Clinical trial NCT06798558: Neoadjuvant Lu-177-PSMA-617 in Patients With High Risk Localized Prostate Cancer Undergoing Radical Prostatectomy
Official title: Phase II Study of Neoadjuvant Lu-177-PSMA-617 in Patients With High Risk Localized Prostate Cancer Undergoing Radical Prostatectomy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostate Adenocarcinoma
Lead sponsor: Hackensack Meridian Health
Sponsor class: OTHER
Collaborators: name: Lombardi Comprehensive Cancer Center
name: Novartis
First posted: 2025-01-29
Enrollment: 54
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Male adults with a confirmed diagnosis of prostate adenocarcinoma who meet criteria for localized high risk prostate cancer according to the NCCN guidelines and who are eligible for prostatectomy will be invited to participate. Criteria for high-risk prostate cancer include patients with preoperative prostate biopsy score of Gleason 8 (GS8) (Grade group 4 \[GG4\]) or higher. Patients also need to have a positive PSMA scan on 68-Ga-PSMA-11 PET/CT scan.

Detailed description: The PRELUDE trial is a prospective, non-randomized, single-arm, phase 2 interventional study to assess the oncological outcomes after 2 cycles of Lu-177-PSMA-617 (PluvictoⓇ) administered at 6-week intervals before prostatectomy in patients with high risk localized prostate cancer.

Patients who meet all the inclusion criteria for the study will be enrolled to receive 2 cycles of Lu-177-PSMA-617 (PluvictoⓇ) administered at the dose of 7.4 GBq (±10%), once every 6 weeks (±1 week). Six weeks after the second cycle of Lu-177-PSMA-617 (PluvictoⓇ), patients will be eligible for radical prostatectomy with pelvic lymph node dissection and remain eligible for surgery up until 30 days from this timepoint.

Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety at week 3, 6, 9, 11, and 12 as well as a 30-day safety follow-up visit (FUP) and longer term safety follow-up assessments every 3 months for a period of approximately 2 years. Patients who experience disease progression will be managed according to standard treatment guidelines recommendations.

Eligibility criteria: Inclusion Criteria:

* Patients age 18 or older.
* Patients with histologically confirmed adenocarcinoma of the prostate.
* Patients with high-risk disease defined as a preoperative prostate biopsy of Gleason Score 8 (GS8) (Grade group 4 \[GG4\]) or higher. Men with evidence of lymph node involvement at or below the bifurcation of the common iliac arteries (cN1) on PET-CT 68Ga-PSMA-11 are eligible.
* Pre-operative, pre-treatment PSMA scan with high expression in prostate confirmed by PET/CT 68Ga-PSMA-11 (greater than liver). Patients must not have any other PET FDG-positive sites outside the prostate.
* Patients who are able and willing to undergo surgery.
* Patients with a life expectancy of greater than 10 years. Life expectancy can be estimated using any 1 of the following tools:

  * The Social Security Administration tables:

https://www.ssa.gov/OACT/STATS/table4c6.html

* The WHO's Life Tables by country:

https://apps.who.int/gho/data/view.main.60000?lang=en

* The Memorial Sloan Kettering Male Life Expectancy tool:

https://www.mskcc.org/nomograms/prostate

* If using a life expectancy table, life expectancy should be adjusted using the clinician's assessment of overall health as follows: best quartile of health - add 50%; worst quartile of health - subtract 50%; and middle two quartiles of health - no adjustment. See the NCCN Prostate Cancer Guidelines for more information.

  * Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  * Patients who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm, as defined below:
* With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \&amp;amp;lt; 1% per year during the treatment period and for 14 weeks after the final dose of study treatment. Men must refrain from donating sperm during this same period.
* With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 14 weeks after the final dose of study treatment to avoid potential exposure to the embryo.
* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of contraception.

  * Patients who are able to comply with follow-up visits and treatment plans.
  * Patients who are able to give informed consent.

Exclusion Criteria:

* Patients with a prior history of prostate cancer treatment.
* Patients with previous treatment with PSMA-targeted radioligand therapy or any of the following within 6 months of enrollment confirmation: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation.
* Patients with distant disease (outside of local lymph nodes).
* Significant bone marrow impairment defined by leukocytes \&amp;amp;lt;3,000/mcL, absolute neutrophil count (ANC) \&amp;amp;lt;1,500/mcL, and platelet count lower than 70,000/mcL.
* Significant liver function impairment defined by total bilirubin higher than 1.5 times the upper limit of normal (ULN), andASL/ALT higher than 3 times the ULN.
* Impaired kidney function defined by glomerular filtration rate (GFR) lower than 40 mL/min, or concomitant use of nephrotoxic drugs. Kidney function based on eGFR by Modification of Diet in Renal Disease (MDRD) equation:

  * Normal renal function: participants with eGFR 90 mL/min
  * Moderate renal impairment: participants with eGFR 30 to 59 mL/min
  * Severe renal impairment: participants with eGFR 15 to 29 mL/min
* Patients with significant comorbidities that would make them poor candidates for surgery.
* Patients with evidence of metastatic disease (enlarged lymph nodes, distant metastatic sites, visceral or bone metastases, etc.).
* Patients with a history of radiation or hormone therapy to the prostate.
* Patients with a history of bleeding disorders or who are taking anticoagulant therapy.
* Patients with active infections or other contraindications for surgery.
* Patients who are unable or unwilling to give informed consent.
* Patients who are unable to comply with follow-up visits and treatment plans

Primary outcomes:
measure: Prostate cancer down-staging following treatment with Lu-177-PSMA-617 (PluvictoⓇ) defined by Gleason Grade Group
timeFrame: Patients will undergo a PSMA PET/CT scans up to week 11 +/- 30 days prior to radical prostatectomy with pelvic lymph node dissection.
Secondary outcomes:
measure: Prostate cancer down-staging following treatment with Lu-177-PSMA-617 (PluvictoⓇ) as defined by margin status, T staging, and seminal vesicle involvement
timeFrame: Patients will undergo a PSMA PET/CT scans up to week 11 +/- 30 days prior to radical prostatectomy with pelvic lymph node dissection.
measure: Decrease in PSMA-avid tumor load
timeFrame: Patients will undergo a SOC PSMA PET/CT scans up to week 11 +/- 30 days prior to radical prostatectomy with pelvic lymph node dissection.
measure: Safety of radical prostatectomy assessed by surgical delay time
timeFrame: Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
measure: Safety of radical prostatectomy assessed by rate of intraoperative and postoperative complications
timeFrame: Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
measure: Safety of radical prostatectomy assessed by the amount of blood loss
timeFrame: Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
measure: Safety of radical prostatectomy assessed by percentage of periprostatic adhesion
timeFrame: Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
measure: Safety of radical prostatectomy assessed by the surgical length of time
timeFrame: Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
measure: Quality-of-life and sexual function changes
timeFrame: The EPIC-26 questionnaire will be completed by patients up to 24 months after prostatectomy
measure: Biochemical recurrence of prostate cancer at 2 years
timeFrame: PSA levels will be measured up to 24 months after prostatectomy
Other outcomes:
Locations:
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
Study officials:
affiliation: Hackensack Meridian Health
name: Nitin Yerram, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aalberts M, Stout TA, Stoorvogel W. Prostasomes: extracellular vesicles from the prostate. Reproduction. 2013 Nov 16;147(1):R1-14. doi: 10.1530/REP-13-0358. Print 2014 Jan.
citation: Powell IJ, Dyson G, Land S, Ruterbusch J, Bock CH, Lenk S, Herawi M, Everson R, Giroux CN, Schwartz AG, Bollig-Fischer A. Genes associated with prostate cancer are differentially expressed in African American and European American men. Cancer Epidemiol Biomarkers Prev. 2013 May;22(5):891-7. doi: 10.1158/1055-9965.EPI-12-1238. Epub 2013 Mar 20.
citation: Attard G, Murphy L, Clarke NW, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Amos CL, Atako N, Pugh C, Buckner M, Chowdhury S, Malik Z, Russell JM, Gilson C, Rush H, Bowen J, Lydon A, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzoueb M, Parikh O, Robinson A, Syndikus I, Wylie J, Zarkar A, Thalmann G, de Bono JS, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022 Jan 29;399(10323):447-460. doi: 10.1016/S0140-6736(21)02437-5. Epub 2021 Dec 23.
citation: Bebelman MP, Janssen E, Pegtel DM, Crudden C. The forces driving cancer extracellular vesicle secretion. Neoplasia. 2021 Jan;23(1):149-157. doi: 10.1016/j.neo.2020.11.011. Epub 2020 Dec 14.
citation: Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis. Cancer Cell. 2016 Dec 12;30(6):836-848. doi: 10.1016/j.ccell.2016.10.009.
citation: Carlsson L, Pahlson C, Bergquist M, Ronquist G, Stridsberg M. Antibacterial activity of human prostasomes. Prostate. 2000 Sep 1;44(4):279-86. doi: 10.1002/1097-0045(20000901)44:43.0.co;2-2.
citation: Cooperberg MR, Cowan J, Broering JM, Carroll PR. High-risk prostate cancer in the United States, 1990-2007. World J Urol. 2008 Jun;26(3):211-8. doi: 10.1007/s00345-008-0250-7. Epub 2008 Mar 28.
citation: D'Amico AV, Whittington R, Malkowicz SB, Fondurulia J, Chen MH, Kaplan I, Beard CJ, Tomaszewski JE, Renshaw AA, Wein A, Coleman CN. Pretreatment nomogram for prostate-specific antigen recurrence after radical prostatectomy or external-beam radiation therapy for clinically localized prostate cancer. J Clin Oncol. 1999 Jan;17(1):168-72. doi: 10.1200/JCO.1999.17.1.168.
citation: D'Amico AV, Whittington R, Malkowicz SB, Fondurulia J, Chen MH, Tomaszewski JE, Wein A. The combination of preoperative prostate specific antigen and postoperative pathological findings to predict prostate specific antigen outcome in clinically localized prostate cancer. J Urol. 1998 Dec;160(6 Pt 1):2096-101. doi: 10.1097/00005392-199812010-00041.
citation: D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998 Sep 16;280(11):969-74. doi: 10.1001/jama.280.11.969.
citation: Eapen RS, Buteau JP, Jackson P, Mitchell C, Oon SF, Alghazo O, McIntosh L, Dhiantravan N, Scalzo MJ, O'Brien J, Sandhu S, Azad AA, Williams SG, Sharma G, Haskali MB, Bressel M, Chen K, Jenjitranant P, McVey A, Moon D, Lawrentschuk N, Neeson PJ, Murphy DG, Hofman MS. Administering [177Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study. Eur Urol. 2024 Mar;85(3):217-226. doi: 10.1016/j.eururo.2023.08.026. Epub 2023 Oct 26.
citation: Fabiani R, Johansson L, Lundkvist O, Ronquist G. Enhanced recruitment of motile spermatozoa by prostasome inclusion in swim-up medium. Hum Reprod. 1994 Aug;9(8):1485-9. doi: 10.1093/oxfordjournals.humrep.a138735.
citation: Gafita A, Djaileb L, Rauscher I, Fendler WP, Hadaschik B, Rowe SP, Herrmann K, Calais J, Rettig M, Eiber M, Weber M, Benz MR, Farolfi A. Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0) in Metastatic Castration-resistant Prostate Cancer. Radiology. 2023 Jul;308(1):e222148. doi: 10.1148/radiol.222148.
citation: Gafita A, Rauscher I, Weber M, Hadaschik B, Wang H, Armstrong WR, Tauber R, Grogan TR, Czernin J, Rettig MB, Herrmann K, Calais J, Weber WA, Benz MR, Fendler WP, Eiber M. Novel Framework for Treatment Response Evaluation Using PSMA PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer (RECIP 1.0): An International Multicenter Study. J Nucl Med. 2022 Nov;63(11):1651-1658. doi: 10.2967/jnumed.121.263072. Epub 2022 Apr 14.
citation: Ginini L, Billan S, Fridman E, Gil Z. Insight into Extracellular Vesicle-Cell Communication: From Cell Recognition to Intracellular Fate. Cells. 2022 Apr 19;11(9):1375. doi: 10.3390/cells11091375.
citation: Ham WS, Chalfin HJ, Feng Z, Trock BJ, Epstein JI, Cheung C, Humphreys E, Partin AW, Han M. New Prostate Cancer Grading System Predicts Long-term Survival Following Surgery for Gleason Score 8-10 Prostate Cancer. Eur Urol. 2017 Jun;71(6):907-912. doi: 10.1016/j.eururo.2016.11.006. Epub 2016 Nov 19.
citation: Jackson W, Hamstra DA, Johnson S, Zhou J, Foster B, Foster C, Li D, Song Y, Palapattu GS, Kunju LP, Mehra R, Feng FY. Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer-specific death in patients receiving salvage radiation therapy following radical prostatectomy. Cancer. 2013 Sep 15;119(18):3287-94. doi: 10.1002/cncr.28215. Epub 2013 Jul 2.
citation: Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020 Feb 7;367(6478):eaau6977. doi: 10.1126/science.aau6977.
citation: Kumar S, Shelley M, Harrison C, Coles B, Wilt TJ, Mason MD. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database Syst Rev. 2006 Oct 18;2006(4):CD006019. doi: 10.1002/14651858.CD006019.pub2.
citation: Loeb S, Schaeffer EM, Trock BJ, Epstein JI, Humphreys EB, Walsh PC. What are the outcomes of radical prostatectomy for high-risk prostate cancer? Urology. 2010 Sep;76(3):710-4. doi: 10.1016/j.urology.2009.09.014. Epub 2009 Nov 22.
citation: Manouchehri Doulabi E, Fredolini C, Gallini R, Lof L, Shen Q, Ikebuchi R, Dubois L, Azimi A, Loudig O, Gabrielsson S, Landegren U, Larsson A, Bergquist J, Kamali-Moghaddam M. Surface protein profiling of prostate-derived extracellular vesicles by mass spectrometry and proximity assays. Commun Biol. 2022 Dec 22;5(1):1402. doi: 10.1038/s42003-022-04349-x.
citation: Minelli A, Ronquist G, Carlsson L, Mearini E, Nilsson O, Larsson A. Antiprostasome antibody titres in benign and malignant prostate disease. Anticancer Res. 2005 Nov-Dec;25(6C):4399-402.
citation: Mitchell MI, Ben-Dov IZ, Liu C, Ye K, Chow K, Kramer Y, Gangadharan A, Park S, Fitzgerald S, Ramnauth A, Perlin DS, Donato M, Bhoy E, Manouchehri Doulabi E, Poulos M, Kamali-Moghaddam M, Loudig O. Extracellular Vesicle Capture by AnTibody of CHoice and Enzymatic Release (EV-CATCHER): A customizable purification assay designed for small-RNA biomarker identification and evaluation of circulating small-EVs. J Extracell Vesicles. 2021 Jun;10(8):e12110. doi: 10.1002/jev2.12110. Epub 2021 Jun 3.
citation: Mitchell JA, Cooperberg MR, Elkin EP, Lubeck DP, Mehta SS, Kane CJ, Carroll PR. Ability of 2 pretreatment risk assessment methods to predict prostate cancer recurrence after radical prostatectomy: data from CaPSURE. J Urol. 2005 Apr;173(4):1126-31. doi: 10.1097/01.ju.0000155535.25971.de.
citation: Schaeffer EM, Srinivas S, Adra N, An Y, Barocas D, Bitting R, Bryce A, Chapin B, Cheng HH, D'Amico AV, Desai N, Dorff T, Eastham JA, Farrington TA, Gao X, Gupta S, Guzzo T, Ippolito JE, Kuettel MR, Lang JM, Lotan T, McKay RR, Morgan T, Netto G, Pow-Sang JM, Reiter R, Roach M, Robin T, Rosenfeld S, Shabsigh A, Spratt D, Teply BA, Tward J, Valicenti R, Wong JK, Berardi RA, Shead DA, Freedman-Cass DA. NCCN Guidelines(R) Insights: Prostate Cancer, Version 1.2023. J Natl Compr Canc Netw. 2022 Dec;20(12):1288-1298. doi: 10.6004/jnccn.2022.0063.
citation: Narang AK, Gergis C, Robertson SP, He P, Ram AN, McNutt TR, Griffith E, DeWeese TA, Honig S, Singh H, Song DY, Tran PT, DeWeese TL. Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation. Int J Radiat Oncol Biol Phys. 2016 Feb 1;94(2):254-62. doi: 10.1016/j.ijrobp.2015.10.056. Epub 2015 Oct 31.
citation: Pluvicto (lutetium lu 177 vipivotide tetraxetan) [prescribing information]. Millburn, NJ: Advanced Accelerator Applications USA Inc; October 2022.
citation: Pluvicto (lutetium lu 177 vipivotide tetraxetan) [product monograph]. Millburn, NJ: Advanced Accelerator Applications USA Inc; August 2022.
citation: Poliakov A, Spilman M, Dokland T, Amling CL, Mobley JA. Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen. Prostate. 2009 Feb 1;69(2):159-67. doi: 10.1002/pros.20860.
citation: Ronquist G, Nilsson BO. The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth. Prostate Cancer Prostatic Dis. 2004;7(1):21-31. doi: 10.1038/sj.pcan.4500684.
citation: Saez F, Motta C, Boucher D, Grizard G. Antioxidant capacity of prostasomes in human semen. Mol Hum Reprod. 1998 Jul;4(7):667-72. doi: 10.1093/molehr/4.7.667.
citation: Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Armour A, Perez-Contreras WJ, DeSilvio M, Kpamegan E, Gericke G, Messmann RA, Morris MJ, Krause BJ; VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103. doi: 10.1056/NEJMoa2107322. Epub 2021 Jun 23.
citation: Schulman CC, Debruyne FM, Forster G, Selvaggi FP, Zlotta AR, Witjes WP. 4-Year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer. Eur Urol. 2000 Dec;38(6):706-13. doi: 10.1159/000020366.
citation: Skibinski G, Kelly RW, Harkiss D, James K. Immunosuppression by human seminal plasma--extracellular organelles (prostasomes) modulate activity of phagocytic cells. Am J Reprod Immunol. 1992 Sep;28(2):97-103. doi: 10.1111/j.1600-0897.1992.tb00767.x.
citation: Spahn M, Joniau S, Gontero P, Fieuws S, Marchioro G, Tombal B, Kneitz B, Hsu CY, Van Der Eeckt K, Bader P, Frohneberg D, Tizzani A, Van Poppel H. Outcome predictors of radical prostatectomy in patients with prostate-specific antigen greater than 20 ng/ml: a European multi-institutional study of 712 patients. Eur Urol. 2010 Jul;58(1):1-7; discussion 10-1. doi: 10.1016/j.eururo.2010.03.001. Epub 2010 Mar 17.
citation: Sundi D, Tosoian JJ, Nyame YA, Alam R, Achim M, Reichard CA, Li J, Wilkins L, Schwen Z, Han M, Davis JW, Klein EA, Schaeffer EM, Stephenson AJ, Ross AE, Chapin BF. Outcomes of very high-risk prostate cancer after radical prostatectomy: Validation study from 3 centers. Cancer. 2019 Feb 1;125(3):391-397. doi: 10.1002/cncr.31833. Epub 2018 Nov 13.
citation: Sundi D, Wang VM, Pierorazio PM, Han M, Bivalacqua TJ, Ball MW, Antonarakis ES, Partin AW, Schaeffer EM, Ross AE. Very-high-risk localized prostate cancer: definition and outcomes. Prostate Cancer Prostatic Dis. 2014 Mar;17(1):57-63. doi: 10.1038/pcan.2013.46. Epub 2013 Nov 5.
citation: Tan M, Xiong X. Continuous and group sequential conditional probability ratio tests for phase II clinical trials. Stat Med. 1996 Oct 15;15(19):2037-51. doi: 10.1002/(SICI)1097-0258(19961015)15:193.0.CO;2-Z.
citation: Tan MT, Xiong X. A flexible multi-stage design for phase II oncology trials. Pharm Stat. 2011 Jul-Aug;10(4):369-73. doi: 10.1002/pst.478. Epub 2010 Dec 8.
citation: Tavoosidana G, Ronquist G, Darmanis S, Yan J, Carlsson L, Wu D, Conze T, Ek P, Semjonow A, Eltze E, Larsson A, Landegren UD, Kamali-Moghaddam M. Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8809-14. doi: 10.1073/pnas.1019330108. Epub 2011 May 9.
citation: Vickram S, Rohini K, Anbarasu K, Dey N, Jeyanthi P, Thanigaivel S, Issac PK, Arockiaraj J. Semenogelin, a coagulum macromolecule monitoring factor involved in the first step of fertilization: A prospective review. Int J Biol Macromol. 2022 Jun 1;209(Pt A):951-962. doi: 10.1016/j.ijbiomac.2022.04.079. Epub 2022 Apr 18.
citation: Yang C, Guo WB, Zhang WS, Bian J, Yang JK, Zhou QZ, Chen MK, Peng W, Qi T, Wang CY, Liu CD. Comprehensive proteomics analysis of exosomes derived from human seminal plasma. Andrology. 2017 Sep;5(5):1007-1015. doi: 10.1111/andr.12412.
citation: Yu W, Hurley J, Roberts D, Chakrabortty SK, Enderle D, Noerholm M, Breakefield XO, Skog JK. Exosome-based liquid biopsies in cancer: opportunities and challenges. Ann Oncol. 2021 Apr;32(4):466-477. doi: 10.1016/j.annonc.2021.01.074. Epub 2021 Feb 4.
citation: Zagars GK, Pollack A, von Eschenbach AC. Prognostic factors for clinically localized prostate carcinoma: analysis of 938 patients irradiated in the prostate specific antigen era. Cancer. 1997 Apr 1;79(7):1370-80.