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Clinical Case Discussion: Intermediate-risk Prostate Cancer: The Case for Active Surveillance

By: Marc A. Dall’Eraa and Benjamin J. Daviesb

EU Focus, Volume 1 Issue 2, September 2015, Pages 208-209

Published online: 01 September 2015

Abstract Full Text Full Text PDF (72 KB)

Refers to article:

Case Presentation: Intermediate-risk Prostate Cancer in a Fit 66-year-old Man

Alberto Briganti

September 2015 (Vol. 1, Issue 2, pages 207 - 208)

Take Home Message

Active surveillance offers men the opportunity to defer immediate local treatment of low risk prostate cancer while preserving a highly functional quality of life. Novel biomarkers and imaging technology will enable physicians to better identify ideal candidates for this approach beyond traditional clinical characteristics.

1. Case details

This case represents a common problem for urologists. When considering this man's care, the key issues are the disease burden, our confidence in the measures of his performance status and life expectancy, and his goals for medical care (ie, the balance between cancer cure and impact on quality of life). This man appears to have good quality of life, no sexual or urinary problems, and normal life expectancy for his age.

2. Discussion

The standard of care in this case of a 66-yr-old man with intermediate-risk prostate cancer (PCa) is to offer local treatment based on current guidelines published by the European Association of Urology, the American Urological Association, and the National Comprehensive Cancer Network [1], [2], and [3]. Data from several large and mature studies demonstrate that his risks of dying from PCa with treatment are low, and his prognosis is excellent [4]. As such, one could question the default need for radical treatment with this cancer. A balanced discussion with the patient must include the facts that (immediate) radical treatment may affect his urinary function (ie, incontinence) and sexual function (ie, impotence). These conditions reduce quality of life, although they may be temporary rather than lifelong [5]. Alternatively, does this man with low prostate-specific antigen (PSA) density and a single core of Gleason 3 + 4 PCa require immediate treatment? Klotz et al recently reported updated results for men with low- and intermediate-risk disease managed with active surveillance (AS; median follow-up of 6.4 yr) [6]. Cause-specific survival for this group is high and similar to men with low- and intermediate-risk disease treated with surgery or radiation [7].

In the evolving care of men with PCa, it is not unreasonable to question whether immediate treatment is necessary. Other series have described outcomes from AS in men with intermediate-risk features and suggest that these patients are not necessarily at higher risk of progression than men with only low-risk features [8]. Although many men on AS will eventually undergo definitive treatment as higher risk features are identified with time, the fractions with truly indolent disease remain treatment free. This patient has a low PSA density with a low percentage of biopsy core involvement, features that are both associated with lower rates of progression or disease reclassification with surveillance [9]. Perhaps we should expand our criteria for offering an expectant approach with delayed intervention to men with more traditionally intermediate-risk features, particularly for healthy and highly functional men, such as in the case presented.

Proper counseling for this patient begins with risk stratification and assessment of patient priorities and expectations for treatment. Any risk that this cancer poses to his longevity if no immediate localized treatment is used must be balanced against the impact on sexual and urinary function as well as quality of life that may occur with treatment. The ultimate goals and priorities of therapy must be considered and individualized.

Physicians and patients express concern about the limitations of risk assessment based on information obtained from a single prostate biopsy session, in which tumor grade or stage may be underestimated up to 40% of the time [10]. If this patient considers surveillance, further risk assessment is recommended to limit this risk and to improve decision making. One option advocated by certain AS protocols is to offer an early repeat or “confirmatory” biopsy to improve prostate sampling for more significant disease. With this approach, up to 30% of men are found to have higher risk disease features for which immediate treatment may be more appropriate [11].

Multiparametric magnetic resonance imaging (mpMRI) is rapidly evolving as the imaging study of choice for characterizing localized PCa but must be integrated carefully into clinical practice by well-trained users. When comparing preoperative MRI findings with pathology after prostatectomy, Turkbey el al demonstrated 92% accuracy with MRI for predicting organ-confined low-risk cancers for which AS may be offered [12]. For men with low-risk PCa already diagnosed, techniques using mpMRI and repeat biopsy demonstrate high negative predictive values for detecting clinically significant disease, including Gleason 3 + 4 [13]. These early experiences suggest that a strategy using prostate MRI and targeted lesion biopsy for men considering AS can identify high-grade lesions; however, up to 8% of the time, higher grade tumors (predominant pattern ≥4) may not be detected by MRI alone [14]. Consequently, it is not clear whether systematic biopsy can be safely eliminated for men with negative MRI who are considering AS.

In this case, the patient underwent mpMRI and was found to have a Prostate Imaging Reporting and Data System class 3 lesion in the prostate, which is equivocal for carcinoma. This funding suggests a relatively low likelihood for higher grade or stage tumors in the prostate, based on the data presented; however; it must be interpreted cautiously. Repeat prostate biopsy with both systematic and targeted lesion biopsy should be performed based on this information.

Novel genomic tissue-based testing has been validated to provide independent predictive information, in addition to traditional clinical criteria, that can be used to guide treatment decisions. The Prolaris Cell Cycle Progression score (Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA) has been shown to predict PCa-specific mortality in a watchful waiting cohort of men with varying clinical risk [15]. The Oncotype DX gene expression assay (Genomic Health, Inc., Redwood City, CA, USA), more directed toward men with low-risk and low-volume intermediate-risk disease, has been validated to predict the likelihood of adverse pathology (defined as predominant Gleason 4 or T3a or lower disease) within the prostate based on biopsy tissue [15]. Both assays may aid clinical decision making depending on which outcomes patients and clinicians find particularly relevant. Other biomarkers have been studied in the AS setting including urinary PCA3 and TMPRSS:ERG fusions; however these were studied primarily in low-risk disease and have not correlated with disease progression over time [16].

3. Treatment strategy

The optimal management for this case involves a thorough discussion of the risks from this cancer (for his longevity) and the risks for his quality of life and functioning from treatment in light of his priorities and expectations. Novel technologies including tissue-based genomics and mpMRI can be used to augment risk assessment. Although the risks of disease progression with AS will be higher than for immediate radical treatment, they are low in absolute terms. AS could lead to better preservation of quality of life. This patient's treatment decisions must be individualized after well-informed discussions weighing his value in maintaining function against the risks of disease progression.

Conflicts of interest

Dr. Dall’Era is a speaker and research collaborator for Genomic Health, an advisory panel member for Astra Zeneca, and a speaker for MDx Health. Dr. Davies has nothing to disclose.

References

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Footnotes

a Department of Urology, University of California Davis, Davis Medical Center, Sacramento, CA, USA

b Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA

Corresponding author. Department of Urology, University of California Davis, Davis Medical Center, 4860 Y Street, Suite 3500, Sacramento, CA 95817, USA.

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