These findings are in concert with other studies showing that in many men with low-risk prostate cancer, active surveillance should be the treatment of choice. There are slight variations for inclusion criteria and definition of progression, but all stress the concept that men with low-grade disease should be offered a trial of active surveillance with the ability to intervene at the first signs of progression.
The patient and his wife were extensively counseled about active surveillance; however, they were both very uncomfortable with this option, each having witnessed family members die from cancer. They are having a hard time believing that you can just “watch” cancer.
2. What minimally invasive treatment options exist for this patient besides the more standard options of radiation or surgery?
- Focal cryoablation
- Focal high-intensity focused ultrasound (HIFU)
- Focal laser therapy
Any of the above focal treatments is an option in the setting of an Institutional Review Board–approved clinical trial. This patient does have multifocal, bilateral disease, and thus the appropriateness of a focal approach depends on the goal of treatment and the ability to determine the most clinically significant lesion.
There are centers offering focal treatment for prostate cancer outside the setting of a clinical trial; however, with low patient numbers, limited follow-up, and nonstandardized methods for determining effectiveness, it must be carefully applied. This is best accomplished through the confines of a clinical trial, and this is especially true for focal HIFU in the United States as it is not currently approved by the US Food and Drug Administration (FDA).
This patient would not necessarily be excluded from focal treatment because of its multifocality. If utilizing improved imaging (e.g., endorectal magnetic resonance imaging (MRI) or color Doppler ultrasound) and biopsy targeting, a clinician can determine which of the lesions within the prostate is clinically significant, in which case focal treatment may be a sound option. The determination of the “index” lesion might be based on tumor size, grade, or growth rate. Studies evaluating tumor volume have estimated an increased risk of disease progression in a lesion 5 mm, and have correlated positive surgical margins and extraprostatic extension to the “index” or largest lesion. Therefore, an argument can be made for treating an index lesion with focal therapy while continuing active surveillance of smaller, clinically low-risk or very-low-risk lesions. This would allow for minimizing side effects, with the possibility of future treatments if needed. If, in contrast, the treatment goal is complete disease eradication, then a patient with multifocal bilateral disease would represent poor patient selection.
• If you are going to treat this patient with a focal treatment, how can you be sure that his disease is accurately staged and graded?
This is a very real concern for those treating prostate cancer. When using most preoperative nomograms, the most important prognostic variable is the Gleason grade (GG). These nomograms are important tools for physicians and patients in counseling; however, some patients are not appropriately counseled as to the risk of upgrading from the biopsy results. Estimates of the rate of upgrading after radical prostatectomy are between 24% and 61% and upstaging at 7–19% for extracapsular extension and 2–9% for seminal vesicle invasion. One potential way to improve these results is through better imaging, including functional and molecular modalities. Multiple studies, including several from our center, have identified multiparametric MRI’s (mpMRI) ability to improve prostate cancer detection compared to grayscale transrectal ultrasound (TRUS) biopsy, correlate suspicion level with D’Amico risk group, localize imaged lesions to true disease burden on whole-mount pathology sections, and potentially decrease the rate of upgrading or upstaging at prostatectomy. There have also been advances in grayscale ultrasound, including color Doppler and contrast-enhanced modalities that have shown promise in early trials.
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