IN A STATE-OF-THE-ART LECTURE, Chris Bangma, MD, PhD, Professor of Urology at Erasmus MC in Rotterdam, The Netherlands, discussed his findings as principal investigator for the Prostate Cancer Research International Active Surveillance (PRIAS) study and reviewed the effects and management of anxiety and depression that men with prostate cancer experience when they undergo AS.
AS has become a mainstay treatment option for men with low-risk prostate cancer, as defined by the guidelines of the American Urological Association (AUA) and European Association of Urology (EAU), Dr. Bangma acknowledged. It is a relatively recent phenomenon that emerged to address concerns about overdiagnosis and overtreatment of prostate cancer and the unacceptable side effects of definitive therapies. AS has changed the landscape of the management of the disease. Ten years ago, more than 90% of men with prostate cancer were treated radically, with surgery or radiation, Dr. Bangma noted.1 It is the treatment approach with low-risk prostate cancer in men whose age and general health make them candidates for radical local therapy. Patients are regularly monitored over time for progression of disease, and if so, are offered definitive treatment. Patients’ uncertainty and fear of prostate cancer progression, which a patient who decides to pursue AS must inevitably deal with, are not always discussed, Dr. Bangma acknowledged.
Dr Bangma recalled that in a study looking at the PRIAS follow-up protocol,2 the compliance rate for men with PSA visits was 91%, but the compliance for standard repeat biopsies declined over time (81%, 60%, 53%, and 33% for 1, 4, 7, and 10 years, after diagnosis respectively). This led to questions of whether prostate biopsies could be replaced by imaging or markers to avoid non-compliance and early drop-out, but also to questions about the psychological impact on these patients that leads to noncompliance.
Earlier research from the PRIAS study published in 2010 indicated that anxiety and uncertainty about treatment decisions were lower in AS compared with definitive therapy and that anxiety did not increase over time.3
To study the cross-section between anxiety and prostate cancer treatment decision, it is necessary to define and quantify what anxiety is and how it relates to quality of life, Dr. Bangma stressed. Anxiety exists on a broad spectrum and can be a normal stress response or, on the other extreme, pathologic. It directly affects patients’ quality of life. It can influence a patient’s decision to a specific treatment and can reduce treatment compliance or alternatively cause a patient to seek out unnecessary interventions, e.g., ~26% of patients with anxiety obtained extra medications. The PRIAS study found that around 10% of patients who decided on AS and subsequently underwent invasive treatment was due to patient and or physician anxiety, not progression of disease,4 which can influence outcome by leading to overtreatment. The reason for this can be multifactorial, Dr. Bangma said, involving fear of progression; losing curative options; painful disease and death; partner concerns; financial issues; and decisional conflict.
Various validated metrics (questionnaires) can be used to evaluate quality of life and anxiety, Dr. Bangma noted, including the EQ-5D-5L (generic health), EORTC-QLQ-30 (cancer-related quality of life), EPIC 26 (Expanded Prostate cancer Index Composite short form 26), and RAND-36 (health-related quality of life, including a domain on emotional wellbeing).
One of the “two most notorious controversies about anxiety and AS,” Dr. Bangma noted, are that although living with untreated prostate cancer leads to anxiety, it may be associated with lower levels of anxiety compared with curative treatment that leads to loss of physical function, and treatment. Also, diagnostic testing may cause stress in some patients, while decreasing stress in others. The types of studies that have address these questions fall into three broad categories, Dr. Bangma explained. These are:
- Cross-sectional snapshot studies: EUPROMS, a survey of prostate cancer patients, showed no difference in anxiety between patients who decided on AS and those who chose definitive therapy.5
- Longitudinal studies: A retrospective analysis of 302 patients on AS from the REDEEM (from the Reduction by Dutasteride of clinical progression Events in Expectant Management) study found that 5% had high level of anxiety that was not correlated with the time to treatment shift.6 Other studies in this category include ProtecT,7 HAROW,8 and Finnish PRIAS.9
- Psychological personality studies: The PRIAS study found that anxiety and fear of progression decreased significantly over time.10 Further, in subgroup analysis of patients from Japan, PRIAS showed better quality of life scores in the AS group,11 and in the Finnish PRIAS group only 3.5% of the men who discontinued AS within the first 3-6 months.8
Dr. Bangma pointed out that there have been no randomized trials and many of the studies on anxiety have focused on patients who chose conservative management, who are a self-selected cohort, which can limit its generalizability.
Dr. Bangma stressed the importance of understanding and appropriately identifying which patients may have a potential increase in anxiety secondary to choosing AS. Neuroticism and introversion are associated with increased risk for depression and anxiety, he cautioned, and symptoms of anxiety and depression are more frequent in individuals who live alone or have lower levels of education. It may also be possible to recognize coping mechanisms that patients may adopt to cope with anxiety, such as fighting spirit, avoidance, anxious preoccupation, helplessness, and fatalism, he added. Even a brief compassionate intervention can help reduce patient anxiety, he suggested. In addition, educating patients and enabling them to understand more about their disease process or referring them to an online support group can effectively reduce anxiety and depression. The presence of nurse navigators can help patients deal with the healthcare system.
Summarizing the main messages from his presentation, Dr. Bangma stressed the significant impact that anxiety places on decision making and outcome. Anxiety may influence 3.5-7% of prostate cancer patients to choose conservative management such as active surveillance over radical therapy. Care providers should identify patients with less education and those who live alone, as they may experience more distress. This emotional distress could be routinely assessed with validated instruments before clinical consultation. Finally, Dr. Bangma urged that “simple interventions and support currently available to provide coping mechanisms should be offered early on.”
David Ambinder, MD is a urology resident at New York Medical College / Westchester Medical Center. His interests include surgical education, GU oncology, and advancements in technology in urology. A significant portion of his research has been focused on litigation in urology.
- Klotz L. Active surveillance for low-risk prostate cancer. Curr Opin Urol. 2017;27(3):225-230. DOI: 10.1097/MOU.0000000000000393
- Bokhorst LP, Alberts AR, Rannikko A, et al. Compliance rates with the Prostate Cancer Research International Active Surveillance (PRIAS) protocol and disease reclassification in noncompliers. Eur Urol. 2015;68(5):814-821. DOI: 10.1016/j.eururo.2015.06.012
- van den Bergh RC, Essink-Bot ML, Roobol MJ, et al. Do anxiety and distress increase during active surveillance for low risk prostate cancer? J Urol. 2010;183 (5):1786- 1791. DOI: 10.1016/j.juro.2009.12.099
- Bokhorst LP, Valdagni R, Rannikko A, et al; PRIAS study group. A decade of active surveillance in the PRIAS study: an update and evaluation of the criteria used to recommend a switch to active treatment. Eur Urol. 2016;70(6):954-960. DOI: 10.1016/j. eururo.2016.06.007
- Venderbos LDF, Deschamps A, Dowling J, et al. Europa Uomo Patient Reported Outcome Study (EUPROMS): descriptive statistics of a prostate cancer survey from patients for patients. Eur Urol Focus. Published online December 3, 2020.DOI: 10.1016/j. euf.2020.11.002
- Naha U, Freedland SJ, Abern MR, Moreira DM. The association of cancer-specific anxiety with disease aggressiveness in men on active surveillance of prostate cancer. Prostate Cancer Prostatic Dis. 2021;24(2):335-340. DOI: 10.1038/s41391-020-00279-z
- Hamdy FC, Donovan JL, Lane JA, et al; ProtecT Study Group. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med.2016;375(15):1415-1424. DOI: 10.1056/NEJMoa1606220
- Herden J, Schwarte A, Werner T, Behrendt U, Heidenreich A, Weissbach L. Long-term outcomes of active surveillance for clinically localized prostate cancer in a community- based setting: results from a prospective non-interventional study, World J Urol. 2021;39(7):2515-2523. DOI: 10.1007/s00345-020-03471-x
- Lokman U, Vasarainen H, Lahdensuo K, et al. Prospective longitudinal health-related quality of life analysis of the Finnish Arm of the PRIAS active surveillance cohort: 11 years of follow-up. Eur Urol Focus. Published online July 6, 2021: DOI: 10.1016/j.euf.2021.06.008
- Venderbos LD, van den Bergh RC, Roobol MJ, et al. A longitudinal study on the impact of active surveillance for prostate cancer on anxiety and distress levels. Psychooncology. 2015;24(3):348-354. DOI: 10.1002/pon.3657
- Hirama H, Sugimoto M, Miyatake N, et al. Health-related quality of life in Japanese low- risk prostate cancer patients choosing active surveillance: 3-year follow-up from PRIAS- JAPAN. World J Urol. 2021;39(7):2491-2497. DOI: 10.1007/s00345-020-03494-4