Medium-term Outcomes of Active Surveillance for Localised Prostate Cancer

doi:10.1016/j.eururo.2013.02.020

European Urology

Volume 64, Issue 6, December 2013, Pages 981-987

https://doi.org/10.1016/j.eururo.2013.02.020 Get rights and content

Abstract

Background

Active surveillance (AS) aims to allow men with favourable-risk, localised prostate cancer to avoid unnecessary treatment.

Objective

To describe the clinical outcomes of a prospective study of AS.

Design, setting, and participants

A single-centre, prospective cohort study. Eligibility criteria included histologically proven prostate adenocarcinoma, age 50–80 yr, stage T1/T2, prostate-specific antigen level (PSA) <15 ng/ml, Gleason score (GS) ≤3 + 3 (GS ≤3 + 4 if aged >65 yr), and percent positive biopsy cores (PPC) ≤50%.

Intervention

Patients were assessed by serum PSA level, and digital rectal examination at 3-mo intervals in year 1, 4-mo intervals in year 2, and at 6-mo intervals thereafter. Transrectal ultrasound-guided prostate biopsy was performed after 18–24 mo and every 2 yr thereafter. Treatment was recommended for PSA velocity (PSAV) >1 ng/ml per year or adverse histology, defined as GS ≥4 + 3 or PPC >50%.

Outcome measurements and statistical analysis

Outcomes described, using Kaplan-Meier methods, were rate of adverse histology on repeat biopsy, freedom from treatment, biochemical control after deferred treatment, and overall survival. Analyses using Cox regression were performed to determine predictors of deferred treatment and adverse histology.

Results and limitations

The study enrolled 471 eligible patients from 2002 to 2011. Median age was 66 yr and median initial PSA value was 6.4 ng/ml. Eighty-eight percent of patients had T1 disease and 93% had GS ≤3 + 3. At median follow-up of 5.7 yr, the 5-yr rate of adverse histology and treatment-free probability was 22% (95% confidence interval [CI], 16–29%) and 70% (95% CI, 65–75%), respectively. There were two deaths from prostate cancer. Predictors of time to adverse histology were GS 7, PSAV >1 ng/ml per year, low ratio of free PSA to total PSA, and PPC >25%. Longer follow-up is needed to confirm the safety of this strategy.

Conclusions

This study demonstrates satisfactory medium-term outcomes for AS in selected men with localised prostate cancer.

Introduction

The challenge of localised prostate cancer (PCa) is to distinguish patients with significant cancers who will benefit from radical treatment, from the remainder who will not need any intervention in their lifetime. Active surveillance (AS) is a strategy of close observation with delayed curative treatment in the event of disease progression. It aims to avoid the unnecessary treatment of men with harmless PCa, but with timely radical treatment for those who need it. AS has become a standard approach. Data from the British Association of Urological Surgeons database indicate that as many as 40% of UK men with low-risk PCa elect AS [1].

There are no completed, randomised clinical trials comparing AS versus immediate treatment. There are, however, several prospective cohort studies that have reported short- and medium-term outcomes [2], [3], [4], [5], [6], [7], [8], [9], [10]. These studies have demonstrated the feasibility of AS and have indicated that most men on AS will avoid the need for radical treatment. However, there are limited data available on longer-term outcomes. This is an important limitation, because it is only with long-term follow-up that we will be able to assess the safety of an AS policy.

We previously reported the early outcomes of a prospective cohort study of AS at the Royal Marsden National Health Service Foundation Trust [11]. We now present updated data from this study.

Section snippets

Patients and methods

Eligibility was restricted to men aged 50–80 yr, with histologically proven prostate adenocarcinoma, clinical stage T1/T2, prostate-specific antigen (PSA) level <15 ng/ml, Gleason score (GS) ≤3 + 3 (GS 3 + 4 was permitted in patients aged >65 yr), and percentage of positive cores (PPC) ≤50% of the total number of biopsy cores. Extent of single-core involvement was not an eligibility criterion. Patients were diagnosed in a number of centres with a range of different biopsy techniques, reflecting

Results

Between March 2002 and May 2011, 499 patients with localised PCa were enrolled; 28 patients were ineligible, leaving 471 for analysis. Reasons for ineligibility are listed in Figure 1. The characteristics of eligible patients at consent are shown in Table 1. Median age was 66 yr and median initial PSA value was 6.4 ng/ml. Eight men on surveillance were lost to follow-up.

At a median follow-up of 5.7 yr, 412 men (87%) had undergone at least one repeat prostate biopsy. In total, 768 repeat

Discussion

This prospective study of AS of localised PCa has demonstrated encouraging clinical outcomes. In a selected population of men with localised PCa, 70% avoided treatment within 5 yr of diagnosis. The outcome of deferred treatment appears comparable to that of immediate treatment [13], [14] and the risk for death from PCa within the time frame of the study is very low. This is unsurprising given the favourable outcomes of watchful waiting reported in the Prostate Cancer Intervention versus

Conclusions

AS is an attractive management option for men with favourable-risk localised PCa. Most will avoid radical treatment, with a very low risk for death from PCa in the medium term.

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Cited by (189)

Active surveillance of low-grade prostate cancer using the SurACaP Criteria: A multi-institutional series with a median follow-up of 10 years
2024, French Journal of Urology
To report on the oncological outcomes of active surveillance (AS) in low-grade prostate cancer (PCa) patients using the French SurACaP protocol, with a focus on long-term outcomes.
This multicenter study recruited patients with low-grade PCa between 2007 and 2013 in four referral centers in France. The cohort included patients meeting the SurACaP inclusion criteria, i.e., aged ≤ 75 years, with low-grade PCa (i.e., ISUP 1), clinical stage T1c/T2a, PSA ≤ 10 ng/mL and ≤ 3 positive cores and tumor length ≤ 3 mm per core. The SurACaP protocol included a digital rectal examination every six months, PSA level measurement every three months for the first two years after inclusion and twice a year thereafter, a confirmatory biopsy in the first year after inclusion, and then follow-up biopsy every two years or if disease progression was suspected. Multiparametric magnetic resonance imaging (mpMRI) was progressively included over the study period.
A total of 86 consecutive patients were included, with a median follow-up of 10.6 years. Only one patient developed metastases and died of PCa. The estimated rates of grade reclassification and treatment-free survival at 15 years were 53.4% and 21.2%, respectively. A negative mpMRI at baseline and a negative confirmatory biopsy were significantly associated with a lower risk of disease progression (P < 0.05).
AS using the French SurACaP protocol is a safe and valuable strategy for patients with low-risk PCa, with excellent oncological outcomes after more than 10 years’ follow-up. Future studies are crucial to broaden the inclusion criteria and develop a personalized, risk based AS protocol with the aim of de-escalating follow-up examinations.
Grade 4.
Rapporter les résultats oncologiques de la surveillance active (SA) chez les patients atteints d’un cancer de la prostate (CaP) de bas grade selon le protocole français SurACaP, en mettant l’accent sur les résultats à long terme.
Cette étude multicentrique a recruté des patients atteints de CaP de bas grade entre 2007 et 2013 dans quatre centres de référence en France. La cohorte comprenait des patients répondant aux critères d’inclusion de SurACaP, c’est-à-dire âgés de moins de 75 ans, présentant un CaP de bas grade (ISUP 1), un stade clinique T1c/T2a, un taux de PSA ≤ 10 ng/mL et ≤ 3 carottes positives et une longueur tumorale ≤ 3 mm par carotte. Le protocole SurACaP comprenait un toucher rectal tous les six mois, une mesure du taux de PSA tous les trois mois pendant les deux premières années suivant l’inclusion et deux fois par an par la suite, une biopsie de confirmation la première année après l’inclusion, puis une biopsie de suivi tous les deux ans ou en cas de suspicion de progression de la maladie. L’imagerie par résonance magnétique multiparamétrique (IRMmp) a été progressivement incluse au cours de la période d’étude.
Au total, 86 patients consécutifs ont été inclus, avec un suivi médian de 10,6 ans. Un seul patient a développé des métastases et est décédé du CaP. Les taux estimés de reclassification du grade et de survie sans traitement à 15 ans étaient respectivement de 53,4% et de 21,2%. Une IRMmp négative initiale et une biopsie de confirmation négative étaient significativement associées à un risque plus faible de progression de la maladie (p < 0,05).
La SA selon le protocole français SurACaP est une stratégie sûre et utile pour les patients atteints de CaP à faible risque, avec d’excellents résultats oncologiques après plus de 10 ans de suivi. De futures études sont cruciales pour élargir les critères d’inclusion et développer un protocole de SA personnalisé, basé sur le risque, dans le but de désintensifier les examens de suivi.
Grade 4.
Active Surveillance for Prostate Cancer: Expanding the Role of MR Imaging and the Use of PRECISE Criteria
2024, Radiologic Clinics of North America
Patterns of multispecialty care for low- and intermediate-risk prostate cancer in the use of active surveillance
2023, Urologic Oncology: Seminars and Original Investigations
Multidisciplinary models of care have been advocated for prostate cancer (PC) to promote shared decision-making and facilitate quality care. Yet, how this model applies to low-risk disease where the preferred management is expectant remains unclear. Accordingly, we examined recent practice patterns in specialty visits for low/intermediate-risk PC and resultant use of active surveillance (AS).
Using SEER-Medicare, we ascertained whether patients saw urology and radiation oncology (i.e., multispecialty care) versus urology alone, based on self-designated specialty codes, for newly diagnosed PC from 2010 to 2017. We also examined the association with AS, defined as the absence of treatment within 12 months of diagnosis. Time trends were analyzed using Cochran-Armitage test. Chi-squared and logistic regression analyses were applied to compare sociodemographic and clinicopathologic characteristics between these models of care.
The proportion of patients seeing both specialists was 35.5% and 46.5% for low- and intermediate-risk patients respectively. Trend analysis showed a decline in multispecialty care in low-risk patients (44.1% to 25.3% years 2010–2017; P < 0.001). Between 2010 and 2017, the use of AS increased 40.9% to 68.6% (P < 0.001) and 13.1% to 24.6% (P < 0.001) for patients seeing urology and those seeing both specialists respectively. Age, urban residence, higher education, SEER region, co-morbidities, frailty, Gleason score, predicted receipt of multispecialty care (all P < 0.02).
Uptake of AS among men with low-risk PC has occurred primarily under the purview of urologists. While selection is certainly at play, these data suggest that multispecialty care may not be required to promote the utilization of AS for men with low-risk PC.
Targeted Multiparametric Magnetic Resonance Imaging/Ultrasound Fusion Biopsy for Quantitative Gleason 4 Grading Prediction in Radical Prostatectomy Specimens: Implications for Active Surveillance Candidate Selection
2023, European Urology Focus
Quantitative Gleason grading appears to be a reliable prognostic parameter and provides broader risk stratification then the traditional Gleason grading in patients with prostate cancer (PCa) treated with radical prostatectomy (RP).
To determine if quantification of Gleason pattern (GP) 4 for targeted and systematic biopsy (TBx + SBx) cores together with further clinical variables can identify the lowest quantitative GP 4 fraction on RP.
A total of 548 patients underwent TBx + SBx of the prostate and then RP, with pathology revealing Gleason score 3 + 4, 4 + 3, or 4 + 4 disease.
TBx + SBx of the prostate followed by RP.
GP 4 fraction thresholds of ≤5%, ≤10%, ≤15%, ≤20%, and ≤25% were compared between the TBx + SBx and RP specimens. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy for predicting the GP 4 fraction in the RP specimen were determined. Logistic regression models were used to establish a probabilistic relationship between various combinations of clinical and biopsy variables and the GP 4 fraction in the RP specimen.
GP 4 fractions of ≤5%, ≤10%, ≤15%, ≤20%, and ≤25% was observed in 33%, 49%, 58%, 65%, and 70% of patients on TBx, and 18%, 41%, 53%, 63%, and 70% of patients on RP, respectively. The sensitivity, specificity, NPV, PPV, and accuracy were 75%, 67%, 91%, 39%, and 74% for a TBx GP 4 fraction of ≤5%, and 65%, 85%, 65%, 85%, and 79% for a TBx GP 4 fraction of ≤25%, respectively. A model combining quantified TBx + SBx GP 4 with clinical parameters demonstrated the highest diagnostic accuracy. Limitations include the retrospective study design.
Our results demonstrate that the combination of MRI-TBx + SBx and GP 4 quantification allowed precise detection of a low fraction of GP 4 when using RP specimens as the reference standard. Moreover, we found that clinical variables including Prostate Imaging-Reporting and Data System score without biopsy are limited in detection of low GP 4 fractions.
Combination of targeted biopsy alone as well as combined with systematic biopsy and quantitative Gleason grading of biopsy specimen showed high agreement with pathology findings after surgical removal of the prostate. This could help in identifying patients who are suitable for active surveillance.
Modern Active Surveillance in Prostate Cancer: A Narrative Review
2023, Clinical Genitourinary Cancer
Citation Excerpt :
While most cohorts limit men with a serum PSA <10ng/mL, some tolerate higher levels; 1 <15ng/mL, 2 <20ng/mL, and 1 allowed any PSA. Most cohorts are limited to men with ISUP 1 prostate cancer, while 6 cohorts include men with ISUP 2 disease.5,14,17-19 Appropriate patient selection is essential for maximizing the benefits for AS, while avoiding the adverse effects of disease progression.
The use of PSA screening has led to downstaging and downgrading of prostate cancer at diagnosis, increasing detection of indolent disease. Active surveillance aims to reduce over-treatment by delaying or avoiding radical treatment and its associated morbidity. However, there is not a consensus on the selection criteria and monitoring schedules that should be used. This article aims to summarize the evidence supporting the safety of active surveillance, the current selection criteria recommended and in use, the incidence of active surveillance, barriers existing to its uptake and future developments in patient selection.
French AFU Cancer Committee Guidelines - Update 2022-2024: prostate cancer - Diagnosis and management of localised disease
2022, Progres en Urologie
The objective of the French Urology Association Cancer Committee is to propose an update of the recommendations for the diagnosis and management of prostate cancer (PC).
A systematic review of the literature from 2020 to 2022 was conducted by the CCAFU on the diagnosis and therapeutic management of localised PC, while evaluating the references and their levels of evidence.
The recommendations specify the genetics, epidemiology and means of diagnosing prostate cancer, as well as the notions of screening and early detection. MRI, the gold standard imaging examination for localised cancer, is recommended before prostate biopsies are performed. The transperineal approach reduces the risks of infection. The therapeutic methods are described and recommended according to the clinical context. Active surveillance is the gold standard of treatment for tumours with a low risk for progression. Early salvage radiotherapy is recommended in case of biochemical recurrence after radical prostatectomy. Imaging, particularly molecular imaging, helps to guide the decision-making in the event of biochemical recurrence after local treatment, but should not delay early salvage radiotherapy in the event of biological recurrence after radical prostatectomy.
This update of the French recommendations should help to improve the management of patients with PC.
Le but du Comité de Cancérologie de l’Association française d’urologie est de proposer une mise à jour des recommandations dans le diagnostic et la prise en charge du cancer de la prostate (CaP).
Une revue systématique de la littérature de 2020 à 2022 a été conduite par le CCAFU concernant les éléments de diagnostic et de prise en charge thérapeutique du CaP localisé, en évaluant les références avec leur niveau de preuve.
Les recommandations précisent la génétique, l’épidémiologie et les moyens diagnostiques du cancer de la prostate, les notions de dépistage et de détection précoce. L’IRM, examen d’imagerie de référence du cancer localisé, est recommandée avant la réalisation de biopsies prostatiques. La voie transpérinéale permet de réduire les risques infectieux. Les moyens thérapeutiques sont détaillés, et recommandés en fonction des situations cliniques. La surveillance active est le traitement de référence pour les tumeurs de faible risque évolutif. La radiothérapie de rattrapage précoce est recommandée en cas de récidive biologique post-prostatectomie totale. L’imagerie, notamment moléculaire, permet d’orienter la prise de décision en cas de récidive biologique après traitement local, mais ne doit pas retarder la radiothérapie de rattrapage précoce en cas de récidive biologique post-prostatectomie totale.
Cette actualisation des recommandations françaises doit contribuer à améliorer la prise en charge des patients porteurs d’un CaP.

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Prostate CancerMedium-term Outcomes of Active Surveillance for Localised Prostate Cancer

Abstract

Background

Objective

Design, setting, and participants

Intervention

Outcome measurements and statistical analysis

Results and limitations

Conclusions

Introduction

Section snippets

Patients and methods

Results

Discussion

Conclusions

Eur Urol

Eur Urol

Eur Urol

J Urol

Eur Urol

Eur Urol

Int J Rad Oncol Biol Phys

Eur Urol

J Urol

J Urol

Eur Urol

Urology

J Urol

Prostate Cancer
Medium-term Outcomes of Active Surveillance for Localised Prostate Cancer