. 2022 Jul 22;14(15):3558.

doi: 10.3390/cancers14153558.

Adverse Pathological Findings at Radical Prostatectomy following Active Surveillance: Results from the Movember GAP3 Cohort

Cristina Marenghi¹, Zhuyu Qiu^{2

3

4

5}, Jozien Helleman⁶, Daan Nieboer^{6

7}, Josè Rubio-Briones⁸, Peter R Carroll⁹, Lui Shiong Lee¹⁰, Riccardo Valdagni^{1

11

12}, Paul C Boutros^{2

3

4

5}, Nicola Nicolai¹³; Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance (GAP3) Consortium

Collaborators, Affiliations

Collaborators

Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance (GAP3) Consortium:
Bruce Trock, Steyerberg Ewout, Jenster Guido, Kouspou Michelle, Tom Pickles, Wei Guo, Aida Santaolalla, Alexandre Mamedov, Anders Bjartell, Andrew Hayen, Ann Arbor, Annica Löfgren, Anssi Auvinen, Antoinette Perry, Antti Rannikko, Arnauld Villers, Axel Semjonow, Behfar Ehdaie, Boris Ruwe, Brian Denton, Caroline Moore, Chris Bangma, Christopher Filson, Christopher Logothetis, Daan Nieboer, Dattatraya Patil, Eric Hyndman, Grégoire Robert, Helén Ahlgren, Hiromi Hirama, Janet Cowan, Jenna Kimberly-Duffell, Jonas Hugosson, Jonathan Olivier, Jose Rubio-Briones, Jozien Helleman, Juanma Mascarós, Kellie Paich, Kerri Beckmann, Kurt Lehmann, Lauren Park, Laurence Klotz, Lukas Hefermehl, Mark Frydenberg, Masoom Haider, Mikio Sugimoto, Monique Roobol, Nicole Benfante, Paul Boutros, Peter Carroll, Phillip Stricker, Prokar Dasgupta, Riccardo Valdagni, Stephanie Ferrante, Thomas Cusick, Tim Hulsen, Tiziana Rancati, Todd Morgan, Trafford Crump, Vasilis Stavrinides, Vincent Gnanapragasam, Vincent LaPointe, Wim Van der Linden, Byung Ha Chung, Catherine Han Lin, Lee Lui Shiong, Mieke Van Hemelrijck, Peter Van Hooft, Theo Van der Kwast, Kees Van Bochove, Lee Kwang Suk

Affiliations

¹ Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
² Department of Human Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Urology, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁴ Jonsson Comprehensive Cancer Centre, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁵ Institute for Precision Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁶ Department of Urology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands.
⁷ Department of Public Health, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands.
⁸ Department of Urology, Hospital VITHAS 9 de Octubre, 46025 Valencia, Spain.
⁹ Department of Urology, University of California, San Francisco, CA 94158, USA.
¹⁰ Department of Urology, Sengkang General Hospital and Singapore General Hospital, Singapore 544886, Singapore.
¹¹ Department of Oncology and Hemato-Oncology, Università Degli Studi di Milano, 20132 Milan, Italy.
¹² Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
¹³ Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.

PMID: 35892817
PMCID: PMC9332009
DOI: 10.3390/cancers14153558

Adverse Pathological Findings at Radical Prostatectomy following Active Surveillance: Results from the Movember GAP3 Cohort

Cristina Marenghi et al. Cancers (Basel). 2022.

. 2022 Jul 22;14(15):3558.

doi: 10.3390/cancers14153558.

Authors

Collaborators

Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance (GAP3) Consortium:
Bruce Trock, Steyerberg Ewout, Jenster Guido, Kouspou Michelle, Tom Pickles, Wei Guo, Aida Santaolalla, Alexandre Mamedov, Anders Bjartell, Andrew Hayen, Ann Arbor, Annica Löfgren, Anssi Auvinen, Antoinette Perry, Antti Rannikko, Arnauld Villers, Axel Semjonow, Behfar Ehdaie, Boris Ruwe, Brian Denton, Caroline Moore, Chris Bangma, Christopher Filson, Christopher Logothetis, Daan Nieboer, Dattatraya Patil, Eric Hyndman, Grégoire Robert, Helén Ahlgren, Hiromi Hirama, Janet Cowan, Jenna Kimberly-Duffell, Jonas Hugosson, Jonathan Olivier, Jose Rubio-Briones, Jozien Helleman, Juanma Mascarós, Kellie Paich, Kerri Beckmann, Kurt Lehmann, Lauren Park, Laurence Klotz, Lukas Hefermehl, Mark Frydenberg, Masoom Haider, Mikio Sugimoto, Monique Roobol, Nicole Benfante, Paul Boutros, Peter Carroll, Phillip Stricker, Prokar Dasgupta, Riccardo Valdagni, Stephanie Ferrante, Thomas Cusick, Tim Hulsen, Tiziana Rancati, Todd Morgan, Trafford Crump, Vasilis Stavrinides, Vincent Gnanapragasam, Vincent LaPointe, Wim Van der Linden, Byung Ha Chung, Catherine Han Lin, Lee Lui Shiong, Mieke Van Hemelrijck, Peter Van Hooft, Theo Van der Kwast, Kees Van Bochove, Lee Kwang Suk

Affiliations

¹ Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
² Department of Human Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Urology, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁴ Jonsson Comprehensive Cancer Centre, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁵ Institute for Precision Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁶ Department of Urology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands.
⁷ Department of Public Health, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands.
⁸ Department of Urology, Hospital VITHAS 9 de Octubre, 46025 Valencia, Spain.
⁹ Department of Urology, University of California, San Francisco, CA 94158, USA.
¹⁰ Department of Urology, Sengkang General Hospital and Singapore General Hospital, Singapore 544886, Singapore.
¹¹ Department of Oncology and Hemato-Oncology, Università Degli Studi di Milano, 20132 Milan, Italy.
¹² Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
¹³ Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.

PMID: 35892817
PMCID: PMC9332009
DOI: 10.3390/cancers14153558

Abstract

Background: Little is known about the consequences of delaying radical prostatectomy (RP) after Active Surveillance (AS) according to stringent or wider entry criteria. We investigated the association between inclusion criteria and rates, and timing of adverse pathological findings (APFs) among patients in GAP3 cohorts. Methods: APFs (GG ≥ 3, pT ≥ 3, pN > 0 and positive surgical margins [R1]) were accounted for in very low-risk (VLR: grade group [GG] 1, cT1, positive cores < 3, PSA < 10 ng/mL, PSA density [PSAD] < 0.15 ng/mL/cm3) and low-risk (LR: GG1, cT1-2, PSA ≤ 10 ng/mL) patients undergoing subsequent RP. The Kaplan−Meier method and log−rank test analyzed APF-free survival. Stratified mixed effects models analyzed association. Results: Out of 21,169 patients on AS, 1742 (VLR: 721; LR: 1021) underwent delayed RP. Most (60.8%) did not have APFs. APFs occurred more frequently (44.6% vs. 31.7%; OR 1.54, p < 0.001) and earlier (median time: 40.3 vs. 62.6 months; p < 0.001) in LR patients, and consisted of pT ≥ 3 (OR 1.47, p = 0.013) or R1 (OR 1.80, p < 0.001), but not of GG ≥ 3 or node involvement. Age (OR 1.05, p < 0.001), PSAD (OR 23.21, p = 0.003), and number of positive cores (OR 1.16, p = 0.004) were independently associated with APFs. Conclusions: AS stands as a safe option for low-risk patients, and most do not have APFs at surgery. Wider entry criteria are associated with pT3 and R1. The prognostic implications remain uncertain.

Keywords: active surveillance; classification; outcome; pathology; prognosis; prostatectomy; prostatic neoplasms; risk assessment; watchful waiting.

PubMed Disclaimer

Conflict of interest statement

Paul C. Boutros sits on the scientific advisory boards of Sage Bionetworks, Intersect Diagnostics Inc., and BioSymetrics Inc. The other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

**Figure 1**
CONSORT flow diagram showing the selection process of the study population from the whole GAP3 AS cohort.

See this image and copyright information in PMC

References

1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
1. Albertsen P.C., Hanley J.A., Fine J. 20-Year Outcomes Following Conservative Management of Clinically Localized Prostate Cancer. JAMA. 2005;293:2095–2101. doi: 10.1001/jama.293.17.2095. - DOI - PubMed
1. Lardas M., Liew M., Van den Bergh R.C., De Santis M., Bellmunt J., Van den Broeck T., Cornford P., Cumberbatch M.G., Fossati N., Gross T., et al. Quality of Life Outcomes after Primary Treatment for Clinically Localised Prostate Cancer: A Systematic Review. Eur. Urol. 2017;72:869–885. doi: 10.1016/j.eururo.2017.06.035. - DOI - PubMed
1. Vernooij R.W., Lancee M., Cleves A., Dahm P., Bangma C.H., Aben K.K. Radical prostatectomy versus deferred treatment for localised prostate cancer. Cochrane Database Syst. Rev. 2020;6:CD006590. doi: 10.1002/14651858.CD006590. - DOI - PMC - PubMed
1. Bill-Axelson A., Holmberg L., Garmo H., Taari K., Busch C., Nordling S., Häggman M., Andersson S.-O., Andrén O., Steineck G., et al. Radical Prostatectomy or Watchful Waiting in Prostate Cancer—29-Year Follow-up. N. Engl. J. Med. 2018;379:2319–2329. doi: 10.1056/NEJMoa1807801. - DOI - PubMed

Grants and funding

GAP3/Movember Foundation

LinkOut - more resources

Full Text Sources
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Adverse Pathological Findings at Radical Prostatectomy following Active Surveillance: Results from the Movember GAP3 Cohort

Collaborators

Affiliations

Adverse Pathological Findings at Radical Prostatectomy following Active Surveillance: Results from the Movember GAP3 Cohort

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous