The Probability of Remaining Under Active Surveillance for Localized Prostate Cancer

An Analysis of Young Patients in the Framework of the Multicenter ProjuMa Registry Study

Background: After a diagnosis of prostate cancer, the 15-year cancer-specific survival probability is high; in suitable patients, active surveillance lessens the side effects of curative treatment. Limited evidence is available on the continuation of active surveillance in young prostate cancer patients in Germany.

Methods: Using data that were reported, as required by law, to the population-based cancer registries of the German federal states of North Rhine–Westphalia, Baden–Württemberg, and Rhineland–Palatinate, we studied the course of 732 patients under 60 years of age who were under active surveillance after receiving a diagnosis of low-risk localized prostate cancer (ISUP grade 1 or 2) in the years 2016–2021.

Results: The median duration of follow-up was 28 months. 64% [61%; 68%] of the patients were still under active surveillance at two years; this was true for 66% [62%; 70%] of those with ISUP grade 1 disease, 46% [37%; 58%] of those with ISUP grade 2 disease, and 72% [63%; 83%] of those for whom no Gleason grading was available. 62% of discontinuations occurred without any documented progression and without a documented patient-initiated decision.

Conclusion: The two-year probability of young prostate cancer patients remaining under active surveillance was lower in Germany than in other countries. The cancer registries mostly received no information concerning the clinical rationale for the discontinuations. The potentially incomplete reporting of reasons for discontinuing active surveillance suggests that clinical reporting practices should be improved.

Cite this as: Claassen K, Justenhoven C, Hermann S, Brandhorst J, Lakes J, Werner D, Kajüter H, Karpinski M, Arndt V, Stang A, Albers P: The probability of remaining under active surveillance for localized prostate cancer: An analysis of young patients in the framework of the multicenter ProjuMa registry study. Dtsch Arztebl Int 2025; 122: 401–5. DOI: 10.3238/arztebl.m2025.0081

In 2022, approximately 66 000 men in Germany were newly diagnosed with prostate cancer, 40% of whom (26 400 men) had localized disease (1). Localized prostate cancer has not yet breached the prostate capsule and involves neither regional lymph node infiltration nor distant metastasis.

For patients with this stage of disease, the randomized ProtecT study reported an absolute cancer-specific survival probability of over 98% at 10 years and over 96% at 15 years (2, 3). There were no clinically relevant differences between active surveillance and the initial curative treatments of radical prostatectomy and radiotherapy, with the event of interest (death due to prostate cancer) occurring in only 45 patients (2.7%) within 15 years (2, 3). In a large retrospective study, Timilshina et al. presented administrative data from Ontario, Canada, showing a cancer-specific mortality rate that was, in relative terms, 66% higher under active surveillance compared to initial curative treatment (4). However, this was a non-randomized study and the cancer-specific 10-year survival probability, at 98% overall, was also very high.

According to the S3 guideline valid during the study period, the following criteria, consistent with the definition of a very low recurrence risk, were considered conditions for active surveillance: a PSA level of no more than 10 ng/mL, a Gleason score of 6 or less, stage T1 or T2a according to the TNM classification, evidence of carcinoma in no more than two cores, and maximum core involvement of 50% (5, 6). However, the distinction between low and very low risk is increasingly seen as obsolete, given that active surveillance should be considered in both cases (7). A Gleason score of up to 6 corresponds to grade group 1 according to the International Society of Urological Pathology (ISUP). A Gleason score of 7a (3 + 4), which is classified as a favorable intermediate risk, corresponds to ISUP grade group 2—here, active surveillance remains the subject of scientific debate (8, 9). The risks of active surveillance need to be weighed against the possible side effects of initial curative treatments. In the first 12 years, active surveillance in the ProtecT study showed fewer negative effects on urinary continence and sexual function compared to radical prostatectomy (10). Despite the fact that at 12 years, the differences evened out to some extent, active surveillance enabled patients to avoid—or at least delay—the side effects of radical interventions for longer (11). Although, according to more recent data, active surveillance can be equally recommended for young men (< 60 years), the evidence on active surveillance in this age group was for a long time limited (9, 12). One can assume that this limited evidence base had an effect not only on clinical decision-making but also on treatment adherence. No scientific analyses on the probability of remaining under active surveillance in Germany have been available as yet. This study is based on cancer registry data reflecting the reality of inpatient and outpatient healthcare. The aim was to describe the probability of remaining under active surveillance depending on ISUP grade group in young patients who initially fulfilled the inclusion criteria for active surveillance.

Methods

The analysis presented below was based on data from the population-based cancer registries of North Rhine–Westphalia (NRW), Baden–Württemberg (BW), and Rhineland–Palatinate (RP). As part of the research project “Prostatakarzinom des jungen Mannes” (ProjuMa; prostate cancer in young men), service providers were actively contacted to make them aware of the existing legal requirement of mandatory reporting and to request that missing data be retrospectively reported in order to counteract potential incompleteness in terms of treatment and follow-up reports.

Inclusion criteria at the time of diagnosis included—in addition to age over 14 and under 60 years as well as residency in Germany—a diagnosis of prostate cancer (C61 according to ICD-10) between 2016 and 2021 that was initially subject to active surveillance. Exclusion criteria included advanced T stage (T > 2), lymph node infiltration (N > 0), or distant metastasis (M > 0) according to the TNM classification. Patients in an ISUP grade group higher than 2 or with a PSA level of over 10.0 ng/mL were also excluded.

The event of discontinuation of active surveillance was either directly reported to the cancer registries or indirectly inferred from information contained in reports showing active treatment or disease progression:

• Prostate surgery (see the eTable for a list of the German operation and procedures codes [Operationen- und Prozedurenschlüssel, OPS])
• Radiotherapy of the prostate
• Systemic treatment for prostate cancer (for example, androgen deprivation therapy)
• Lymph node infiltration or distant metastasis
• Death of the patient due to C61 consistent with unicausal cause-of-death statistics.

eTable

Four-digit German operation and procedure codes (Operationen- und Prozedurenschlüssel, OPS) for surgical treatment measures from which discontinuation of active surveillance was inferred in patients with initially localized prostate cancer

When directly reporting a case of discontinuation, the information on whether the patient experienced disease progression or whether he decided against continuing active surveillance should also be provided, in line with the basic oncology dataset. If no information was provided in this regard, it was verified whether, in addition to the discontinuation of active surveillance, there had been any reports of upstaging (T > 2, N > 0, M > 0), upgrading (ISUP grade group > 2), or a rise in PSA level (> 10.0 ng/mL).

The endpoint was the 2-year probability of remaining under active surveillance, which was estimated using the Kaplan–Meier method up to the end of the respective mortality follow-up. Deaths due to causes other than C61, as well as reaching the last follow-up point in the study before discontinuation of active surveillance were documented, resulting in the end of the observation period (referred to as right-censoring). The analyses were also stratified according to ISUP grade group 1, 2, or unknown. Statistical analysis was performed using R software (2022.07.2 version) with the “survival” package. The 95% confidence intervals for the probability of remaining were estimated using Greenwood’s formula (13).

Results

According to the reported data, 9465 patients under the age of 60 years were diagnosed with localized prostate cancer in the abovementioned German federal states between 2016 and 2021. Of these, 42.1% were from NRW (3986 patients), 38.9% from BW (3684 patients), and 19% from RP (1795 patients). In total, 732 of these patients (7.7%) were registered as under active surveillance. For 344 of the 732 patients (47.0%), discontinuation of active surveillance was directly reported or could be inferred from other information contained in the reports. For illustrative purposes, Figure 1 presents a flow diagram showing the distribution of patients across the different endpoints following the start of active surveillance, together with the corresponding reason.

Figure 1

Flow diagram of the distribution of patients under 60 years of age diagnosed with localized prostate cancer between 2016 and 2021 in North Rhine–Westphalia, Baden–Württemberg, and Rhineland–Palatinate across the different endpoints after the start of active surveillance (including the corresponding reason)

The median duration of follow-up of the study cohort was 28 months. In only 27 patients (3.7%), follow-up already ended in the first year: In 26 patients, this was due to the fact that they had reached the last follow-up point of the study, and in one patient as a result of death due to a cause other than prostate cancer—in each case without documented discontinuation of active surveillance. For the 26 patients, the start of active surveillance was registered relatively close to the end of the follow-up phase. These patients were included since they contributed to the estimation of the probability of remaining in the first year (but not thereafter).

Baseline characteristics are presented in the Table. The distribution by place of residence at the time of diagnosis reflected the population size of the federal states represented. A largely uniform distribution of patients was observed with regard to age, T stage, and ISUP grade group, as well as across the years of diagnosis (2016–2021). Noticeable differences were seen in baseline PSA levels: These were on average higher in NRW at 5.5 (± 2.1) ng/mL compared to BW at 2.8 (± 3.2) ng/mL. PSA levels were not available for RP. Of the 11 patients (1.1 %) that died during follow-up, eight were from NRW (72.7%).

Table

Baseline characteristics by place of residence of the 732 actively surveilled patients under 60 years of age diagnosed with localized prostate cancer

At 24 months, an estimated 66.2% [95% confidence interval: 62.2; 70.4] of patients with ISUP grade group 1 disease were still under active surveillance (314 patients). This was true for 46.3% [37.3; 57.5] of patients with ISUP grade group 2 disease (43 patients) and for 72.3% [63.2; 82.6] of patients for whom no grading was available (56 patients). This resulted in a difference in the 2-year probability of remaining under active surveillance between ISUP grade groups 1 and 2 of 19.9% [14.1; 25.7]. Across ISUP grade groups, the overall 2-year probability of remaining under surveillance was 64.2% [60.7; 67.8]. The other group-specific probabilities of remaining up to 75 months following the start of active surveillance are shown in Figure 2.

Figure 2

Kaplan–Meier estimate of the probability of remaining under active surveillance for a maximum of 75 months among patients under 60 years of age diagnosed with localized prostate cancer between 2016 and 2021 in North Rhine–Westphalia, Baden–Württemberg, and Rhineland–Palatinate (stratified according to ISUP grade group)

The median duration for which patients remained under active surveillance was 56 months [45; 71] in ISUP grade group 1, 22 months [12; 37] in ISUP grade group 2, and 75 months [53; not available] for patients with unknown grading. For this latter group, there were too few events to reach an upper limit of the confidence interval for the median duration of remaining under surveillance. Overall, the median duration of remaining under active surveillance was 53 months [43; 63].

In 36.3% [31,2; 41,7] of cases, the cancer registries were informed about disease progression upon discontinuation of active surveillance, or this was inferred from a report on histological upgrading, TNM upstaging, or an elevated PSA level, meaning that the criteria for active surveillance were no longer met (125 patients). In 53.2% [47.8; 58.6] of cases, patients switched to active treatment (surgery, radiotherapy, or systemic treatment) without the cancer registries receiving information regarding progression or the patient’s decision not to continue active surveillance (183 patients). According to the reported information, 1.5% [0.5; 3.4] of patients decided against continuing the surveillance regime or wished to switch to active treatment (five patients). For 8.7% [6.0; 12.2] of discontinuations, no reason was provided to the cancer registries (30 patients). The remaining 0.3% [0.0; 1.6] of patients died of their prostate cancer (one patient), according to unicausal cause-of-death statistics. The situation is presented in visual form in Figure 3.

Figure 3

Waffle chart of the reasons for discontinuing active surveillance in 344 patients under 60 years of age diagnosed with localized prostate cancer between 2016 and 2021 in North Rhine–Westphalia, Baden–Württemberg, and Rhineland–Palatinate (in percent, rounded)

A subgroup analysis was conducted of patients in NRW in whom discontinuation of active surveillance was inferred from the reporting of active treatment without disease progression or a patient decision against continuing active surveillance. Of 93 patients in total, 74.2% received prostatectomy (69 patients) as primary treatment, according to the reported information. The NRW cancer registry received histological findings for 36.2% of these (25 patients). In none of these patients could progression beyond ISUP grade group 2 be seen.

Discussion

According to the reported information, only around 8% of patients under the age of 60 years with localized prostate cancer in NRW, BW, and RP were actively surveilled during the study period. However, since active surveillance treatment was less reliably documented or reported than were incident cases despite mandatory reporting, this proportion of actively surveilled patients may have been underestimated.

For comparison, the proportion of active surveillance in the treatment of low-risk prostate cancer patients, without age restrictions, was reported to be 60% in the US in 2021 and 69% in Canada in 2014 (14, 15). In contrast, less than a third of suitable patients in certified prostate cancer centers in Germany were actively surveilled in 2021 (16). In both the US study and in Germany, men with a PSA level below 10 ng/mL, ISUP grade group 1, and a T stage up to “T2a” were considered suitable candidates for active surveillance, thereby ensuring comparability. In the Canadian study, on the other hand, all men with ISUP grade group 1 prostate cancer were included.

In total, 64% of patients in the present study who were initially under active surveillance remained so for at least 2 years. This was true for 66% of patients with ISUP grade 1 and 46% of patients with ISUP grade 2 disease. Thus, the central contribution of this study is that it reports, for the first time, on the probability of remaining under active surveillance among young prostate cancer patients in Germany.

One can assume a high level of completeness here, since only those cases for which the start of active surveillance had already been reported were included. Moreover, reports confirming discontinuation of active surveillance were expected not only from the treating uro-oncologists who were actively contacted but also from surgeons, pathologists, and radiotherapists. Under the plausible assumption that a service provider’s reporting behavior (which is largely automated via interfaces to hospital and practice information systems) was not related to clinical outcomes, the reported cases permitted an unbiased estimate of the number of patients remaining under active surveillance.

International estimates ranged between an 80% probability of remaining under active surveillance at 2 years, 45% at 10 years (2), and 39% at 15 years (3) in the English ProtecT study (2), and 85% at 1 year, 58% at 3 years, and 52% at 5 years in Timilshina et al. (15). While 77% of patients in the ProtecT study (with a median age at diagnosis of 63 years) were classified as ISUP grade group 1, the Canadian study (with a median age at diagnosis of 64) was limited to patients with ISUP grade group 1 disease. In the Movember GAP3 cohort (Global Action Plan Prostate Cancer Active Surveillance Initiative), 77% of patients from 12 countries remained under active surveillance at 2 years (17). These patients had a median age of 65 years and also all had ISUP grade group 1 disease.

Thus, the probability of remaining under active surveillance in ISUP grade group 1 in the present ProjuMa study was lower than the probability reported in Canadian registry data, the randomized ProtecT study data, and based on data provided by the specialized GAP3 centers. This is possibly due to the lower age of the ProjuMa cohort, in which the median age was 57 years. The results of the population-based ProjuMa study were also most closely in agreement with the registry-based study results of Timilshina et al.

While the 2-year probability of remaining under active surveillance was around 20% higher in ISUP grade group 1 than in ISUP grade group 2, the highest probability was seen in the group for whom no ISUP grade group was available. It is recommended that further studies include a standardized evaluation of initial MRI findings when determining the indication for active surveillance. The available data are limited to T stage and histology.

In 52% of cases, a switch to active treatment took place without any information being reported on progression or a patient’s decision not to continue active surveillance. This was true for only 30% of discontinuations in the GAP3 consortium data (17). Thus, a relevant limitation of the present analysis of the reasons for discontinuing active surveillance was the incomplete reporting of follow-up data. It was not possible to clearly differentiate between whether discontinuation of active monitoring was not preceded by progression, or whether progression was simply not reported. For a more reliable evaluation of the reasons for discontinuation, more complete reporting by clinical service providers subject to mandatory reporting is necessary.

In summary, this study provides initial evidence that only a small proportion of suitable patients was under active surveillance in Germany between 2016 and 2021. Once initiated, active surveillance tended to be discontinued relatively early, possibly due to the uncertainty during the study period regarding active surveillance of young men with prostate cancer. The cancer registries mostly received no information concerning progression or patient wishes as reasons for discontinuing active surveillance.

Conflict of interest statement
The authors declare that no conflict of interest exists.

Manuscript submitted on 18 December 2024, revised version accepted
on 5 May 2025.

Translated from the original German by Christine Rye.

Corresponding author
PD Dr. rer. medic. Kevin Claaßen

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