International Multicenter Validation of an Intermediate Risk Subclassification of Prostate Cancer Managed with Radical Treatment without Hormone Therapy

Berlin, Alejandro; Moraes, F.Y.; Sanmamed, Noelia; Glicksman, Rachel; Koven, Alexander; Espin‐Garcia, Osvaldo; Leite, Elton Trigo Teixeira; Silva, João L F; Gadia, Rafael; Nesbitt, Michael; Catton, Charles; Kaffenberger, Samuel D.; Salami, Simpa S.; Morgan, Todd M.; Hearn, Jason W.D.; Jackson, Will; Mehra, Rohit; Chung, Peter; Fleshner, Neil; Zumsteg, Zachary S.; Dess, Robert T.; Feng, Felix Y.; Finelli, Antonio; Spratt, Daniel E.

doi:10.1016/j.juro.2018.08.044

Cited by 22 publications

(19 citation statements)

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“…Although AS was not explored in that study, it showed a starkly higher risk of metastasis at 10 years in men with CPG3 disease (10-13.5%) than those with CPG2 (0.2-3.5%) depending on the type of radical treatment. That study [30] also, unsurprisingly, showed very different rates of PCM, with results remarkably similar to our own present findings. Based on this, it would seem reasonable that progression to CPG3 is a pragmatic trigger to end AS and switch to treatment.…”

Section: Discussionsupporting

confidence: 92%

“…They are also consistent with results from the randomised Prostate Testing for Cancer and Treatment (ProtecT) trial and other studies whereby the majority of men had low‐ or favourable intermediate‐risk disease without survival differences between treated and untreated men . While the present paper was in preparation, a multicentre study from the USA further showed that the distinction between favourable (CPG2) and unfavourable (CPG3) intermediate‐risk disease also has utility in distinguishing men with different risks of metastasis after radical treatment . Although AS was not explored in that study, it showed a starkly higher risk of metastasis at 10 years in men with CPG3 disease (10–13.5%) than those with CPG2 (0.2–3.5%) depending on the type of radical treatment.…”

Section: Discussionsupporting

confidence: 88%

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Using prognosis to guide inclusion criteria, define standardised endpoints and stratify follow‐up in active surveillance for prostate cancer

et al. 2019

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Objectives To test whether using disease prognosis can inform a rational approach to active surveillance (AS) for early prostate cancer. Patients and methods We previously developed the Cambridge Prognostics Groups (CPG) classification, a five‐tiered model that uses prostate‐specific antigen (PSA), Grade Group and Stage to predict cancer survival outcomes. We applied the CPG model to a UK and a Swedish prostate cancer cohort to test differences in prostate cancer mortality (PCM) in men managed conservatively or by upfront treatment in CPG2 and 3 (which subdivides the intermediate‐risk classification) vs CPG1 (low‐risk). We then applied the CPG model to a contemporary UK AS cohort, which was optimally characterised at baseline for disease burden, to identify predictors of true prognostic progression. Results were re‐tested in an external AS cohort from Spain. Results In a UK cohort (n = 3659) the 10‐year PCM was 2.3% in CPG1, 1.5%/3.5% in treated/untreated CPG2, and 1.9%/8.6% in treated/untreated CPG3. In the Swedish cohort (n = 27 942) the10‐year PCM was 1.0% in CPG1, 2.2%/2.7% in treated/untreated CPG2, and 6.1%/12.5% in treated/untreated CPG3. We then tested using progression to CPG3 as a hard endpoint in a modern AS cohort (n = 133). During follow‐up (median 3.5 years) only 6% (eight of 133) progressed to CPG3. Predictors of progression were a PSA density ≥0.15 ng/mL/mL and CPG2 at diagnosis. Progression occurred in 1%, 8% and 21% of men with neither factor, only one, or both, respectively. In an independent Spanish AS cohort (n = 143) the corresponding rates were 3%, 10% and 14%, respectively. Conclusion Using disease prognosis allows a rational approach to inclusion criteria, discontinuation triggers and risk‐stratified management in AS.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Using prognosis to guide inclusion criteria, define standardised endpoints and stratify follow‐up in active surveillance for prostate cancer

et al. 2019

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“…The study by Berlin et al, which validated Zumsteg et al, included just 258 patients treated with brachytherapy (3). In this group, differences in biochemical recurrence and distant metastasis did not reach statistical significance between the favorable-IR and unfavorable-IR groups, although events rates were low, with only 34 patients having a biochemical recurrence and 18 developing distant metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…These findings were based on 1,024 patients treated with doseescalated external beam radiotherapy (EBRT), and the classification was incorporated into the 2019 NCCN guidelines. Berlin et al validated the sub-classification using an international multi-institutional cohort of 2,550 patients treated with EBRT, radical prostatectomy, and brachytherapy (3). However, there were only 258 (10%) patients in their cohort treated with brachytherapy.…”

Section: Introductionmentioning

confidence: 99%

Validation of the NCCN prostate cancer favorable- and unfavorable-intermediate risk groups among men treated with I-125 low dose rate brachytherapy monotherapy

et al. 2020

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PURPOSE: To validate the 2019 NCCN subgroups of favorable-and unfavorable-intermediate risk (IR) prostate cancer among patients treated with brachytherapy, who are underrepresented in the studies used to develop the 2019 NCCN classification. METHODS: We included all 2,705 men treated with I-125 LDR brachytherapy monotherapy at a single institution, and who could be classified into the 2019 NCCN risk groups. Biochemical failure and distant metastasis rates were calculated using cumulative incidence analysis. RESULTS: Of 1,510 IR patients, 756 (50%) were favorable-IR, and 754 (50%) were unfavorable-IR. Median follow up was 48 months (range, 3e214). As compared to favorable-IR, the unfavorable-IR group was associated with significantly higher rates of biochemical failure (HR, 2.87; 95% CI, 2.00e4.10; p ! 0.001) and distant metastasis (HR, 3.14; 95% CI, 1.78e5.50, p ! 0.001). For favorable-IR vs. unfavorable-IR groups, 5-year estimates of biochemical failure were 4.3% (95% CI, 2.6e6.1%) vs. 17.0% (95% CI, 13.6e20.5%; p ! 0.001), and for distant metastasis were 1.6% (95% CI, 0.5e2.6%) vs. 5.4% (95% CI, 3.3e7.4%; p ! 0.001), respectively. Patients with one unfavorable-intermediate risk factor (unfavorable-IRF; HR, 2.27; 95% CI, 1.54e3.36; p ! 0.001) and 2e3 unfavorable-IRFs (HR, 4.42; 95% CI, 2.89e6.76; p ! 0.001) had higher biochemical failure rates; similar findings were observed for distant metastasis (1 unfavorable-IRF: HR, 2.46; 95% CI, 1.34e4.53, p 5 0.004; 2e3 unfavorable-IRFs: HR, 4.76; 95% CI, 2.49e9.10, p ! 0.001). CONCLUSIONS: These findings validate the prognostic utility of the 2019 NCCN favorable-IR and unfavorable-IR prostate cancer subgroups among men treated with brachytherapy. Androgen deprivation was not beneficial in any subgroup. Alternative treatment intensification strategies for unfavorable-IR patients are warranted.

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“…We emphasize that the creation of risk groups or strata that are relevant to clinical practice is entirely feasible and appropriate once the fundamental components (including TNM categories, biological variables and others) are established. Composite risk or prognostic groups of this type are often helpful, although they also have limitations [35][36][37] . Such risk groups are usually not generalizable across the full spectrum of disease and tend to be specific to anatomy and time-dependent scenarios 21,[38][39][40] .…”

Section: Amalgamation Of Other Prognostic Factorsmentioning

confidence: 99%

Global Consultation on Cancer Staging: promoting consistent understanding and use

et al. 2019

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Disease burden is the most important determinant of survival in patients with cancer. This domain, reflected by the cancer stage and codified using the tumour-node-metastasis (TNM) classification, is a fundamental determinant of prognosis. Accurate and consistent tumour classification is required for the development and use of treatment guidelines and to enable clinical research (including clinical trials), cancer surveillance and control. Furthermore, knowledge of the extent and stage of disease is frequently important in the context of translational studies. Attempts to include additional prognostic factors in staging classifications, in order to facilitate a more accurate determination of prognosis, are often made with a lack of knowledge and understanding and are one of the main causes of the inconsistent use of terms and definitions. This effect has resulted in uncertainty and confusion, thus limiting the utility of the TNM classification. In this Position paper, we provide a consensus on the optimal use and terminology for cancer staging that emerged from a consultation process involving representatives of several major international organizations involved in cancer classification. The consultation involved several steps: a focused literature review; a stakeholder survey ; and a consultation meeting. This aim of this Position paper is to provide a consensus that should guide the use of staging terminology and secure the classification of anatomical disease extent as a distinct aspect of cancer classification.

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International Multicenter Validation of an Intermediate Risk Subclassification of Prostate Cancer Managed with Radical Treatment without Hormone Therapy

Abstract: This multicenter international effort independently validates the prognostic value of the IR-PCa subclassification in ADT-naïve patients across all radical treatment modalities. It is unlikely that treatment intensification will meaningfully improve oncologic outcomes for FIR men.

Cited by 22 publications

References 1 publication

Using prognosis to guide inclusion criteria, define standardised endpoints and stratify follow‐up in active surveillance for prostate cancer

Using prognosis to guide inclusion criteria, define standardised endpoints and stratify follow‐up in active surveillance for prostate cancer

Validation of the NCCN prostate cancer favorable- and unfavorable-intermediate risk groups among men treated with I-125 low dose rate brachytherapy monotherapy

Global Consultation on Cancer Staging: promoting consistent understanding and use

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