Focal Therapy and the Index Lesion Hypothesis in Prostate Cancer

  • Mitchell Kamrava
  • Patrick Kupelian
Part of the Medical Radiology book series (MEDRAD)


Standard whole gland radiation therapy for prostate cancer results in high cure rates but impacts quality of life. Active surveillance is an alternative but has not been widely embraced. Focal therapy represents a middle ground between these two treatment options. In this paper we will review the rationale, patient selection considerations, technical planning issues, and recent clinical data for prostate focal therapy.


Prostate Cancer Gleason Score Active Surveillance Index Lesion Focal Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Ahmed HU (2009) The index lesion and the origin of prostate cancer. N Engl J Med 361(17):1704–1706PubMedCrossRefGoogle Scholar
  2. Ahmed HU et al (2011) Focal therapy for localized prostate cancer: a phase I/II trial. J Urol 185(4):1246–1255PubMedCrossRefGoogle Scholar
  3. Ahmed HU et al (2012) Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study. Lancet Oncol 13(6):622–632PubMedCentralPubMedCrossRefGoogle Scholar
  4. Arakawa A et al (1995) High grade prostatic intraepithelial neoplasia in prostates removed following irradiation failure in the treatment of prostatic adenocarcinoma. Pathol Res Pract 191(9):868–872PubMedCrossRefGoogle Scholar
  5. Arrayeh E et al (2012) Does local recurrence of prostate cancer after radiation therapy occur at the site of primary tumor? Results of a longitudinal MRI and MRSI study. Int J Radiat Oncol Biol Physics 82(5):787–e793Google Scholar
  6. Bastian PJ et al (2004) Characteristics of insignificant clinical T1c prostate tumors. Cancer 101(9):2001–2005PubMedCrossRefGoogle Scholar
  7. Bostwick DG et al (2007) Group consensus reports from the consensus conference on focal treatment of prostatic carcinoma, celebration, florida, February 24, 2006. Urology 70(6, Supplement 1):S42–S44Google Scholar
  8. Bozzini G et al (2013) Focal therapy of prostate cancer: energies and procedures. Urol Oncol Semin Original Invest 31:155–167Google Scholar
  9. Bott SRJ et al (2010) The index lesion and focal therapy: an analysis of the pathological characteristics of prostate cancer. BJU International 106(11):1607–1611PubMedCrossRefGoogle Scholar
  10. Cellini N et al (2002) Analysis of intraprostatic failures in patients treated with hormonal therapy and radiotherapy: implications for conformal therapy planning. Int J Radiat Oncol Biol Physics 53(3):595–599Google Scholar
  11. Cheng L et al (1999) Prevalence and distribution of prostatic Intraepithelial neoplasia in Salvage radical prostatectomy specimens after radiation therapy. Am Jo Surg Pathol 23(7):803CrossRefGoogle Scholar
  12. Chun FKH et al (2008) Critical assessment of tools to predict clinically insignificant prostate cancer at radical prostatectomy in contemporary men. Cancer 113(4):701–709PubMedCrossRefGoogle Scholar
  13. Djavan BSM, Bursa B, Basharkhah A, Simak R, Marberger M (1999) Predictability and significance of multifocal prostate cancer in the radical prostatectomy specimen. Tech Urol 5(3):139–142PubMedCrossRefGoogle Scholar
  14. EpsteinJI CD, Sokoll LJ, Wlash PC, Cox JL, Rittenhouse H, Wolfert R, Carter HB (1998) Nonpalpable stage T1c prostate cancer: prediction of insignificant disease using free/total prostate specific antigen levels and needle biopsy findings. J Urol 160(6 Pt 2):2407–2411Google Scholar
  15. Epstein JI (2011) Prognostic significance of tumor volume in radical prostatectomy and needle biopsy specimens. J Urol 186(3):790–797PubMedCrossRefGoogle Scholar
  16. Epstein Ji WPCCMBCB (1994) PAthologic and clinical findings to predict tumor extent of nonpalpable (stage t1 c) prostate cancer. J Am Med Assoc 271(5):368–374CrossRefGoogle Scholar
  17. Fedorov A et al (2012) Image registration for targeted MRI-guided transperineal prostate biopsy. J Magn Reson Imaging 36(4):987–992PubMedCentralPubMedCrossRefGoogle Scholar
  18. Gburek BM et al (1997) Chromosomal anomalies in stage D1 prostate adenocarcinoma primary tumors and lymph node metastases detected by Fluorescence in situ hybridization. J Urol 157(1):223–227PubMedCrossRefGoogle Scholar
  19. Groenendaal G et al (2012) The effect of hormonal treatment on conspicuity of prostate cancer: implications for focal boosting radiotherapy. Radiother Oncol 103(2):233–238PubMedCrossRefGoogle Scholar
  20. Grimm P et al (2012) Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the prostate cancer results study group. BJU International 109:22–29PubMedCrossRefGoogle Scholar
  21. Hu Y et al (2012a) 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 110(6):812–820PubMedCrossRefGoogle Scholar
  22. Hu Y et al (2012b) MR to ultrasound registration for image-guided prostate interventions. Med Image Anal 16(3):687–703PubMedCrossRefGoogle Scholar
  23. Kamrava M C.M, Kayode O, Wang J, Marks L, Kupelian P, Steinberg M, Park S, Demanes D (2013) Focal high-dose-rate brachytherapy: a dosimetric comparison of hemi-gland versus conventional whole-gland treatment brachytherapy. Brachytherapy 86(5):819–821Google Scholar
  24. Kamrava M, M.S, Banergee R, Raman S, Marks L, Demanes D, Margolis D (2013) Evaluating the utility of a multi-parametric MRI based cancer suspicion score in defining brachytherapy focal therapy targets for prostate cancer. In: Proceedings of the American Brachytherapy society 2013 Annual MeetingGoogle Scholar
  25. Karavitakis M et al (2011) Histological characteristics of the index lesion in whole-mount radical prostatectomy specimens: implications for focal therapy. Prostate Cancer Prostatic Dis 14(1):46–52PubMedCrossRefGoogle Scholar
  26. Karavitakis M, Ahmed HU, Abel PD, Hazell S, Winkler MH (2012) Anatomically versus biologically unifocal prostate cancer: a pathological evaluation in the context of focal therapy. Ther Adv Urol 4(4):155–160PubMedCentralPubMedCrossRefGoogle Scholar
  27. Kasivisvanathan V et al (2013) Transperineal magnetic resonance image targeted prostate biopsy versus transperineal template prostate biopsy in the detection of clinically significant prostate cancer. J Urology 189(3):860–866Google Scholar
  28. Klotz L et al (2010) Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 28(1):126–131PubMedCrossRefGoogle Scholar
  29. Langley S et al (2012) Report of a consensus meeting on focal low dose rate brachytherapy for prostate cancer. BJU Int 109:7–16PubMedCrossRefGoogle Scholar
  30. Lecornet E et al (2012) The accuracy of different biopsy strategies for the detection of clinically important prostate cancer: a computer simulation. J Urol 188(3):974–980PubMedCrossRefGoogle Scholar
  31. Liu W et al (2009) Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat Med 15(5):559–565PubMedCentralPubMedCrossRefGoogle Scholar
  32. Makarov DV et al (2007) Updated nomogram to predict pathologic stage of prostate cancer given prostate-specific antigen level, clinical stage, and biopsy gleason score (partin tables) based on cases from 2000 to 2005. Urology 69(6):1095–1101PubMedCentralPubMedCrossRefGoogle Scholar
  33. Matsuoka Y et al (2012) Combination of diffusion-weighted magnetic resonance imaging and extended prostate biopsy predicts lobes without significant cancer: application in patient selection for hemiablative focal therapy. Eur Urol Oct 16. pii: S0302-2838(12)01229-8Google Scholar
  34. Mehra R et al (2008) Characterization of TMPRSS2-ETS gene aberrations in androgen-independent metastatic prostate cancer. Cancer Res 68(10):3584–3590PubMedCentralPubMedCrossRefGoogle Scholar
  35. Miller GJ, Cygan JM (1994) Morphology of prostate cancer: the effects of multifocality on histological grade, tumor volume and cpsule penetration. J Urol 152(5 Pt 2):1709–1713Google Scholar
  36. Mouraviev V et al (2007) Prostate cancer laterality as a rationale of focal ablative therapy for the treatment of clinically localized prostate cancer. Cancer 110(4):906–910PubMedCrossRefGoogle Scholar
  37. Nakanishi H et al (2007) A nomogram for predicting low-volume/low-grade prostate cancer. Cancer 110(11):2441–2447PubMedCrossRefGoogle Scholar
  38. Nguyen PL et al (2012) Updated results of magnetic resonance imaging guided partial prostate brachytherapy for favorable risk prostate cancer: implications for focal therapy. J Urol 188(4):1151–1156PubMedCentralPubMedCrossRefGoogle Scholar
  39. Noguchi M et al (2001) Relationship between systematic biopsies and histological features of 222 radical prostatectomy specimens: lack of prediction of tumor significance for men with nonpalpable prostate cancer. J Urol 166(1):104–110PubMedCrossRefGoogle Scholar
  40. Onik G, Miessau M, Bostwick DG (2009) Three-dimensional prostate mapping biopsy has a potentially significant impact on prostate cancer management. J Clin Oncol 27(26):4321–4326PubMedCrossRefGoogle Scholar
  41. Ploussard G et al (2011) The contemporary concept of significant versus insignificant prostate cancer. Eur Urol 60(2):291–303PubMedCrossRefGoogle Scholar
  42. Pucar D (2007) et al., Clinically significant prostate cancer local recurrence after radiation therapy occurs at the site of primary tumor: magnetic resonance imaging and step-section pathology evidence. Int J Radiat Oncol Biol Physics 69(1):62–69Google Scholar
  43. Rice KR et al (2009) Clinicopathological behavior of single focus prostate adenocarcinoma. J Urol 182(6):2689–2694PubMedCrossRefGoogle Scholar
  44. Ruijter ET et al (1996) Histological grade heterogeneity in multifocal prostate cancer. Biological and clinical implications. J Pathol 180(3):295–299PubMedCrossRefGoogle Scholar
  45. Sanda MG et al (2008) Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med 358(12):1250–1261PubMedCrossRefGoogle Scholar
  46. Schmidt H et al (2006) Asynchronous growth of prostate cancer is reflected by circulating tumor cells delivered from distinct, even SMALL foci, harboring loss of heterozygosity of the PTEN gene. Cancer Res 66(18):8959–8965PubMedCrossRefGoogle Scholar
  47. Sonn GA et al (2013) Targeted biopsy in the detection of prostate cancer using an office based magnetic resonance ultrasound fusion device. J Urol 189(1):86–92PubMedCentralPubMedCrossRefGoogle Scholar
  48. Stamey Ta FF McNeal JE, Redwine EA, Whittermore AS, Schmid H (1993) Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer 71(S3):993–938Google Scholar
  49. Stamey Ta MJEYCMSBMJIM (1999) BIological determinants of cancer progression in men with prostate cancer.J Am Med Assoc 281(15):1395–1400Google Scholar
  50. Tareen B et al (2009) Appropriate candidates for hemiablative focal therapy are infrequently encountered among men selected for radical prostatectomy in contemporary cohort. Urology 73(2):351–354PubMedCrossRefGoogle Scholar
  51. Trpkov K et al (2010) ‘Insignificant’ prostate cancer on prostatectomy and cystoprostatectomy: variation on a theme ‘low-volume/low-grade’ prostate cancer? BJU Int 106(3):304–315PubMedCrossRefGoogle Scholar
  52. Tsivian M et al (2010) Predicting unilateral prostate cancer on routine diagnostic biopsy: sextant versus extended. BJU International 105(8):1089–1092PubMedCrossRefGoogle Scholar
  53. Turkbey B et al (2011) Multiparametric 3T prostate magnetic resonance imaging to detect cancer: histopathological correlation using prostatectomy specimens processed in customized magnetic resonance imaging based molds. J Urol 186(5):1818–1824PubMedCrossRefGoogle Scholar
  54. Turkbey B et al (2012) Correlation of magnetic resonance imaging tumor volume with histopathology. J Urol 188(4):1157–1163PubMedCrossRefGoogle Scholar
  55. Vainshtein J, A.-I.E., Olson KB, Ray ME, Sandler HM, Normolle D, Litzenberg DW, Masi K, Pan C, Hamstra DA (2012) Randomized phase II trial of urethral sparing intensity modulated radiation therapy in low-risk prostate cancer: implications for focal therapy. Radiat Oncol 7(82)Google Scholar
  56. Villers AMJ, Freiha FS, Stamey TA (1992) Multiple cancers in the prostate. Morphologic features of clinically recognized versus incidental tumors. Cancer 70(9):2313–2318PubMedCrossRefGoogle Scholar
  57. Ward JF, Jones JS (2012) Focal cryotherapy for localized prostate cancer: a report from the national Cryo On-Line Database (COLD) registry. BJU International 109(11):1648–1654PubMedCrossRefGoogle Scholar
  58. Wilt TJ et al (2012) Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 367(3):203–213PubMedCentralPubMedCrossRefGoogle Scholar
  59. Wise AM et al (2002) Morphologic and clinical significance of multifocal prostate cancers in radical prostatectomy specimens. Urology 60(2):264–269PubMedCrossRefGoogle Scholar
  60. Yamada Y et al (2012) American Brachytherapy Society consensus guidelines for high-dose-rate prostate brachytherapy. Brachytherapy 11(1):20–32PubMedCrossRefGoogle Scholar
  61. Yerram NK et al (2012) Low suspicion lesions on multiparametric magnetic resonance imaging predict for the absence of high-risk prostate cancer. BJU Int 110(11 Pt B):E783–E788 Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Radiation OncologyUniversity of California Los AngelesLos AngelesUS

Personalised recommendations