Biochemical Relapse After Primary Treatment for Prostate Cancer: Studies on Natural History and Therapeutic Considerations

After local treatment, a substantial proportion of patients with prostate cancer present with rising prostate specific antigen (PSA) serum levels as the only indication of disease activity. Evolving data derived from large databases that were predominantly retrospectively evaluated show that the natural history of these patients is quite variable. Various clinical and pathologic parameters have been shown to predict for the probability of development of distant metastasis, including the surgical Gleason score, time of PSA relapse after primary treatment, and PSA doubling time (PSADT). The PSADT appears to be the most important predictor of development of distant metastasis and prostate cancer-specific mortality. At present, no data support a standard management approach for these patients, and clinical trials pose a major challenge in view of the methodologic complexities involved. Patients and treating physicians should make major efforts to participate in clinical trials in this patient population.

If the inline PDF is not rendering correctly, you can download the PDF file here.

Correspondence: Mario Eisenberger, MD, Johns Hopkins Medical Institutions, 1650 Orleans Street, Blaustein/Bunting Cancer Research Building, Room 1M 51, Baltimore, MD 21231-1000. E-mail: eisenma@jhmi.edu
  • 1

    Jemal A, Murray T, Samuels A. Cancer statistics, 2003. CA Cancer J Clin 2003;53:526.

  • 2

    Han M, Partin AW, Piantadosi S. Era specific biochemical recurrence-free survival following radical prostatectomy for clinically localized prostate cancer. J Urol 2001;166:416419.

    • Search Google Scholar
    • Export Citation
  • 3

    Zietman AL, Coen JJ, Dallow KC. The treatment of prostate cancer by conventional radiation therapy: an analysis of long-term outcome. Int J Radiat Oncol Biol Phys 1995;32:287292.

    • Search Google Scholar
    • Export Citation
  • 4

    Kuban DA, Thames HD, Levy LB. Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era. Int J Radiat Oncol Biol Phys 2003;57:915928.

    • Search Google Scholar
    • Export Citation
  • 5

    Sylvester JE, Blasko JC, Grimm PD. Ten-year biochemical relapse-free survival after external beam radiation and brachytherapy for localized prostate cancer: the Seattle experience. Int J Radiat Oncol Biol Phys 2003;57:944952.

    • Search Google Scholar
    • Export Citation
  • 6

    Lotan Y, Roehrborn CG. Clearance rates of total prostate specific antigen (PSA) after radical prostatectomy in African-Americans and Caucasians.. Prostate Cancer Prostatic Dis 2002;5:111114.

    • Search Google Scholar
    • Export Citation
  • 7

    Haese A, Huland E, Graefen M, Hammerer P. Ultrasensitive detection of prostate specific antigen in the follow up of 422 patients after radical prostatectomy. J Urol 1999;161:12061211.

    • Search Google Scholar
    • Export Citation
  • 8

    Witherspoon LR, Lapeyrolerie T. Sensitive prostate specific antigen measurements identify men with long disease-free intervals and differentiate aggressive from indolent cancer recurrences within 2 years after radical prostatectomy. J Urol 1997;157:13221328.

    • Search Google Scholar
    • Export Citation
  • 9

    Stock RG, Stone NN, Cesaretti JA. Prostate-specific antigen bounce after prostate seed implantation for localized prostate cancer: descriptions and implications. Int J Radiat Oncol Biol Phys 2003;56:448453.

    • Search Google Scholar
    • Export Citation
  • 10

    Hanlon AL, Pinover WH, Horwitz EM, Hanks GE. Patterns and fate of PSA bouncing following 3D-CRT. Int J Radiat Oncol Biol Phys 2001;50:845849.

  • 11

    Rosser CJ, Kuban DA, Levy LB. Prostate specific antigen bounce phenomenon after external beam radiation for clinically localized prostate cancer. J Urol 2002;168:20012005.

    • Search Google Scholar
    • Export Citation
  • 12

    Critz FA, Williams WH, Benton JB. Prostate specific antigen bounce after radioactive seed implantation followed by external beam radiation for prostate cancer. J Urol 2000;163:10851089.

    • Search Google Scholar
    • Export Citation
  • 13

    Consensus statement: guidelines for PSA following radiation therapy. American Society for Therapeutic Radiology and Oncology Consensus Panel. Int J Radiat Oncol Biol Phys 1997;37:10351041.

    • Search Google Scholar
    • Export Citation
  • 14

    Pound CR, Partin AW, Eisenberger MA. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281:15911597.

    • Search Google Scholar
    • Export Citation
  • 15

    Eisenberger MA, Partin AW, Pound C. Natural history of progression of patients with biochemical (PSA) relapse following radical prostatectomy (Abstr #1527). Update Proc Am Soc of Clin Oncol ASCO 2003.

    • Search Google Scholar
    • Export Citation
  • 16

    D'Amico AV, Cote K, Loffredo M. Determinants of prostate cancer specific survival following radiation therapy during the prostate specific antigen era. J Urol 2003;170 (suppl):S42S46.

    • Search Google Scholar
    • Export Citation
  • 17

    D'Amico AV, Moul JW, Carroll PR. Surrogate end point for prostate cancer-specific mortality after radical prostatectomy or radiation therapy. J Natl Cancer Inst 2003;95: 13761383.

    • Search Google Scholar
    • Export Citation
  • 18

    Patel A, Dorey F, Franklin J, deKernion JB. Recurrence patterns after radical retropubic prostatectomy: clinical usefulness of prostate specific antigen doubling times and log slope prostate specific antigen. J Urol 1997;158:14411445.

    • Search Google Scholar
    • Export Citation
  • 19

    Zagars GK, Pollack A. Kinetics of serum prostate-specific antigen after external beam radiation for clinically localized prostate cancer. Radiother Oncol 1997;44:213221.

    • Search Google Scholar
    • Export Citation
  • 20

    Lee WR, Hanks GE, Hanlon A. Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: clinical observations. J Clin Oncol 1997;15:230238.

    • Search Google Scholar
    • Export Citation
  • 21

    D'Amico AV, Cote K, Loffredo M. Determinants of prostate cancer-specific survival after radiation therapy for patients with clinically localized prostate cancer. J Clin Oncol 2002;20:45674573.

    • Search Google Scholar
    • Export Citation
  • 22

    Cher ML, Bianco FJ Jr, Lam JS. Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy. J Urol 1998;160:13871391.

    • Search Google Scholar
    • Export Citation
  • 23

    Freitas JE, Gilvydas R, Ferry JD, Gonzalez JA. The clinical utility of prostate-specific antigen and bone scintigraphy in prostate cancer follow-up. J Nucl Med 1991;32:13871390.

    • Search Google Scholar
    • Export Citation
  • 24

    Kane CJ, Amling CL, Johnstone PA. Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy. Urology 2003;61:607611.

    • Search Google Scholar
    • Export Citation
  • 25

    Kahn D, Williams RD, Seldin DW. Radioimmunoscintigraphy with 111Indium labeled CYT-356 for the detection of occult prostate cancer recurrence. J Urol 1994;152:14901495.

    • Search Google Scholar
    • Export Citation
  • 26

    Hinkle GH, Burgers JK, Neal CE. Multicenter radioimmunoscintigraphic evaluation of patients with prostate carcinoma using indium-111 capromab pendetide. Cancer 1998;83:739747.

    • Search Google Scholar
    • Export Citation
  • 27

    Kahn D, Williams RD, Haseman MK. Radioimmunoscintigraphy with In-111-labeled capromab pendetide predicts prostate cancer response to salvage radiotherapy after failed radical prostatectomy. J Clin Oncol 1998;16:284289.

    • Search Google Scholar
    • Export Citation
  • 28

    Thomas CT, Bradshaw PT, Pollock BH. Indium-111-capromab pendetide radioimmunoscintigraphy and prognosis for durable biochemical response to salvage radiation therapy in men after failed prostatectomy. J Clin Oncol 2003;21:17151721.

    • Search Google Scholar
    • Export Citation
  • 29

    Mohideen N, Flanigan RJ, Dillehay G. Role of Prostascint scan in the assessment of patients who undergo radiotherapy for biochemical failure after radical prostectomy for prostate cancer (Abstr). J Urol 2002;167(suppl):174.

    • Search Google Scholar
    • Export Citation
  • 30

    Leventis AK, Shariat SF, Slawin KM. Local recurrence after radical prostatectomy: correlation of US features with prostatic fossa biopsy findings. Radiology 2001;219:432439.

    • Search Google Scholar
    • Export Citation
  • 31

    Foster LS, Jajodia P, Fournier GS. The value of prostate-specific antigen and transrectal ultrasound guided biopsy in detecting prostatic fossa recurrences following radical prostatectomy. J Urol 1993;149:10241028.

    • Search Google Scholar
    • Export Citation
  • 32

    Silverman JM, Krebs TL. MR imaging evaluation with a transrectal surface coil of local recurrence of prostatic cancer in men who have undergone radical prostatectomy. AJR Am J Roentgenol 1997;168:379385.

    • Search Google Scholar
    • Export Citation
  • 33

    Seltzer MA, Barbaric Z, Belldegrun A. Comparison of helical computerized tomography, positron emission tomography and monoclonal antibody scans for evaluation of lymph node metastases in patients with prostate specific antigen relapse after treatment for localized prostate cancer. J Urol 1999;162:13221328.

    • Search Google Scholar
    • Export Citation
  • 34

    Hofer C, Laubenbacher C, Block T, Breul J. Fluorine-18-fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy. Eur Urol 1999;36:3135.

    • Search Google Scholar
    • Export Citation
  • 35

    Pound CR, Partin AW, Epstein JI. Prostate-specific antigen after anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer control. Urol Clin North Am 1997;24:395406.

    • Search Google Scholar
    • Export Citation
  • 36

    Leventis AK, Shariat SF, Kattan MW. Prediction of response to salvage radiation therapy in patients with prostate cancer recurrence after radical prostatectomy. J Clin Oncol 2001;19:10301039.

    • Search Google Scholar
    • Export Citation
  • 37

    Sartor CI, Strawderman MH, Lin XH. Rate of PSA rise predicts metastatic versus local recurrence after definitive radiotherapy. Int J Radiat Oncol Biol Phys 1997;38:941947.

    • Search Google Scholar
    • Export Citation
  • 38

    Cox JD, Gallagher MJ, Hammond EH. Consensus statements on radiation therapy of prostate cancer: guidelines for prostate re-biopsy after radiation and for radiation therapy with rising prostate-specific antigen levels after radical prostatectomy. American Society for Therapeutic Radiology and Oncology Consensus Panel. J Clin Oncol 1999;17:1155.

    • Search Google Scholar
    • Export Citation
  • 39

    Cadeddu JA, Partin AW, DeWeese TL, Walsh PC. Long-term results of radiation therapy for prostate cancer recurrence following radical prostatectomy. J Urol 1998;159:173177.

    • Search Google Scholar
    • Export Citation
  • 40

    Morris MM, Dallow KC, Zietman AL. Adjuvant and salvage irradiation following radical prostatectomy for prostate cancer. Int J Radiat Oncol Biol Phys 1997;38:731736.

    • Search Google Scholar
    • Export Citation
  • 41

    Schild SE, Buskirk SJ, Wong WW. The use of radiotherapy for patients with isolated elevation of serum prostate specific antigen following radical prostatectomy. J Urol 1996;156:17251729.

    • Search Google Scholar
    • Export Citation
  • 42

    Wu JJ, King SC, Montana GS. The efficacy of postprostatectomy radiotherapy in patients with an isolated elevation of serum prostate-specific antigen. Int J Radiat Oncol Biol Phys 1995;32:317323.

    • Search Google Scholar
    • Export Citation
  • 43

    Katz MS, Zelefsky MJ, Venkatraman ES. Predictors of biochemical outcome with salvage conformal radiotherapy after radical prostatectomy for prostate cancer. J Clin Oncol 2003;21:483489.

    • Search Google Scholar
    • Export Citation
  • 44

    Catton C, Gospodarowicz M, Warde P. Adjuvant and salvage radiation therapy after radical prostatectomy for adenocarcinoma of the prostate. Radiother Oncol 2001;59:5160.

    • Search Google Scholar
    • Export Citation
  • 45

    Garg MK, Tekyi-Mensah S, Bolton S. Impact of postprostatectomy prostate-specific antigen nadir on outcomes following salvage radiotherapy. Urology 1998;51:9981002.

    • Search Google Scholar
    • Export Citation
  • 46

    Zelefsky MJ, Aschkenasy E, Kelsen S. Tolerance and early outcome results of postprostatectomy three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys 1997;39:327333.

    • Search Google Scholar
    • Export Citation
  • 47

    Crane CH, Rich TA, Read PW. Preirradiation PSA predicts biochemical disease-free survival in patients treated with postprostatectomy external beam irradiation. Int J Radiat Oncol Biol Phys 1997;39:681686.

    • Search Google Scholar
    • Export Citation
  • 48

    Stephenson AJ, Shariat SF, Kattan MW. Predicting the outcome of salvage radiotherapy for suspected local recurrence of prostate cancer after radical prostatectomy (Abstr #1577). Proc Am Soc Clin Oncol 2003;22:392.

    • Search Google Scholar
    • Export Citation
  • 49

    Rogers E, Ohori M, Kassabian VS. Salvage radical prostatectomy: outcome measured by serum prostate specific antigen levels. J Urol 1995;153:104110.

    • Search Google Scholar
    • Export Citation
  • 50

    Gheiler EL, Tefilli MV, Tiguert R. Predictors for maximal outcome in patients undergoing salvage surgery for radio-recurrent prostate cancer. Urology 1998;51:789795.

    • Search Google Scholar
    • Export Citation
  • 51

    Lerner SE, Blute ML, Zincke H. Critical evaluation of salvage surgery for radio-recurrent/resistant prostate cancer. J Urol 1995;154:11031109.

    • Search Google Scholar
    • Export Citation
  • 52

    Brenner PC, Russo P, Wood DP, Morse MJ. Salvage radical prostatectomy in the management of locally recurrent prostate cancer after 125I implantation. Br J Urol 1995;75:4447.

    • Search Google Scholar
    • Export Citation
  • 53

    Losa A, Nava LD, Di Muzio N: Salvage brachytherapy for local recurrence after radical prostatectomy and subsequent external beam radiotherapy. Urology 2003;62:10681072.

    • Search Google Scholar
    • Export Citation
  • 54

    Grado GL, Collins JM, Kriegshauser JS. Salvage brachytherapy for localized prostate cancer after radiotherapy failure. Urology 1999;53:210.

  • 55

    Izawa JI, Madsen LT, Scott SM: Salvage cryotherapy for recurrent prostate cancer after radiotherapy: variables affecting patient outcome. J Clin Oncol 2002;20:26642671.

    • Search Google Scholar
    • Export Citation
  • 56

    Chin JL, Pautler SE, Mouraviev V. Results of salvage cryoablation of the prostate after radiation: identifying predictors of treatment failure and complications. J Urol 2001;165:19371941.

    • Search Google Scholar
    • Export Citation
  • 57

    Tunn UW, Eckart O, Offenbach DE. Can intermittent androgen deprivation be an alternative to continuous androgen withdrawal in patients with PSA relapse? First results of the randomized prospective phase III clinical trial EC 507 (Abstr #1481). J Urol 2003;169.

    • Search Google Scholar
    • Export Citation
  • 58

    Tyrrell CJ, Kaisarry AV, Iversen P. A randomized comparison of bicalutamide 150mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol 1998;33:447456.

    • Search Google Scholar
    • Export Citation
  • 59

    Iversen P, Tyrrell CJ, Kaisary AV. Bicalutamide 150mg monotherapy compared with castration in patients with non-metastatic, locally advanced prostate cancer. J Urol 2000;164:15791582.

    • Search Google Scholar
    • Export Citation
  • 60

    See WA, Wirth MP, McLeod DG. Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program. J Urol 2002;168:429435.

    • Search Google Scholar
    • Export Citation
  • 61

    Eisenberger MA, Blumenstein BA, Crawford ED. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med 1998;339:10361042.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 285 231 11
PDF Downloads 87 72 10
EPUB Downloads 0 0 0