A 65-year-old healthy man presented for management of low-risk prostate cancer. He was diagnosed a year prior, when his prostate-specific antigen (PSA) increased from 3 ng/mL to 5.6 ng/mL (free PSA 18%). A multiparametric MRI revealed a 47-cc prostate with a PI-RADS 2 lesion in the left anterior apex. Biopsy results indicated Gleason 6 in two systematic cores (80% left lateral mid, <5% left medial apex) and benign tissue with chronic inflammation in the targeted cores. The patient chose active surveillance (AS) and presented to our clinic a year later for evaluation.
The patient had a prior negative biopsy in 2008 when his PSA rose from 2.0 ng/mL to 3.3 ng/mL. Three years later, his PSA rose to 18 ng/mL during an episode of prostatitis and subsequently returned to baseline. Thereafter, his PSA remained in the 3s until it increased to 5.6 ng/mL, leading to the diagnosis of prostate cancer.
The patient was counseled about management options for low-risk prostate cancer, and he preferred to continue AS. However, he was concerned about the volume of low-risk cancer and opted to undergo the Oncotype DX genomic test (Genomic Health, Inc., Redwood City, CA) to obtain further information. His Genomic Prostate Score (GPS) came back at 32, with a 71% likelihood of favorable pathology (Figure 1).
Because the Oncotype DX results were consistent with the National Comprehensive Cancer Network (NCCN) low-risk category, the patient elected to continue AS. One year later, the PSA was 3.5 ng/mL and MRI showed persistence of the PI-RADS 2 lesion.
The patient underwent targeted biopsy, which showed Gleason 6 in two systematic cores and no cancer in the targeted cores.
The use of AS is increasing in the United States and internationally.1,2 Long-term data show favorable outcomes with this approach,3 and it is supported by multiple guidelines. In 2016, the American Society of Clinical Oncology (ASCO) endorsed the Cancer Care Ontario guidelines, recommending AS for most patients with low-risk (Gleason ≤6) prostate cancer.4 However, they acknowledge that there is heterogeneity within this risk category and that further consideration should be given to younger men, black men, and those with high-volume disease. For patients with low-risk prostate cancer and a life expectancy less than 5 years, they recommend watchful waiting.
Similarly, the 2017 American Urological Association/American Society for Radiation Oncology/American Society of Urologic Oncology (AUA/ASTRO/SUO) guidelines on localized prostate cancer recommend AS as the best available care option for very low-risk prostate cancer and as the preferable care option for most low-risk patients.5 The 2018 NCCN guidelines also recommend AS for patients with low-risk prostate cancer and a life expectancy of at least 10 years and observation for those with a life expectancy of less than 10 years.6
Each of these guidelines also includes recommendations about monitoring protocols during AS. ASCO recommends PSA tests every 3 to 6 months, DRE at least yearly, a ≥12-core confirmatory transrectal ultrasound–guided biopsy (including anterior directed cores) within 6 to 12 months after diagnosis, followed by serial biopsy every 2 to 5 years thereafter or more frequently if clinically warranted.4 Ancillary tests such as multiparametric MRI and markers are considered “still under investigation” but may be indicated when clinical findings are discordant with pathology findings and could be used to identify occult changes indicative of tumor progression. ASCO recommends that consideration be given to active therapy for patients with a surveillance biopsy showing a Gleason score of 7 or higher and/or significant increases in the volume of Gleason 6 tumor.
The 2017 AUA/ASTRO/SUO guidelines recommend routine surveillance PSA testing and DRE during AS.5 They encourage a confirmatory biopsy within the initial 2 years and surveillance biopsies thereafter. Multiparametric MRI may be considered as a component of AS. However, the guidelines state that genomic tissue markers have not shown a clear role in AS and are not necessary for follow-up.
Finally, the 2018 NCCN guidelines recommend serial PSA, DRE, and biopsy no more than every 6 months, no more than every 12 months, and no more than every 12 months, respectively, unless clinically indicated.6 They recommend considering multiparametric MRI if anterior and/or aggressive cancer is suspected when PSA increases and systematic biopsies are negative.
Molecular testing is not recommended for very low-risk disease but may be considered for low-risk patients. The guidelines panel acknowledged that the clinical utility of genomic tissue tests had not been assessed in prospective randomized trials but that retrospective studies show these tests provide prognostic information independent of the NCCN risk groups.
The genomic test used in this case, Oncotype DX, provides a GPS based on expression of genes from multiple prostate cancer pathways. This test estimates the likelihood of favorable versus adverse pathology if the patient were to have immediate prostatectomy.7 Prior studies have shown that Oncotype DX results can influence clinical decision making about AS versus radical treatment. For example, in a clinical utility study, the GPS disagreed with the clinical risk category in 39% of cases, and 18% of recommendations for treatment versus AS changed based on the results.8
Other marker tests that are also commercially available for use in biopsy tissue include Prolaris (Myriad Genetics, Salt Lake City, UT) and Decipher (GenomeDX Biosciences, Inc., Vancouver, BC, Canada). Prolaris is a panel of cell-cycle progression genes, which predicts the 10-year risk of prostate cancer death in men who are managed conservatively.9 Prolaris has also been shown in clinical utility studies to influence decision making about AS versus treatment.10 Decipher is a genomic classifier that includes 22 RNA expression biomarkers.11 This test has been used in patients with adverse pathology features at radical prostatectomy to predict the risk of metastatic progression and has been shown to reduce decisional conflict for patients deciding on secondary radiation therapy.12 More recently, the Decipher biopsy test was launched to aid in initial treatment decisions.13 Although long-term comparative effectiveness data are lacking for these tests, they may be useful in clinical practice for borderline cases or for those with a discrepancy in other clinical findings to provide greater confidence in management recommendations.
In the current case, the patient had volume reclassification but remained in the low-risk category. Follow-up data from the Prostate Cancer Research International Active Surveillance study showed that an increase in the number of positive cores with Gleason 6 cancer did not predict a higher risk of adverse pathology at radical prostatectomy.14 As a result, such an increase is now used as a trigger for further investigation for the presence of higher-grade disease rather than an immediate switch to treatment. In our patient, further investigation has failed to identify the presence of higher-grade disease. The patient’s preference is to avoid radical therapy if possible, and the presence of concordant Oncotype DX results led to greater confidence in his decision to remain on AS.