Active Surveillance in Prostate Cancer: Current and Potentially Emerging Biomarkers for Patient Selection Criteria

Abstract

<b><i>Background:</i></b> Prostate cancer (PCa) represents one of the most frequent malignancies and the fifth leading cause of cancer death in adult men worldwide. PCa mortality rates have been declining in several Western countries; one of the possible reasons may be related to the application of prostate-specific antigen early detection policies. These early detection protocols increase PCa-specific patient survival; however, a high percentage of these cases corresponds to low-risk PCa that grows very slowly and is unlikely to metastasize to threaten survival. Many low-risk PCa patients receive aggressive therapies, such as radical prostatectomy and radiotherapy, that are costly for patients and/or health systems and generate side effects that affect the quality of life. An alternative to surgery and radiotherapy treatments for low-risk PCa is active surveillance (AS), a strategy based on close disease monitoring and intervention only if the disease progresses. However, proper identification of low-risk PCa patients at the time of diagnosis is essential for the effectiveness AS. The selection of AS candidates remains challenging; thus, effective prognostic biomarkers are needed. <b><i>Summary:</i></b> This review article addresses the characteristics of the current and emerging PCa prognostic biomarkers, including tests available for tissue, blood, and urine analyses, for the appropriate selection of PCa patients for AS. In addition, and based on published literature, we performed a selection of potential new biomarkers that can distinguish low-risk PCa. <b><i>Key Messages:</i></b> The literature search yielded four tissue-based tests, two blood-based tests, and six urine-based tests that can be used to determine PCa risk classification. However, most available tests are expensive; thus, cost-effective analyses are needed in order to obtain the approval of government agencies and to be financed by the health systems. Available prognostic urine tests have shown great progress over the last years, and they have the advantage of being minimally invasive; therefore, they may become a routine disease progression test for patients under AS. In addition, new research conducted in the last decade has shown promising biomarkers, including mRNA, miRNA, long noncoding RNA, and metabolites, that could improve existing tests or allow the development of new tools for AS patient selection.

Comparison of Outcomes of Active Surveillance in Intermediate-Risk Versus Low-Risk Localised Prostate Cancer Patients: A Systematic Review and Meta-Analysis

“…Therefore, we can probably expect that the present difference between the two groups would be minimised in the modern AS series where patients have a routine upfront MRI scan followed by systematic and targeted biopsies, and where only low-volume GG 2 IRPC patients are included for AS [ 48 , 49 ]. In addition, use of novel biomarkers and molecular genetics [ 50 , 51 ] in assessing disease aggressiveness and selecting appropriate IRPC candidates for AS would further contribute to better oncological outcomes.…”

Prostate Cancer: Genetics, Epigenetics and the Need for Immunological Biomarkers

“…Early detection of PC improves overall patient survival in low-risk patients, but has no effect on the survival of patients with metastatic cancer [ 149 , 150 , 165 ]. Since the management strategy for low-risk patients is active monitoring, careful patient selection and accuracy in risk assessment require new, more precise and more specific biomarkers, since randomized controlled trials have shown that PSA screening has no effect on overall mortality or prostate cancer-caused mortality [ 166 ].…”

“…In the majority of patients, localized PC is multifocal, due to the fact that cancer most often occurs in the peripheral zone of the prostate, the surrounding pseudocapsule is involved in 80% of clinically detected cases of cancer [ 150 , 151 ]. In the following stages, the cancer cells invade the seminal vesicles and paraprostatic tissue, regarded by the international TNM classification as T3, or the urinary bladder, levator muscles, external sphincter and/or anterior abdominal wall, which is the T4 stage [ 151 ].…”

Can We Predict Prostate Cancer Metastasis Based on Biomarkers? Where Are We Now?

“…For localized low-and favorable intermediate-risk PC, currently, the best treatment options are radical prostatectomy, radiation therapy or AS. Biomarkers to define the best candidates for these treatments in AS are not addressed in the current review because they were reviewed in a previous work [19]. For unfavorable intermediate-and high-risk PC, current treatments include RP plus extended lymphadenec-tomy, radiotherapy plus ADT and possibly abiraterone for high-risk patients [76,82,84].…”

“…Different types of biomarkers have been studied in PC as tools for the analysis of the risk of progression, with the potential for application in the accurate identification of candidates for active surveillance (AS), adjuvant therapy and/or new therapy modalities. We recently published a review of the role of biomarkers in AS [19]. This review included urine, blood and tissue biomarkers.…”