Long-term and pathological outcomes of low- and intermediate-risk prostate cancer after radical prostatectomy: implications for active surveillance

Purpose!#!The safety of active surveillance (AS) in favorable intermediate-risk (FIR) prostate cancer (PCa) remains uncertain. To provide guidance on clinical decision-making, we examined long-term and pathological outcomes of low-risk and intermediate-risk PCa patients after radical prostatectomy (RP).!##!Methods!#!The study involved 5693 patients diagnosed between 1994 and 2019 with low-risk, FIR, and unfavorable intermediate-risk (UIR) PCa (stratification according to the AUA guidelines) who underwent RP. Pathological outcomes were compared, and Kaplan-Meier analysis determined biochemical recurrence-free survival (BRFS) and cancer-specific survival (CSS) at 5, 10, 15, and 20 years. Multiple Cox regression was used to simultaneously control for relevant confounders.!##!Results!#!Those at FIR had higher rates of upgrading and upstaging (12.8% vs. 7.2%, p < 0.001; 19.8% vs. 12.0%, p < 0.001) as well as pathological tumor and node stage (≥ pT3a: 18.8% vs. 11.6%, p < 0.001; pN1: 2.7% vs. 0.8%, p > 0.001) compared to patients at low risk. The 20-year BRFS was 69%, 65%, and 44% and the 20-year CSS was 98%, 95%, and 89% in low-risk, FIR, and UIR patients. On multiple Cox regression, FIR was not associated with a worse BRFS (HR 1.07, CI 0.87-1.32), UIR was associated with a worse BRFS (HR 1.49, CI 1.20-1.85).!##!Conclusion!#!Patients at FIR had only slightly worse pathological and long-term outcomes compared to patients at low risk, whereas the difference compared to patients at UIR was large. This emphasizes AS in these patients as a possible treatment strategy in well-counseled patients

No detrimental effect of a positive family history on postoperative upgrading and upstaging in men with low risk and favourable intermediate-risk prostate cancer: implications for active surveillance

Purpose!#!To assess whether a first-degree family history or a fatal family history of prostate cancer (PCa) are associated with postoperative upgrading and upstaging among men with low risk and favourable intermediate-risk (FIR) PCa and to provide guidance on clinical decision making for active surveillance (AS) in this patient population.!##!Methods!#!Participants in the German Familial Prostate Cancer database diagnosed from 1994 to 2019 with (1) low risk (clinical T1c-T2a, biopsy Gleason Grade Group (GGG) 1, PSA < 10 ng/ml), (2) Gleason 6 FIR (clinical T1c-T2a, GGG 1, PSA 10-20 ng/ml), and (3) Gleason 3 + 4 FIR (clinical T1c-T2a, GGG 2, PSA < 10 ng/ml) PCa who were subsequently treated with radical prostatectomy (RP) were analysed for upgrading, defined as postoperative GGG 3 tumour or upstaging, defined as pT3-pT4 or pN1 disease at RP. Logistic regression analysis was used to assess whether PCa family history was associated with postoperative upgrading or upstaging.!##!Results!#!Among 4091 men who underwent RP, mean age at surgery was 64.4 (SD 6.7) years, 24.7% reported a family history, and 3.4% a fatal family history. Neither family history nor fatal family history were associated with upgrading or upstaging at low risk, Gleason 6 FIR, and Gleason 3 + 4 FIR PCa patients.!##!Conclusion!#!Results from the current study indicated no detrimental effect of family history on postoperative upgrading or upstaging. Therefore, a positive family history or fatal family history of PCa in FIR PCa patients should not be a reason to refrain from AS in men otherwise suitable

Diversity of cancer-related identities in long-term prostate cancer survivors after radical prostatectomy

BACKGROUND: Individuals affected by cancer need to integrate this experience into their personal biography as their life continues after primary therapy, leading to substantial changes in self-perception. This study identified factors uniquely associated with 5 different cancer-related identities in order to improve the understanding of how self-perception in men affected by prostate cancer is associated with certain clinical and psychosocial characteristics. METHODS: In this cross-sectional study, long-term prostate cancer survivors after radical prostatectomy were asked to choose one of 5 cancer-related identities that described them best. Associations with sociodemographic, clinical, and psychological variables were investigated using multivariable logistic regression. RESULTS: Three thousand three hundred forty-seven men (mean age 78.1 years) surveyed on average 15.6 years after prostatectomy were included. Most men favored the terms “someone who has had cancer” (43.9%) which was associated with a mild disease course, and “patient” (26.3%) which was associated with ongoing therapy and biochemical disease recurrence. The self-descriptions “cancer survivor” (16.8%), “cancer conqueror” (10.9%) and “victim” (2.1%) were less common. “Cancer survivor” was associated with high perceived disease severity (OR: 1.86 [1.44–2.40]). “Cancer survivor” and “cancer conqueror” were related to high benefit finding (OR: 1.89 [1.48–2.40], OR: 1.46 [1.12–1.89] respectively), and only “cancer conqueror” was associated with high well-being (OR: 1.84 [1.35–2.50]). Identification as “victim” was associated with a positive depression screening and low well-being (OR: 2.22 [1.15–4.31], OR: 0.38 [0.20–0.72] respectively) (all p < 0.05). CONCLUSIONS: Although long-term survival is common among men affected by PCa, they display a large diversity in cancer-related identities, which are associated with unique clinical and psychological characteristics. These cancer-related identities and their distinctive properties are associated with psychological well-being even after a long follow-up

Accommodating heterogeneous missing data patterns for prostate cancer risk prediction

Objective: We compared six commonly used logistic regression methods for accommodating missing risk factor data from multiple heterogeneous cohorts, in which some cohorts do not collect some risk factors at all, and developed an online risk prediction tool that accommodates missing risk factors from the end-user. Study Design and Setting: Ten North American and European cohorts from the Prostate Biopsy Collaborative Group (PBCG) were used for fitting a risk prediction tool for clinically significant prostate cancer, defined as Gleason grade group greater or equal 2 on standard TRUS prostate biopsy. One large European PBCG cohort was withheld for external validation, where calibration-in-the-large (CIL), calibration curves, and area-underneath-the-receiver-operating characteristic curve (AUC) were evaluated. Ten-fold leave-one-cohort-internal validation further validated the optimal missing data approach. Results: Among 12,703 biopsies from 10 training cohorts, 3,597 (28%) had clinically significant prostate cancer, compared to 1,757 of 5,540 (32%) in the external validation cohort. In external validation, the available cases method that pooled individual patient data containing all risk factors input by an end-user had best CIL, under-predicting risks as percentages by 2.9% on average, and obtained an AUC of 75.7%. Imputation had the worst CIL (-13.3%). The available cases method was further validated as optimal in internal cross-validation and thus used for development of an online risk tool. For end-users of the risk tool, two risk factors were mandatory: serum prostate-specific antigen (PSA) and age, and ten were optional: digital rectal exam, prostate volume, prior negative biopsy, 5-alpha-reductase-inhibitor use, prior PSA screen, African ancestry, Hispanic ethnicity, first-degree prostate-, breast-, and second-degree prostate-cancer family history

The role of fatal family history and mode of inheritance in prostate cancer for long-term outcomes following radical prostatectomy

Purpose!#!To determine whether fatal family history (FFH) or mode of inheritance in prostate cancer (PCa) has an impact on long-term outcomes following radical prostatectomy (RP).!##!Methods!#!1076 PCa patients after RP with at least one deceased first-degree relative with PCa were included and stratified by FFH (four subgroups: fraternal, paternal, multiple, and none) and by mode of inheritance (two subgroups: male to male, non-male to male). We compared clinicopathological characteristics between subgroups with Fisher's exact or Chi-square tests. Biochemical recurrence-free survival (BRFS) and cancer-specific survival (CSS) were analyzed using the method of Kaplan and Meier. Simple and multiple Cox regression with backward elimination were performed to select prognostic factors for BRFS and CSS.!##!Results!#!Median age at surgery was 63.3 (range 35.9-79.4) years. The overall Kaplan-Meier estimated BRFS rate at 10 and 15 years was 65.6% and 57.0%, respectively. The overall Kaplan-Meier estimated CSS rate at 10 and 15 years was 98.1% and 95.7%, respectively. Neither FFH nor mode of inheritance were factors associated with worse BRFS. However, in multiple Cox regression, paternal FFH was an important prognostic factor for a better CSS (HR 0.19, CI 0.05-0.71, p = 0.014) compared to non-FFH.!##!Conclusion!#!FFH and mode of inheritance do not seem to be prognostic factors of worse long-term outcomes following RP. Rather, a paternal FFH was associated with a better CSS; however, the reasons remain unclear. Nevertheless, patients after RP and FFH could be reassured that their own PCa diagnosis is not associated with a worse long-term outcome

The role of fatal family history and mode of inheritance in prostate cancer for long-term outcomes following radical prostatectomy

Abstract Purpose To determine whether fatal family history (FFH) or mode of inheritance in prostate cancer (PCa) has an impact on long-term outcomes following radical prostatectomy (RP). Methods 1076 PCa patients after RP with at least one deceased first-degree relative with PCa were included and stratified by FFH (four subgroups: fraternal, paternal, multiple, and none) and by mode of inheritance (two subgroups: male to male, non-male to male). We compared clinicopathological characteristics between subgroups with Fisher’s exact or Chi-square tests. Biochemical recurrence-free survival (BRFS) and cancer-specific survival (CSS) were analyzed using the method of Kaplan and Meier. Simple and multiple Cox regression with backward elimination were performed to select prognostic factors for BRFS and CSS. Results Median age at surgery was 63.3 (range 35.9–79.4) years. The overall Kaplan–Meier estimated BRFS rate at 10 and 15 years was 65.6% and 57.0%, respectively. The overall Kaplan–Meier estimated CSS rate at 10 and 15 years was 98.1% and 95.7%, respectively. Neither FFH nor mode of inheritance were factors associated with worse BRFS. However, in multiple Cox regression, paternal FFH was an important prognostic factor for a better CSS (HR 0.19, CI 0.05–0.71, p = 0.014) compared to non-FFH. Conclusion FFH and mode of inheritance do not seem to be prognostic factors of worse long-term outcomes following RP. Rather, a paternal FFH was associated with a better CSS; however, the reasons remain unclear. Nevertheless, patients after RP and FFH could be reassured that their own PCa diagnosis is not associated with a worse long-term outcome

Benefit finding in men affected by prostate cancer prior to and following radical prostatectomy – a cross-sectional study with a stratified sample

Abstract Background Benefit finding (BF) - the occurrence of positive life-changes in the aftermath of traumatic live events - has been repeatedly reported in prostate cancer (PCa) survivors, but it remains unclear in which way BF might vary over time. The current study aimed to investigate the extent of BF and associated factors in different phases of the survivorship continuum. Methods In this cross-sectional study, men affected by PCa who were either already treated with radical prostatectomy or going to be treated with radical prostatectomy at a large German PCa center were included. These men were stratified into four groups (prior to surgery, up to 12 months after surgery, 2–5 years and ≥ 6–10 years after surgery). BF was assessed using the German version of the 17-item Benefit Finding Scale (BFS). The items are rated on a five-point Likert scale ranging from 1 to 5. A total mean score ≥ 3 was considered as moderate-to-high BF. Associations with clinical and psychological factors were assessed in men presenting before and in those who participated after surgery. Multiple linear regression was applied to identify intendent determinants of BF. Results 2,298 men affected by PCa (mean age at survey: 69.5,SD = 8.2; median follow-up: 3 years (25th -75th percentile 0.5-7)) were included. 49.6% of men reported moderate-to-high BF. The mean BF score was 2.91 (SD = 0.92). BF reported by men before surgery did not differ significantly from BF reported by men in the years after surgery (p = 0.56). Higher BF prior to and following radical prostatectomy was associated with higher perceived severity of the disease (pre-surgery: ß = 0.188, p = 0.008; post-surgery: ß = 0.161, p = < 0.0001) and higher cancer-related distress (pre-surgery: ß ? 0.155, p = 0.03; post-surgery: ß = 0.089, p < 0.0001). Post radical prostatectomy BF was also associated with biochemical recurrence during follow-up (ß = 0.089, p = 0.001), and higher quality of life (ß = 0.124, p < 0.001). Conclusions Many men affected by PCa perceive BF already soon after diagnosis. The subjective perception of threat or severity associated with the diagnosis of PCa is an essential factor for higher levels of BF, probably more important than objective indicators of the severity of the disease. The early onset of BF and the high degree of similarity of BF reported across the different phases of survivorship suggests that BF is, to a large extent, a dispositional personal characteristic and a cognitive strategy of positively coping with cancer