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1. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

Author

Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon Y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Offman J., Kote-Jarai Z., Eeles R.A., Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon Y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Offman J., Kote-Jarai Z., and Eeles R.A.

Abstract

BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHOD(S): The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3.0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This

Published
2022

2. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

Author

Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Adams L., Adlard J., Alfonso R., Ali S., Andrew A., Araujo L., Azam N., Ball D., Barker Q., Basevitch A., Benton B., Berlin C., Bermingham N., Biller L., Bloss A., Bradford M., Bradshaw N., Branson A., Brendler C., Brennan M., Bulman B., Burgess L., Cahill D., Callard A., Calvo Verges N., Cardoso M., Carter V., Catanzaro M., Chamberlain A., Chapman C., Chong M., Clark C., Clowes V., Cogley L., Cole T., Compton C., Conner T., Cookson S., Cornford P., Costello P., Coulier L., Davies M., Dechet C., DeSouza B., Devlin G., Douglas F., Douglas E., Dudakia D., Duncan A., Ellery N., Everest S., Freemantle S., Frydenberg M., Fuller D., Gabriel C., Gale M., Garcia L., Gay S., Genova E., George A., Georgiou D., Gisbert A., Gleeson M., Glover W., Gnanapragasam V., Goff S., Goldgar D., Goncalves N., Goodman S., Gorrie J., Gott H., Grant A., Gray C., Griffiths J., Gupwell K., Gurasashvili J., Hanslien E., Haraldsdottir S., Hart R., Hartigan C., Hawkes L., Heaton T., Henderson A., Henrique R., Hilario K., Hill K., Hulick P., Hunt C., Hutchings M., Ibitoye R., Inglehearn T., Ireland J., Islam F., Ismail S., Jacobs C., James D., Jenkins S., Jobson I., Johnstone A., Jones O., Josefsberg Ben-Yehoshua S., Kaemba B., Kaul K., Kemp Z., Kinsella N., Klehm M., Kockelbergh R., Kohut K., Kosicka-Slawinska M., Kulkarni A., Kumar P., Lam J., LeButt M., Leibovici D., Lim R., Limb L., Lomas C., Longmuir M., Lopez C., Magnani T., Maia S., Maiden J., Male A., Manalo M., Martin P., McBride D., McGuire M., McMahon R., McNally C., McVeigh T., Melzer E., Mencias M., Mercer C., Mitchell G., Mora J., Morton C., Moss C., Murphy M., Murphy D., Mzazi S., Nadolski M., Newlin A., Nogueira P., O'Keefe R., O'Toole K., O'Connell S., Ogden C., Okoth L., Oliveira J., Paez E., Palou J., Park L., Patel N., Paulo Souto J., Pearce A., Peixoto A., Perez K., Petelin L., Pichert G., Poile C., Potter A., Preitner N., Purnell H., Quinn E., Radice P., Rankin B., Rees K., Renton C., Richardson K., Risby P., Rogers J., Ruderman M., Ruiz A., Sajoo A., Salvatore N., Sands V., Sanguedolce F., Sattar A., Saunders K., Schofield L., Scott R., Searle A., Sehra R., Selkirk C., Shackleton K., Shanley S., Shaw A., Shevrin D., Shipman H., Sidat Z., Siguake K., Simon K., Smyth C., Snadden L., Solanky N., Solomons J., Sorrentino M., Stayner B., Stephenson R., Stoffel E., Thomas M., Thompson A., Tidey L., Tischkowitz M., Torokwa A., Townshend S., Treherne K., Tricker K., Trinh Q.-D., Tripathi V., Turnbull C., Valdagni R., Van As N., Venne V., Verdon L., Vitellaro M., Vogel K., Walker L., Watford A., Watt C., Weintroub I., Weiss S., Weissman S., Weston M., Wiggins J., Wise G., Woodhouse C., Yesildag P., Youngs A., Yurgelun M., Zollo F., Offman J., Kote-Jarai Z., Eeles R.A., Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Adams L., Adlard J., Alfonso R., Ali S., Andrew A., Araujo L., Azam N., Ball D., Barker Q., Basevitch A., Benton B., Berlin C., Bermingham N., Biller L., Bloss A., Bradford M., Bradshaw N., Branson A., Brendler C., Brennan M., Bulman B., Burgess L., Cahill D., Callard A., Calvo Verges N., Cardoso M., Carter V., Catanzaro M., Chamberlain A., Chapman C., Chong M., Clark C., Clowes V., Cogley L., Cole T., Compton C., Conner T., Cookson S., Cornford P., Costello P., Coulier L., Davies M., Dechet C., DeSouza B., Devlin G., Douglas F., Douglas E., Dudakia D., Duncan A., Ellery N., Everest S., Freemantle S., Frydenberg M., Fuller D., Gabriel C., Gale M., Garcia L., Gay S., Genova E., George A., Georgiou D., Gisbert A., Gleeson M., Glover W., Gnanapragasam V., Goff S., Goldgar D., Goncalves N., Goodman S., Gorrie J., Gott H., Grant A., Gray C., Griffiths J., Gupwell K., Gurasashvili J., Hanslien E., Haraldsdottir S., Hart R., Hartigan C., Hawkes L., Heaton T., Henderson A., Henrique R., Hilario K., Hill K., Hulick P., Hunt C., Hutchings M., Ibitoye R., Inglehearn T., Ireland J., Islam F., Ismail S., Jacobs C., James D., Jenkins S., Jobson I., Johnstone A., Jones O., Josefsberg Ben-Yehoshua S., Kaemba B., Kaul K., Kemp Z., Kinsella N., Klehm M., Kockelbergh R., Kohut K., Kosicka-Slawinska M., Kulkarni A., Kumar P., Lam J., LeButt M., Leibovici D., Lim R., Limb L., Lomas C., Longmuir M., Lopez C., Magnani T., Maia S., Maiden J., Male A., Manalo M., Martin P., McBride D., McGuire M., McMahon R., McNally C., McVeigh T., Melzer E., Mencias M., Mercer C., Mitchell G., Mora J., Morton C., Moss C., Murphy M., Murphy D., Mzazi S., Nadolski M., Newlin A., Nogueira P., O'Keefe R., O'Toole K., O'Connell S., Ogden C., Okoth L., Oliveira J., Paez E., Palou J., Park L., Patel N., Paulo Souto J., Pearce A., Peixoto A., Perez K., Petelin L., Pichert G., Poile C., Potter A., Preitner N., Purnell H., Quinn E., Radice P., Rankin B., Rees K., Renton C., Richardson K., Risby P., Rogers J., Ruderman M., Ruiz A., Sajoo A., Salvatore N., Sands V., Sanguedolce F., Sattar A., Saunders K., Schofield L., Scott R., Searle A., Sehra R., Selkirk C., Shackleton K., Shanley S., Shaw A., Shevrin D., Shipman H., Sidat Z., Siguake K., Simon K., Smyth C., Snadden L., Solanky N., Solomons J., Sorrentino M., Stayner B., Stephenson R., Stoffel E., Thomas M., Thompson A., Tidey L., Tischkowitz M., Torokwa A., Townshend S., Treherne K., Tricker K., Trinh Q.-D., Tripathi V., Turnbull C., Valdagni R., Van As N., Venne V., Verdon L., Vitellaro M., Vogel K., Walker L., Watford A., Watt C., Weintroub I., Weiss S., Weissman S., Weston M., Wiggins J., Wise G., Woodhouse C., Yesildag P., Youngs A., Yurgelun M., Zollo F., Offman J., Kote-Jarai Z., and Eeles R.A.

Abstract

Background: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. Method(s): The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3.0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This

Published
2022

3. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

Author

Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon Y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Offman J., Kote-Jarai Z., Eeles R.A., Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon Y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Offman J., Kote-Jarai Z., and Eeles R.A.

Abstract

BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHOD(S): The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3.0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This

Published
2022

4. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

Author

Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Adams L., Adlard J., Alfonso R., Ali S., Andrew A., Araujo L., Azam N., Ball D., Barker Q., Basevitch A., Benton B., Berlin C., Bermingham N., Biller L., Bloss A., Bradford M., Bradshaw N., Branson A., Brendler C., Brennan M., Bulman B., Burgess L., Cahill D., Callard A., Calvo Verges N., Cardoso M., Carter V., Catanzaro M., Chamberlain A., Chapman C., Chong M., Clark C., Clowes V., Cogley L., Cole T., Compton C., Conner T., Cookson S., Cornford P., Costello P., Coulier L., Davies M., Dechet C., DeSouza B., Devlin G., Douglas F., Douglas E., Dudakia D., Duncan A., Ellery N., Everest S., Freemantle S., Frydenberg M., Fuller D., Gabriel C., Gale M., Garcia L., Gay S., Genova E., George A., Georgiou D., Gisbert A., Gleeson M., Glover W., Gnanapragasam V., Goff S., Goldgar D., Goncalves N., Goodman S., Gorrie J., Gott H., Grant A., Gray C., Griffiths J., Gupwell K., Gurasashvili J., Hanslien E., Haraldsdottir S., Hart R., Hartigan C., Hawkes L., Heaton T., Henderson A., Henrique R., Hilario K., Hill K., Hulick P., Hunt C., Hutchings M., Ibitoye R., Inglehearn T., Ireland J., Islam F., Ismail S., Jacobs C., James D., Jenkins S., Jobson I., Johnstone A., Jones O., Josefsberg Ben-Yehoshua S., Kaemba B., Kaul K., Kemp Z., Kinsella N., Klehm M., Kockelbergh R., Kohut K., Kosicka-Slawinska M., Kulkarni A., Kumar P., Lam J., LeButt M., Leibovici D., Lim R., Limb L., Lomas C., Longmuir M., Lopez C., Magnani T., Maia S., Maiden J., Male A., Manalo M., Martin P., McBride D., McGuire M., McMahon R., McNally C., McVeigh T., Melzer E., Mencias M., Mercer C., Mitchell G., Mora J., Morton C., Moss C., Murphy M., Murphy D., Mzazi S., Nadolski M., Newlin A., Nogueira P., O'Keefe R., O'Toole K., O'Connell S., Ogden C., Okoth L., Oliveira J., Paez E., Palou J., Park L., Patel N., Paulo Souto J., Pearce A., Peixoto A., Perez K., Petelin L., Pichert G., Poile C., Potter A., Preitner N., Purnell H., Quinn E., Radice P., Rankin B., Rees K., Renton C., Richardson K., Risby P., Rogers J., Ruderman M., Ruiz A., Sajoo A., Salvatore N., Sands V., Sanguedolce F., Sattar A., Saunders K., Schofield L., Scott R., Searle A., Sehra R., Selkirk C., Shackleton K., Shanley S., Shaw A., Shevrin D., Shipman H., Sidat Z., Siguake K., Simon K., Smyth C., Snadden L., Solanky N., Solomons J., Sorrentino M., Stayner B., Stephenson R., Stoffel E., Thomas M., Thompson A., Tidey L., Tischkowitz M., Torokwa A., Townshend S., Treherne K., Tricker K., Trinh Q.-D., Tripathi V., Turnbull C., Valdagni R., Van As N., Venne V., Verdon L., Vitellaro M., Vogel K., Walker L., Watford A., Watt C., Weintroub I., Weiss S., Weissman S., Weston M., Wiggins J., Wise G., Woodhouse C., Yesildag P., Youngs A., Yurgelun M., Zollo F., Offman J., Kote-Jarai Z., Eeles R.A., Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Adams L., Adlard J., Alfonso R., Ali S., Andrew A., Araujo L., Azam N., Ball D., Barker Q., Basevitch A., Benton B., Berlin C., Bermingham N., Biller L., Bloss A., Bradford M., Bradshaw N., Branson A., Brendler C., Brennan M., Bulman B., Burgess L., Cahill D., Callard A., Calvo Verges N., Cardoso M., Carter V., Catanzaro M., Chamberlain A., Chapman C., Chong M., Clark C., Clowes V., Cogley L., Cole T., Compton C., Conner T., Cookson S., Cornford P., Costello P., Coulier L., Davies M., Dechet C., DeSouza B., Devlin G., Douglas F., Douglas E., Dudakia D., Duncan A., Ellery N., Everest S., Freemantle S., Frydenberg M., Fuller D., Gabriel C., Gale M., Garcia L., Gay S., Genova E., George A., Georgiou D., Gisbert A., Gleeson M., Glover W., Gnanapragasam V., Goff S., Goldgar D., Goncalves N., Goodman S., Gorrie J., Gott H., Grant A., Gray C., Griffiths J., Gupwell K., Gurasashvili J., Hanslien E., Haraldsdottir S., Hart R., Hartigan C., Hawkes L., Heaton T., Henderson A., Henrique R., Hilario K., Hill K., Hulick P., Hunt C., Hutchings M., Ibitoye R., Inglehearn T., Ireland J., Islam F., Ismail S., Jacobs C., James D., Jenkins S., Jobson I., Johnstone A., Jones O., Josefsberg Ben-Yehoshua S., Kaemba B., Kaul K., Kemp Z., Kinsella N., Klehm M., Kockelbergh R., Kohut K., Kosicka-Slawinska M., Kulkarni A., Kumar P., Lam J., LeButt M., Leibovici D., Lim R., Limb L., Lomas C., Longmuir M., Lopez C., Magnani T., Maia S., Maiden J., Male A., Manalo M., Martin P., McBride D., McGuire M., McMahon R., McNally C., McVeigh T., Melzer E., Mencias M., Mercer C., Mitchell G., Mora J., Morton C., Moss C., Murphy M., Murphy D., Mzazi S., Nadolski M., Newlin A., Nogueira P., O'Keefe R., O'Toole K., O'Connell S., Ogden C., Okoth L., Oliveira J., Paez E., Palou J., Park L., Patel N., Paulo Souto J., Pearce A., Peixoto A., Perez K., Petelin L., Pichert G., Poile C., Potter A., Preitner N., Purnell H., Quinn E., Radice P., Rankin B., Rees K., Renton C., Richardson K., Risby P., Rogers J., Ruderman M., Ruiz A., Sajoo A., Salvatore N., Sands V., Sanguedolce F., Sattar A., Saunders K., Schofield L., Scott R., Searle A., Sehra R., Selkirk C., Shackleton K., Shanley S., Shaw A., Shevrin D., Shipman H., Sidat Z., Siguake K., Simon K., Smyth C., Snadden L., Solanky N., Solomons J., Sorrentino M., Stayner B., Stephenson R., Stoffel E., Thomas M., Thompson A., Tidey L., Tischkowitz M., Torokwa A., Townshend S., Treherne K., Tricker K., Trinh Q.-D., Tripathi V., Turnbull C., Valdagni R., Van As N., Venne V., Verdon L., Vitellaro M., Vogel K., Walker L., Watford A., Watt C., Weintroub I., Weiss S., Weissman S., Weston M., Wiggins J., Wise G., Woodhouse C., Yesildag P., Youngs A., Yurgelun M., Zollo F., Offman J., Kote-Jarai Z., and Eeles R.A.

Abstract

Background: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. Method(s): The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3.0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This

Published
2022

5. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

Author

Izatt L., Davidson R., Ruijs M., Helderman-Van Den Enden A.T., Andrews L., Walker L., Snape K., Henderson A., Jobson I., Lindeman G.J., Liljegren A., Harris M., Adank M.A., Kirk J., Taylor A., Susman R., Chen-Shtoyerman R., Pachter N., Spigelman A., Side L., Zgajnar J., Mora J., Brewer C., Gadea N., Brady A.F., Gallagher D., Van Os T., Donaldson A., Stefansdottir V., Barwell J., James P.A., Murphy D., Friedman E., Nicolai N., Greenhalgh L., Obeid E., Murthy V., Copakova L., McGrath J., Teo S.-H., Strom S., Kast K., Leongamornlert D.A., Chamberlain A., Pope J., Newlin A.C., Aaronson N., Ardern-Jones A., Bangma C., Castro E., Dearnaley D., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lubinski J., Grindedal E.M., McKinley J., Shackleton K., Mitra A.V., Moynihan C., Rennert G., Suri M., Tricker K., Moss S., Kote-Jarai Z., Vickers A., Lilja H., Helfand B.T., Eeles R.A., Mikropoulos C., Selkirk C.G.H., Saya S., Bancroft E., Vertosick E., Dadaev T., Brendler C., Page E., Dias A., Evans D.G., Rothwell J., Maehle L., Axcrona K., Richardson K., Eccles D., Jensen T., Osther P.J., Van Asperen C.J., Vasen H., Kiemeney L.A., Ringelberg J., Cybulski C., Wokolorczyk D., Hart R., Glover W., Lam J., Taylor L., Salinas M., Feliubadalo L., Oldenburg R., Cremers R., Verhaegh G., Van Zelst-Stams W.A., Oosterwijk J.C., Cook J., Rosario D.J., Buys S.S., Conner T., Domchek S., Powers J., Ausems M.G., Teixeira M.R., Maia S., Schmutzler R., Rhiem K., Foulkes W.D., Boshari T., Izatt L., Davidson R., Ruijs M., Helderman-Van Den Enden A.T., Andrews L., Walker L., Snape K., Henderson A., Jobson I., Lindeman G.J., Liljegren A., Harris M., Adank M.A., Kirk J., Taylor A., Susman R., Chen-Shtoyerman R., Pachter N., Spigelman A., Side L., Zgajnar J., Mora J., Brewer C., Gadea N., Brady A.F., Gallagher D., Van Os T., Donaldson A., Stefansdottir V., Barwell J., James P.A., Murphy D., Friedman E., Nicolai N., Greenhalgh L., Obeid E., Murthy V., Copakova L., McGrath J., Teo S.-H., Strom S., Kast K., Leongamornlert D.A., Chamberlain A., Pope J., Newlin A.C., Aaronson N., Ardern-Jones A., Bangma C., Castro E., Dearnaley D., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lubinski J., Grindedal E.M., McKinley J., Shackleton K., Mitra A.V., Moynihan C., Rennert G., Suri M., Tricker K., Moss S., Kote-Jarai Z., Vickers A., Lilja H., Helfand B.T., Eeles R.A., Mikropoulos C., Selkirk C.G.H., Saya S., Bancroft E., Vertosick E., Dadaev T., Brendler C., Page E., Dias A., Evans D.G., Rothwell J., Maehle L., Axcrona K., Richardson K., Eccles D., Jensen T., Osther P.J., Van Asperen C.J., Vasen H., Kiemeney L.A., Ringelberg J., Cybulski C., Wokolorczyk D., Hart R., Glover W., Lam J., Taylor L., Salinas M., Feliubadalo L., Oldenburg R., Cremers R., Verhaegh G., Van Zelst-Stams W.A., Oosterwijk J.C., Cook J., Rosario D.J., Buys S.S., Conner T., Domchek S., Powers J., Ausems M.G., Teixeira M.R., Maia S., Schmutzler R., Rhiem K., Foulkes W.D., and Boshari T.

Abstract

Background:Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. Method(s):PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. Result(s):1634 participants had 3/43 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml -l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. Conclusion(s):PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

Published
2018

6. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

Author

Izatt L., Davidson R., Ruijs M., Helderman-Van Den Enden A.T., Andrews L., Walker L., Snape K., Henderson A., Jobson I., Lindeman G.J., Liljegren A., Harris M., Adank M.A., Kirk J., Taylor A., Susman R., Chen-Shtoyerman R., Pachter N., Spigelman A., Side L., Zgajnar J., Mora J., Brewer C., Gadea N., Brady A.F., Gallagher D., Van Os T., Donaldson A., Stefansdottir V., Barwell J., James P.A., Murphy D., Friedman E., Nicolai N., Greenhalgh L., Obeid E., Murthy V., Copakova L., McGrath J., Teo S.-H., Strom S., Kast K., Leongamornlert D.A., Chamberlain A., Pope J., Newlin A.C., Aaronson N., Ardern-Jones A., Bangma C., Castro E., Dearnaley D., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lubinski J., Grindedal E.M., McKinley J., Shackleton K., Mitra A.V., Moynihan C., Rennert G., Suri M., Tricker K., Moss S., Kote-Jarai Z., Vickers A., Lilja H., Helfand B.T., Eeles R.A., Mikropoulos C., Selkirk C.G.H., Saya S., Bancroft E., Vertosick E., Dadaev T., Brendler C., Page E., Dias A., Evans D.G., Rothwell J., Maehle L., Axcrona K., Richardson K., Eccles D., Jensen T., Osther P.J., Van Asperen C.J., Vasen H., Kiemeney L.A., Ringelberg J., Cybulski C., Wokolorczyk D., Hart R., Glover W., Lam J., Taylor L., Salinas M., Feliubadalo L., Oldenburg R., Cremers R., Verhaegh G., Van Zelst-Stams W.A., Oosterwijk J.C., Cook J., Rosario D.J., Buys S.S., Conner T., Domchek S., Powers J., Ausems M.G., Teixeira M.R., Maia S., Schmutzler R., Rhiem K., Foulkes W.D., Boshari T., Izatt L., Davidson R., Ruijs M., Helderman-Van Den Enden A.T., Andrews L., Walker L., Snape K., Henderson A., Jobson I., Lindeman G.J., Liljegren A., Harris M., Adank M.A., Kirk J., Taylor A., Susman R., Chen-Shtoyerman R., Pachter N., Spigelman A., Side L., Zgajnar J., Mora J., Brewer C., Gadea N., Brady A.F., Gallagher D., Van Os T., Donaldson A., Stefansdottir V., Barwell J., James P.A., Murphy D., Friedman E., Nicolai N., Greenhalgh L., Obeid E., Murthy V., Copakova L., McGrath J., Teo S.-H., Strom S., Kast K., Leongamornlert D.A., Chamberlain A., Pope J., Newlin A.C., Aaronson N., Ardern-Jones A., Bangma C., Castro E., Dearnaley D., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lubinski J., Grindedal E.M., McKinley J., Shackleton K., Mitra A.V., Moynihan C., Rennert G., Suri M., Tricker K., Moss S., Kote-Jarai Z., Vickers A., Lilja H., Helfand B.T., Eeles R.A., Mikropoulos C., Selkirk C.G.H., Saya S., Bancroft E., Vertosick E., Dadaev T., Brendler C., Page E., Dias A., Evans D.G., Rothwell J., Maehle L., Axcrona K., Richardson K., Eccles D., Jensen T., Osther P.J., Van Asperen C.J., Vasen H., Kiemeney L.A., Ringelberg J., Cybulski C., Wokolorczyk D., Hart R., Glover W., Lam J., Taylor L., Salinas M., Feliubadalo L., Oldenburg R., Cremers R., Verhaegh G., Van Zelst-Stams W.A., Oosterwijk J.C., Cook J., Rosario D.J., Buys S.S., Conner T., Domchek S., Powers J., Ausems M.G., Teixeira M.R., Maia S., Schmutzler R., Rhiem K., Foulkes W.D., and Boshari T.

Abstract

Background:Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. Method(s):PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. Result(s):1634 participants had 3/43 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml -l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. Conclusion(s):PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

Published
2018

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