Early outcomes of active surveillance for localized prostate cancer

OBJECTIVE: To describe the preliminary clinical outcomes of active surveillance (AS), a new strategy aiming to individualize the management of early prostate cancer by selecting only those men with significant cancers for curative therapy, and illustrate the contrast with a policy of watchful waiting (WW). PATIENTS AND METHODS: Eighty men with early prostate cancer began AS at the authors' institution between 1993 and 2002. Eligibility included histologically confirmed prostatic adenocarcinoma, fitness for radical treatment, clinical stage T1/T2, N0/X, M0/X, a prostate specific antigen (PSA) level of < or = 20 ng/mL, and a Gleason score of < or = 7. PSA was measured and a digital rectal examination conducted at 3-6 month intervals. The decision between continued monitoring or radical treatment was informed by the rate of rise of PSA, and was made according to the judgement of each patient and clinician. During the same period, 32 men with localized prostate cancer (any T stage, N0/X, M0/X, any PSA, Gleason score < or = 7) were managed by WW; hormonal treatment was indicated for symptomatic prostate cancer progression. The PSA doubling time (DT) was calculated using linear regression of ln(PSA) against time, using all pretreatment PSA values. RESULTS: At a median follow-up of 42 months, 64 (80%) of the 80 patients on AS remained under observation, 11 (14%) received radical treatment and five (6%) died from other causes. No patient developed evidence of metastatic disease, none started palliative hormone therapy, and there were no deaths from prostate cancer. Of the 11 patients who received radical treatment all remained biochemically controlled with no clinical evidence of recurrent disease. The median PSA DT while on AS was 12 years. Twenty (62%) of the 32 patients on WW remained on observation, eight (25%) received palliative hormonal therapy and four (12%) died, including one from prostate cancer. CONCLUSIONS: AS is feasible in selected men with early prostate cancer. The natural history of this disease often appears extremely indolent, and most men on AS will avoid radical treatment. There is a marked contrast between AS (with radical treatment for biochemical progression) and WW (with palliative treatment for symptomatic progression). Ongoing studies are seeking to optimize the AS protocol, and to compare the long-term outcomes with those of immediate radical treatment.     

Patient acceptance of active surveillance as a treatment option for low-risk prostate cancer

Study Type – Decision analysis (lacking sensitivity analysis) Level of Evidence 4 What’s known on the subject? and What does the study add? Active surveillance is a management strategy that offers patients the hope of avoiding the side effects associated with unnecessary treatment. This study identifies the resources required by men who choose to be on active surveillance to support them in their treatment decision.

OBJECTIVES

• ? To examine the decision‐making processes of men on active surveillance (AS).
• ? To identify the resources that men want to access to make, support and sustain them while on AS.

PATIENTS AND METHODS

• ? Three‐part survey developed for this study based on a qualitative study of 25 men on AS.
• ? Survey items explored: role men assumed with their physician in treatment decision‐making, factors influencing decision to go on AS, and resources required while on AS.
• ? Surveys mailed out to cross‐sectional sample of men on AS for less than 10 years.

RESULTS

• ? 27% of the 73 men reported assuming an active role in treatment decision‐making with their urologist, 41% a shared role and 32% a passive role.
• ? 82% of men reported being comfortable and 90% being satisfied with their decision to be on AS.
• ? 55% reported not being anxious about the cancer progressing while on AS.
• ? Urologist’s opinion, current age, and impact of treatment on urinary function were main factors influencing treatment decision.
• ? Information on future treatment options, non‐traditional treatments and diet considered most important resources.

CONCLUSIONS

• ? Results suggest that once men make a decision to go on AS, they are satisfied with their decision and few report being anxious about progression of cancer.
• ? Men are strongly influenced by the treating specialist in taking up AS.
• ? Additional information and psychological support resources are required for men on AS.

     

Analysis of expanded criteria to select candidates for active surveillance of low-risk prostate cancer

We aimed to analyze the value of each criterion for clinically insignificant prostate cancer (PCa) in the selection of men for active surveillance (AS) of low-risk PCa. We identified 532 men who were treated with radical prostatectomy from 2006 to 2013 who met 4 or all 5 of the criteria for clinically insignificant PCa (clinical stage ≤ T1, prostate specific antigen [PSA] density ≤ 0.15, biopsy Gleason score ≤ 6, number of positive biopsy cores ≤ 2, and no core with > 50% involvement) and analyzed their pathologic and biochemical outcomes. Patients who met all 5 criteria for clinically insignificant PCa were designated as group A (n = 172), and those who met 4 of 5 criteria were designated as group B (n = 360). The association of each criterion with adverse pathologic features was assessed via logistic regression analyses. Comparison of group A and B and also logistic regression analyses showed that PSA density > 0.15 ng ml⁻¹ and high (≥7) biopsy Gleason score were associated with adverse pathologic features. Higher (> T1c) clinical stage was not associated with any adverse pathologic features. Although ≤ 3 positive cores were not associated with any adverse pathology, ≥4 positive cores were associated with higher risk of extracapsular extension. Among potential candidates for AS, PSA density > 0.15 ng ml⁻¹ and biopsy Gleason score > 6 pose significantly higher risks of harboring more aggressive disease. The eligibility criteria for AS may be expanded to include men with clinical stage T2 tumor and 3 positive cores.     

Outcomes of men on active surveillance for low-risk prostate cancer at a safety-net hospital

Purpose

To characterize demographic, disease, and cancer outcomes of men on active surveillance (AS) at a safety-net hospital and characterize those who were lost to follow-up (LTFU).

Identification of men with low-risk biopsy-confirmed prostate cancer as candidates for active surveillance

Background

A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS.

Sexual function with localized prostate cancer: active surveillance vs radical therapy

Study Type – Outcomes (cohort sample) Level of Evidence 2b What's known on the subject? and What does the study add? The study compares the sexual function of men with low‐risk prostate cancer who chose active surveillance (expectant management) with similar men who received radiation therapy or radical prostatectomy. The first group appeared to be sexually active more frequently and had less erectile dysfunction. The study was non‐randomized. No other studies exist on the effect of active surveillance on sexual function vs other treatment methods.

OBJECTIVE

• ? To compare sexual function of men with localized prostate cancer (PCa) on active surveillance (AS) with similar patients who received radical therapy.

PATIENTS AND METHODS

• ? Two groups of men with screening‐detected localized PCa were compared. The first were men on AS within the prospective protocol‐based Prostate Cancer Research International: Active Surveillance study. The second were men participating in the European Randomized Study of Screening for Prostate Cancer study who had received radical prostatectomy (RP) or radiation therapy (RT).
• ? Questionnaires were completed at two different timepoints after diagnosis or treatment (6 and 12–18 months). These contained 10 items on sexual function, the mental and physical component summary from the Short‐Form 12‐item health survey, the Center for Epidemiologic Studies Depression scale depression measure and the State Trait Anxiety Inventory general anxiety measure.
• ? Sexual function was compared between groups, and determinants were analysed in multivariable analysis, adjusting for baseline differences.

RESULTS

• ? A total of 65–68% of men on AS, 35–36% of those who underwent RP, 36–37% of those who underwent RT and 36% of men in the RP and RT groups combined (combined Tx) were sexually active.
• ? A total of 20–30% of men in the AS group, 86–91% of men in the RP group, 56–60% of men in the RT group and 71–76% of men in the combined Tx group were sexually inactive as a result of erectile dysfunction.
• ? A total of 44–51% of men in the AS group, 96% of men in the RP group, 73–76% of men in the RT group and 84–85% of men in the combined Tx group who were sexually active had problems getting or keeping an erection.
• ? In multivariable analysis these differences were significant, except for AS vs RT.

CONCLUSIONS

• ? Men with localized PCa on AS were more often sexually active than similar men who received radical therapy, especially RP. If not sexually active, this was less often attributable to erectile dysfunction for those on AS. If sexually active, this was less often associated with problems getting or keeping an erection for those on AS.
• ? The study was non‐randomized; the latest advances in RP and RT might impact results.

     

Predictive models for worsening prognosis in potential candidates for active surveillance of presumed low-risk prostate cancer

Purpose  

Low-risk prostate cancer patients clinically eligible for active surveillance can also be managed surgically. We evaluated the pathologic outcomes for this cohort that was treated by radical prostatectomy and devised nomograms to predict patients at risk of upgrading and/or upstaging.     

The role of multiparametric MRI in active surveillance for low-risk prostate cancer: The ROMAS randomized controlled trial

BackgroundWe aim to evaluate the impact of multiparametric magnetic resonance imaging and fusion-target biopsy for early reclassification of patients with low-risk Prostate Cancer in a randomized trial.Materials and methodsBetween 2015 and 2018, patients diagnosed with Prostate Cancer after random biopsy fulfilling PRIAS criteria were enrolled and centrally randomized (1:1 ratio) to study group or control group. Patients randomized to study group underwent multiparametric magnetic resonance imaging at 3 months from enrollment: patients with positive findings (PIRADS-v2>2) underwent fusion-target biopsy; patients with negative multiparametric magnetic resonance imaging or confirmed ISUP - Grade Group 1 at fusion-target biopsy were managed according to PRIAS schedule and 12-core random biopsy was performed at 12 months. Patients in control group underwent PRIAS protocol, including a confirmatory 12-core random biopsy at 12 months. Primary endpoint was a reduction of reclassification rate at 12-month random biopsy in study group at least 20% less than controls. Reclassification was defined as biopsy ISUP Grade Group 1 in >2 biopsy cores or disease upgrading.ResultsA total of 124 patients were randomized to study group (n = 62) or control group (n = 62). Around 21 of 62 patients (34%) in study group had a positive multiparametric magnetic resonance imaging, and underwent fusion-target biopsy, with 11 (17.7%) reclassifications. Considering the intention-to-treat population, reclassification rate at 12-month random biopsy was 6.5% for study group and 29% for control group, respectively (P < 0.001).ConclusionsThe early employment of multiparametric magnetic resonance imaging for active surveillance patients enrolled after random biopsy consents to significantly reduce reclassifications at 12-month random biopsy.     

Validating the total cancer location density metric for stratifying patients with low-risk localized prostate cancer at higher risk of grade group reclassification while on active surveillance

PurposeTo validate a previously proposed prognostic metric, Total Cancer Location (TCLo) density, in a contemporary cohort of men with grade group (GG) 1 prostate cancer (PCa) on active surveillance (AS).MethodsWe evaluated 123 patients who entered AS with maximum GG1 PCa at diagnostic and/or confirmatory biopsy. TCLo was defined as the total number of PCa locations identified on both biopsy sessions. TCLo density was calculated as TCLo / prostate volume [ml]. Primary endpoint was progression-free survival (PFS), defined as time from confirmatory biopsy to grade group reclassification (GGR) on repeat biopsy or prostatectomy. Optimal cut-point for TCLo density was predefined in a previously reported cohort and applied to this contemporary cohort. Kaplan-Meier and multivariable Cox regression analysis were used to estimate the association of predictors with PFS.ResultsDuring median follow-up of 7.8 years, (IQR 7.3–8.2) 34 men had GGR. Using previously defined cut-points, PFS at 5-years was 60% (95% CI: 44%–81%) vs. 89% (95% CI: 83%–96%) in men with high (≥0.06 ml^?1) vs. low (<0.06 ml^?1) TCLo density, and 63% (95% CI: 48%–82%) vs. 90% (95% CI: 83%–96%) in men with high (≥3) vs. low (≤2) TCLo (log-rank test: P < 0.0001, respectively). Adjusting for age, prostate volume, percent of positive cores and PSA, both higher TCLo density (HR [per 0.01 ml^?1 increase]: 1.18, 95% CI: 1.05–1.33, P = 0.005) and TCLo (HR: 1.69, 95% CI: 1.20–2.38, P = 0.002) were associated with shorter PFS.ConclusionThe previously suggested prognostic value of TCLo density was confirmed in this validation cohort. TCLo alone performed similarly well. Patients with high TCLo density (≥0.06 ml^?1) or TCLo (>2) were at greater risk of GGR while on AS. With external validation, these metric may help guide risk-adapted surveillance protocols.