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Understanding the diagnosis of prostate cancer

Xuan Rui S Ong, Dominic Bagguley, John W Yaxley, Arun A Azad, Declan G Murphy and Nathan Lawrentschuk
Med J Aust 2020; 213 (9): . || doi: 10.5694/mja2.50820
Published online: 2 November 2020

Summary

  • Prostate cancer continues to be the most commonly diagnosed cancer, and the second leading cause of cancer death among Australian men.
  • Prostate‐specific antigen testing is personalised (not dichotomous in nature) and its interpretation should take into account the patient's age, symptoms, previous results and medication (eg, 5‐α reductase inhibitors such as dutasteride).
  • Multiparametric magnetic resonance imaging of the prostate has been proven to have a 93% sensitivity for detecting clinically significant prostate cancer. It has the potential to decrease unnecessary prostate biopsies by around 27%.
  • International Society of Urological Pathology (ISUP) grade 1 (Gleason score 6) has been shown to have very little, if any, risk of metastasis
  • ISUP grade 1 (Gleason score 3 +3 = 6) and low percentage ISUP grade 2 (Gleason score 3 + 4 [< 10%] = 7) can be offered active surveillance. The goal of active surveillance is to defer treatment but is still curative when required.
  • With better imaging (magnetic resonance imaging and emerging prostate‐specific membrane antigen positron emission tomography–computed tomography) and transperineal prostate biopsy, more men can be offered screening after discussion of risks and benefits, knowing that overdiagnosis has been minimised and radical treatment is reserved for only the most aggressive disease.

  • 1 EJ Whitten Prostate Cancer Research Centre at Epworth, Melbourne, VIC
  • 2 University of Melbourne, Melbourne, VIC
  • 3 University of Queensland, Brisbane, QLD
  • 4 Royal Brisbane and Women's Hospital, Brisbane, QLD
  • 5 Peter MacCallum Cancer Centre, Melbourne, VIC


Correspondence: lawrentschuk@gmail.com

Competing interests:

No relevant disclosures.

  • 1. Roberts MJ, Papa N, Perera M, et al. A contemporary, nationwide analysis of surgery and radiotherapy treatment for prostate cancer. BJU Int 2019; 124 (Suppl 1): 31–36.
  • 2. Australian Institute of Health and Welfare. Cancer in Australia 2019 (Cancer Series No. 119; Cat. No. CAN 123). Canberra: AIHW, 2019. https://www.aihw.gov.au/getmedia/8c9fcf52-0055-41a0-96d9-f81b0feb98cf/aihw-can-123.pdf.aspx?inline=true (viewed Aug 2020).
  • 3. Wang MC, Valenzuela LA, Murphy GP, Chu TM. Purification of a human prostate specific antigen. J Urol 2017; 197 (2 Suppl): S148–S152.
  • 4. Stamey TA, Yang N, Hay AR, et al. Prostate‐specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987; 317: 909–916.
  • 5. Lilja H, Ulmert D, Vickers AJ. Prostate‐specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer 2008; 8: 268–278.
  • 6. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate‐specific antigen level < or =4.0 ng per milliliter. N Engl J Med 2004; 350: 2239–2246.
  • 7. Loeb S, Roehl KA, Antenor JA, et al. Baseline prostate‐specific antigen compared with median prostate‐specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old. Urology 2006; 67: 316–320.
  • 8. Litchfield MJ, Cumming RG, Smith DP, et al. Prostate‐specific antigen levels in men aged 70 years and over: findings from the CHAMP study. Med J Aust 2012; 196: 395–398. https://www.mja.com.au/journal/2012/196/6/prostate-specific-antigen-levels-men-aged-70-years-and-over-findings-champ-study.
  • 9. Oesterling JE, Jacobsen SJ, Chute CG, et al. Serum prostate‐specific antigen in a community‐based population of healthy men. Establishment of age‐specific reference ranges. JAMA 1993; 270: 860–864.
  • 10. Morgan TO, Jacobsen SJ, McCarthy WF, et al. Age‐specific reference ranges for serum prostate‐specific antigen in black men. N Engl J Med 1996; 335: 304–310.
  • 11. Partin AW, Criley SR, Subong EN, et al. Standard versus age‐specific prostate specific antigen reference ranges among men with clinically localized prostate cancer: a pathological analysis. J Urol 1996; 155: 1336–1339.
  • 12. DeAntoni EP, Crawford ED, Oesterling JE, et al. Age‐ and race‐specific reference ranges for prostate‐specific antigen from a large community‐based study. Urology 1996; 48: 234–239.
  • 13. Anderson JR, Strickland D, Corbin D, et al. Age‐specific reference ranges for serum prostate‐specific antigen. Urology 1995; 46: 54–57.
  • 14. Oesterling JE, Jacobsen SJ, Klee GG, et al. Free, complexed and total serum prostate specific antigen: the establishment of appropriate reference ranges for their concentrations and ratios. J Urol 1995; 154: 1090–1095.
  • 15. Borer JG, Sherman J, Solomon MC, et al. Age specific prostate specific antigen reference ranges: population specific. J Urol 1998; 159: 444–448.
  • 16. D'Amico AV, Roehrborn CG. Effect of 1 mg/day finasteride on concentrations of serum prostate‐specific antigen in men with androgenic alopecia: a randomised controlled trial. Lancet Oncol 2007; 8: 21–25.
  • 17. Marks LS, Andriole GL, Fitzpatrick JM, et al. The interpretation of serum prostate specific antigen in men receiving 5alpha‐reductase inhibitors: a review and clinical recommendations. J Urol 2006; 176: 868–74.
  • 18. Marks LS, Andriole GL, Fitzpatrick JM, et al. The interpretation of serum prostate specific antigen in men receiving 5α‐reductase inhibitors: a review and clinical recommendations. J Urol 2006; 176: 868–874.
  • 19. Thompson IM, Chi C, Ankerst DP, et al. Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. J Natl Cancer Inst 2006; 98: 1128–1133.
  • 20. Helfand BT, Anderson CB, Fought A, et al. Postoperative PSA and PSA velocity identify presence of prostate cancer after various surgical interventions for benign prostatic hyperplasia. Urology 2009; 74: 177–183.
  • 21. Nadler RB, Humphrey PA, Smith DS, et al. Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels. J Urol 1995; 154 (2 Pt 1): 407–413.
  • 22. Neal DE, Jr., Clejan S, Sarma D, Moon TD. Prostate specific antigen and prostatitis. I. Effect of prostatitis on serum PSA in the human and nonhuman primate. Prostate 1992; 20: 105–111.
  • 23. Washino S, Okochi T, Saito K, et al. Combination of prostate imaging reporting and data system (PI‐RADS) score and prostate‐specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients. BJU Int 2017; 119: 225–233.
  • 24. Vickers AJ, Brewster SF. PSA velocity and doubling time in diagnosis and prognosis of prostate cancer. Br J Med Surg Urol 2012; 5: 162–168.
  • 25. Pannek J, Rittenhouse HG, Chan DW, et al. The use of percent free prostate specific antigen for staging clinically localized prostate cancer. J Urol 1998; 159: 1238–1242.
  • 26. Catalona WJ, Partin AW, Slawin KM, et al. Use of the percentage of free prostate‐specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA 1998; 279: 1542–1547.
  • 27. Catalona WJ, Partin AW, Sanda MG, et al. A multicenter study of [‐2] pro‐prostate specific antigen combined with prostate specific antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/ml prostate specific antigen range. J Urol 2011; 185: 1650–1655.
  • 28. Vickers AJ, Cronin AM, Aus G, et al. A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden. BMC Med 2008; 6: 19.
  • 29. Russo GI, Regis F, Castelli T, et al. A systematic review and meta‐analysis of the diagnostic accuracy of Prostate Health Index and 4‐kallikrein panel score in predicting overall and high‐grade prostate cancer. Clin Genitourin Cancer 2017; 15: 429–439.e1.
  • 30. Mottet N, van den Bergh R, Briers E. EAU‐EANM-ESTRO‐ESUR-SIOG guidelines on prostate cancer. Eur Urol 2019; 75: 889–890.
  • 31. Grossman DC, Curry SJ, Owens DK, et al. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA 2018; 319: 1901–1913.
  • 32. Prostate Cancer Foundation of Australia and Cancer Council Australia. Clinical practice guidelines for PSA testing and early management of test‐detected prostate cancer. 2015. https://wiki.cancer.org.au/australia/Guidelines:PSA_Testing (viewed Aug 2020).
  • 33. Catalona WJ, Richie JP, Ahmann FR, et al. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men. J Urol 2017; 197 (2 Suppl): S200–S207.
  • 34. Patel MI, Kakala B, Beattie K. Teaching medical students digital rectal examination: a randomized study of simulated model vs rectal examination volunteers. BJU Int 2019; 124 (Suppl 1): 14–18.
  • 35. Schröder FH, Kruger AB, Rietbergen J, et al. Evaluation of the digital rectal examination as a screening test for prostate cancer. J Natl Cancer Inst 1998; 90: 1817–1823.
  • 36. Carvalhal GF, Smith DS, Mager DE, et al. Digital rectal examination for detecting prostate cancer at prostate specific antigen levels of 4 ng/ml or less. J Urol 1999; 161: 835–839.
  • 37. Thompson J, Van Leeuwen P, Moses D, et al. The diagnostic performance of multiparametric magnetic resonance imaging to detect significant prostate cancer. J Urol 2016; 195: 1428–1435.
  • 38. Ahmed HU, El‐Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi‐parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 2017; 389: 815–822.
  • 39. Hu Y, Ahmed HU, Carter T, et al. A biopsy simulation study to assess the accuracy of several transrectal ultrasonography (TRUS)‐biopsy strategies compared with template prostate mapping biopsies in patients who have undergone radical prostatectomy. BJU Int 2012; 110: 812–820.
  • 40. Norberg M, Egevad L, Holmberg L, et al. The sextant protocol for ultrasound‐guided core biopsies of the prostate underestimates the presence of cancer. Urology 1997; 50: 562–566.
  • 41. Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI‐targeted or standard biopsy for prostate‐cancer diagnosis. N Engl J Med 2018; 378: 1767–1777.
  • 42. Weinreb JC, Barentsz JO, Choyke PL, et al. PI‐RADS prostate imaging ‐ reporting and data system: 2015, version 2. Eur Urol 2016; 69: 16–40.
  • 43. Park SY, Jung DC, Oh YT, et al. Prostate cancer: PI‐RADS version 2 helps preoperatively predict clinically significant cancers. Radiology 2016; 280: 108–116.
  • 44. Padhani AR, Weinreb J, Rosenkrantz AB, et al. Prostate Imaging‐Reporting and Data System Steering Committee: PI‐RADS v2 status update and future directions. Eur Urol 2019; 75: 385–396.
  • 45. Woo S, Kim SY, Lee J, et al. PI‐RADS version 2 for prediction of pathological downgrading after radical prostatectomy: a preliminary study in patients with biopsy‐proven Gleason Score 7 (3+4) prostate cancer. Eur Radiol 2016; 26: 3580–3587.
  • 46. Hansen NL, Barrett T, Kesch C, et al. Multicentre evaluation of magnetic resonance imaging supported transperineal prostate biopsy in biopsy‐naïve men with suspicion of prostate cancer. BJU Int 2018; 122: 40–49.
  • 47. Wei TC, Lin TP, Chang YH, et al. Transrectal ultrasound‐guided prostate biopsy in Taiwan: A nationwide database study. J Chin Med Assoc 2015; 78: 662–665.
  • 48. Grummet JP, Weerakoon M, Huang S, et al. Sepsis and ‘superbugs’: should we favour the transperineal over the transrectal approach for prostate biopsy? BJU Int 2014; 114: 384–388.
  • 49. Symons JL, Huo A, Yuen CL, et al. Outcomes of transperineal template‐guided prostate biopsy in 409 patients. BJU Int 2013; 112: 585–593.
  • 50. Yaxley AJ, Yaxley JW, Thangasamy IA, et al. Comparison between target magnetic resonance imaging (MRI) in‐gantry and cognitively directed transperineal or transrectal‐guided prostate biopsies for Prostate Imaging‐Reporting and Data System (PI‐RADS) 3‐5 MRI lesions. BJU Int 2017; 120 (Suppl 3): 43–50.
  • 51. Stefanova V, Buckley R, Flax S, et al. Transperineal prostate biopsies using local anesthesia: experience with 1,287 patients. prostate cancer detection rate, complications and patient tolerability. J Urol 2019; 201: 1121–1126.
  • 52. Grummet J, Gorin MA, Popert R, et al. “TREXIT 2020”: why the time to abandon transrectal prostate biopsy starts now. Prostate Cancer Prostatic Dis 2020; 23: 62–65.
  • 53. Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 2017; 197 (2 Suppl): S134–S139.
  • 54. Humphrey PA, Moch H, Cubilla AL, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs – Part B: prostate and bladder tumours. Eur Urol 2016; 70: 106–119.
  • 55. Epstein JI, Egevad L, Amin MB, et al. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 2016; 40: 244–252.
  • 56. Epstein JI, Zelefsky MJ, Sjoberg DD, et al. A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 2016; 69: 428–435.
  • 57. Ross AE, Marchionni L, Vuica‐Ross M, et al. Gene expression pathways of high grade localized prostate cancer. Prostate 2011; 71: 1568–1577.
  • 58. Ross HM, Kryvenko ON, Cowan JE, et al. Do adenocarcinomas of the prostate with Gleason score (GS) ≤6 have the potential to metastasize to lymph nodes? Am J Surg Pathol 2012; 36: 1346–1352.
  • 59. Amin A, Scheltema MJ, Shnier R, et al. The Magnetic Resonance Imaging in Active Surveillance (MRIAS) trial: use of baseline multiparametric magnetic resonance imaging and saturation biopsy to reduce the frequency of surveillance prostate biopsies. J Urol 2020; 203: 910–917.
  • 60. Hofman MS, Lawrentschuk N, Francis RJ, et al. Prostate‐specific membrane antigen PET‐CT in patients with high‐risk prostate cancer before curative‐intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet 2020; 395: 1208–1216.
  • 61. Kalapara AA, Nzenza T, Pan HYC, et al. Detection and localisation of primary prostate cancer using (68) gallium prostate‐specific membrane antigen positron emission tomography/computed tomography compared with multiparametric magnetic resonance imaging and radical prostatectomy specimen pathology. BJU Int 2020; 126: 83–90.
  • 62. Scheltema MJ, Chang JI, Stricker PD, et al. Diagnostic accuracy of 68Ga‐prostate‐specific membrane antigen (PSMA) positron‐emission tomography (PET) and multiparametric (mp) MRI to detect intermediate‐grade intra‐prostatic prostate cancer using whole‐mount pathology: impact of the addition of 68Ga‐PSMA PET to mp MRI. BJU Int 2019; 124: 42–49.
  • 63. Donato P, Morton A, Yaxley J, et al. (68)Ga‐PSMA PET/CT better characterises localised prostate cancer after MRI and transperineal prostate biopsy: is (68)Ga‐PSMA PET/CT guided biopsy the future? Eur J Nucl Med Mol Imaging 2020; 47: 1843–1851.
  • 64. Amin A, Blazevski A, Thompson J, et al. Protocol for the PRIMARY clinical trial, a prospective, multicentre, cross‐sectional study of the additive diagnostic value of gallium‐68 prostate‐specific membrane antigen positron‐emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer. BJU Int 2020; 125: 515–524.
  • 65. Rao K, Manya K, Azad A, et al. Uro‐oncology multidisciplinary meetings at an Australian tertiary referral centre–impact on clinical decision‐making and implications for patient inclusion. BJU Int 2014; 114: 50–54.

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