Font Size
A
A
A
1
...

Prostate Cancer Treatment (Professional)


General Information About Prostate Cancer

Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Incidence and Mortality

Estimated new cases and deaths from prostate cancer in the United States in 2012:[1]

  • New cases: 241,740.
  • Deaths: 28,170.

Carcinoma of the prostate is predominantly a tumor of older men, which frequently responds to treatment when widespread and may be cured when localized. The rate of tumor growth varies from very slow to moderately rapid, and some patients may have prolonged survival even after the cancer has metastasized to distant sites such as bone. Because the median age at diagnosis is 72 years, many patients—especially those with localized tumors—may die of other illnesses without ever having suffered significant disability from the cancer. The approach to treatment is influenced by age and coexisting medical problems. Side effects of various forms of treatment should be considered in selecting appropriate management. Controversy exists in regard to the value of screening, the most appropriate staging evaluation, and the optimal treatment of each stage of the disease.[2]

A complicating feature of any analysis of survival after treatment of prostate cancer and comparison of the various treatment strategies is the evidence of increasing diagnosis of nonlethal tumors as diagnostic methods have changed over time. Nonrandomized comparisons of treatments may therefore be confounded not only by patient-selection factors but also by time trends. For example, a population-based study in Sweden showed that from 1960 to the late 1980s, before the use of prostate-specific antigen (PSA) for screening purposes, long-term relative survival rates after the diagnosis of prostate cancer improved substantially as more sensitive methods of diagnosis were introduced. This occurred despite the use of watchful waiting or palliative hormonal treatment as the most common treatment strategies for localized prostate cancer during the entire era (<150 radical prostatectomies per year were performed in Sweden during the late 1980s). The investigators estimated that if all cancers diagnosed between 1960 and 1964 were of the lethal variety, then at least 33% of cancers diagnosed between 1980 and 1984 were of the nonlethal variety.[3][Level of evidence: 3iB] With the advent of PSA screening, the ability to diagnose nonlethal prostate cancers may increase further. Another issue complicating comparisons of outcomes among nonconcurrent series of patients is the possibility of changes in criteria for histologic diagnosis of prostate cancer.[4] This phenomenon creates a statistical artifact that can produce a false sense of therapeutic accomplishment and may also lead to more aggressive therapy. For example, prostate biopsies from a population-based cohort of 1,858 men diagnosed with prostate cancer from 1990 through 1992 were re-read in 2002 to 2004.[5,6] The contemporary Gleason score readings were an average of 0.85 points higher (95% confidence interval [CI], 0.79–0.91; P < .001) than the same slides read in 1990 to 1992. As a result, Gleason score-standardized prostate cancer mortality for these men was artifactually improved from 2.08 to 1.50 deaths per 100 person years—a 28% decrease even though overall outcomes were unchanged.

The issue of screening asymptomatic men for prostate cancer with digital rectal examination (DRE), PSA, and/or ultrasound is controversial.[7,8] Serum PSA and transrectal ultrasound are more sensitive and will increase the diagnostic yield of prostate cancer when used in combination with rectal examination; however, these screening methods are also associated with high false-positive rates and may identify some tumors that will not threaten the patient's health.[9,10,11,12] The issue is further complicated by the morbidity associated with work-up and treatment of such tumors and the considerable cost beyond a routine DRE. Furthermore, because a high percentage of tumors identified by PSA screening alone have spread outside the prostate, PSA screening may not improve life expectancy. In any case, the clinician who uses PSA for the detection of prostate cancer should be aware that no uniform standard exists; if a laboratory changes to a different assay kit, serial assays may yield nonequivalent PSA values.[13] In addition, the upper limit of the normal range of PSA, and therefore the threshold at which to biopsy, is not well defined.[14] A multicenter trial (PLCO-1) that was sponsored by the National Cancer Institute was conducted to test the value of early detection in reducing mortality. (Refer to the PDQ summary on Prostate Cancer Screening for more information.)

Survival of the patient with prostatic carcinoma is related to the extent of the tumor. When the cancer is confined to the prostate gland, median survival in excess of 5 years can be anticipated. Patients with locally advanced cancer are not usually curable, and a substantial fraction will eventually die of the tumor, though median survival may be as long as 5 years. If prostate cancer has spread to distant organs, current therapy will not cure it. Median survival is usually 1 to 3 years, and most such patients will die of prostate cancer. Even in this group of patients, however, indolent clinical courses lasting for many years may be observed.

Other factors affecting the prognosis of patients with prostate cancer that may be useful in making therapeutic decisions include histologic grade of the tumor, patient's age, other medical illnesses, and level of PSA.[15,16,17,18,19] Poorly differentiated tumors are more likely to have already metastasized by the time of diagnosis and are associated with a poorer prognosis. For patients treated with radiation therapy, the combination of clinical tumor stage, Gleason score, and pretreatment PSA level can be used to more accurately estimate the risk of relapse.[20][Level of evidence: 3iDii] In most studies, flow cytometry has shown that nuclear DNA ploidy is an independent prognostic indicator for progression and for cause-specific survival in patients with pathologic stages III and IV prostate cancer without metastases (Jewett stages C and D1). Diploid tumors have a more favorable outcome than either tetraploid or aneuploid tumors. The use of flow cytometry techniques and histogram analysis to determine prognosis will require standardization.[21,22,23,24]

Often, baseline rates of PSA changes are thought to be markers of tumor progression. Even though a tumor marker or characteristic may be consistently associated with a high risk of prostate cancer progression or death, it may be a very poor predictor and therefore of very limited utility in making therapeutic decisions. For example, baseline PSA and rate of PSA change were associated with subsequent metastasis or prostate cancer death in a cohort of 267 men with clinically localized prostate cancer who were managed by watchful waiting in the control arm of a randomized trial comparing radical prostatectomy to watchful waiting.[25,26] Nevertheless, the accuracy of classifying men into groups whose cancer remained indolent versus those whose cancer progressed was poor at all examined cut points of PSA or PSA rate of change.

Several nomograms have been developed to predict outcomes either prior to [27,28,29,30] or after [31,32] radical prostatectomy with intent to cure. Preoperative nomograms are based on clinical stage, PSA, Gleason score, and the number of positive and negative prostate biopsy cores. One independently validated nomogram demonstrated increased accuracy in predicting biochemical recurrence-free survival by including preoperative plasma levels of transforming growth factor B1 and interleukin-6 soluble receptor.[33,34] Postoperative nomograms add pathologic findings, such as capsular invasion, surgical margins, seminal vesicle invasion, and lymph node involvement. The nomograms, however, were developed at academic centers and may not be as accurate when generalized to nonacademic hospitals, where the majority of patients are treated.[35,36] In addition, the nomograms use nonhealth (intermediate) outcomes such as PSA rise or pathologic surgical findings and subjective endpoints such as the physician's perceived need for additional therapy. In addition, the nomograms may be affected by changing methods of diagnosis or neoadjuvant therapy.[28]

Definitive treatment is usually considered for younger men with prostate cancer and no major comorbid medical illnesses because younger men are more likely to die of prostate cancer than older men or men with major comorbid medical illness. Elevations of serum acid phosphatase are associated with poor prognosis in both localized and disseminated disease. PSA, an organ-specific marker with greater sensitivity and high specificity for prostate tissue, is often used as a tumor marker.[17,18,37,38,39,40,41,42] After radical prostatectomy, detectable PSA levels identify patients at elevated risk of local treatment failure or metastatic disease;[39] however, a substantial proportion of patients with elevated or rising PSA levels after surgery may remain clinically free of symptoms for extended periods of time.[43] Biochemical evidence of failure on the basis of elevated or slowly rising PSA alone therefore may not be sufficient to alter treatment. For example, in a retrospective analysis of nearly 2,000 men who had undergone radical prostatectomy with curative intent and who were followed for a mean of 5.3 years, 315 men (15%) demonstrated an abnormal PSA of 0.2 ng/mL or higher, which is evidence of biochemical recurrence. Of these 315 men, 103 men (34%) developed clinical evidence of recurrence. The median time to development of clinical metastasis after biochemical recurrence was 8 years. After the men developed metastatic disease, the median time to death was an additional 5 years.[44]

After radiation therapy with curative intent, persistently elevated or rising PSA may be a prognostic factor for clinical disease recurrence; however, reported case series have used a variety of definitions of PSA failure. Criteria have been developed by the American Society for Therapeutic Radiology and Oncology Consensus Panel.[45,46] It is difficult to base decisions about instituting additional therapy on biochemical failure. The implication of the various definitions of PSA failure for overall survival (OS) is not known, and as in the surgical series, many biochemical relapses (rising PSA alone) may not be clinically manifested in patients treated with radiation therapy.[47,48]

Using surrogate endpoints for clinical decision making is controversial. Preliminary data from a retrospective cohort of 8,669 patients with clinically localized prostate cancer treated with either radical prostatectomy or radiation therapy suggested that short posttreatment PSA doubling time (<3 months in this study) fulfills some criteria as a surrogate endpoint for all-cause mortality and prostate cancer mortality after surgery or radiation therapy.[49] Likewise, a retrospective analysis has shown that PSA declines of 20% to 40% (but not 50%) at 3 months and 30% or more at 2 months after initiation of chemotherapy for hormone-independent prostate cancer, fulfilled several criteria of surrogacy for OS.[50] These observations should be independently confirmed in prospective study designs and may not apply to patients treated with hormonal therapy. In addition, there are no standardized criteria of surrogacy or standardized cutpoints for adequacy of surrogate endpoints, even in prospective trials.[51]

After hormonal therapy, reduction of PSA to undetectable levels provides information regarding the duration of progression-free status;[17] however, decreases in PSA of less than 80% may not be very predictive.[17] Yet, because PSA expression itself is under hormonal control, androgen-deprivation therapy can decrease the serum level of PSA independent of tumor response. Clinicians, therefore, cannot rely solely on the serum PSA level to monitor a patient's response to hormone therapy; they must also follow clinical criteria.[52]

Related Summaries

Other PDQ summaries containing information related to prostate cancer include the following:

  • Genetics of Prostate Cancer
  • Prostate Cancer Prevention
  • Prostate Cancer Screening

References:

  1. American Cancer Society.: Cancer Facts and Figures 2012. Atlanta, Ga: American Cancer Society, 2012. Available online. Last accessed January 5, 2012.
  2. Garnick MB: Prostate cancer: screening, diagnosis, and management. Ann Intern Med 118 (10): 804-18, 1993.
  3. Helgesen F, Holmberg L, Johansson JE, et al.: Trends in prostate cancer survival in Sweden, 1960 through 1988: evidence of increasing diagnosis of nonlethal tumors. J Natl Cancer Inst 88 (17): 1216-21, 1996.
  4. Berner A, Harvei S, Skjorten FJ: Follow-up of localized prostate cancer, with emphasis on previous undiagnosed incidental cancer. BJU Int 83 (1): 47-52, 1999.
  5. Albertsen PC, Hanley JA, Barrows GH, et al.: Prostate cancer and the Will Rogers phenomenon. J Natl Cancer Inst 97 (17): 1248-53, 2005.
  6. Thompson IM, Canby-Hagino E, Lucia MS: Stage migration and grade inflation in prostate cancer: Will Rogers meets Garrison Keillor. J Natl Cancer Inst 97 (17): 1236-7, 2005.
  7. Krahn MD, Mahoney JE, Eckman MH, et al.: Screening for prostate cancer. A decision analytic view. JAMA 272 (10): 773-80, 1994.
  8. Kramer BS, Brown ML, Prorok PC, et al.: Prostate cancer screening: what we know and what we need to know. Ann Intern Med 119 (9): 914-23, 1993.
  9. Hinman F Jr: Screening for prostatic carcinoma. J Urol 145 (1): 126-9; discussion 129-30, 1991.
  10. Gerber GS, Chodak GW: Routine screening for cancer of the prostate. J Natl Cancer Inst 83 (5): 329-35, 1991.
  11. Catalona WJ, Smith DS, Ratliff TL, et al.: Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 324 (17): 1156-61, 1991.
  12. Welch HG, Albertsen PC: Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986-2005. J Natl Cancer Inst 101 (19): 1325-9, 2009.
  13. Takayama TK, Vessella RL, Lange PH: Newer applications of serum prostate-specific antigen in the management of prostate cancer. Semin Oncol 21 (5): 542-53, 1994.
  14. 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 350 (22): 2239-46, 2004.
  15. Gittes RF: Carcinoma of the prostate. N Engl J Med 324 (4): 236-45, 1991.
  16. Paulson DF, Moul JW, Walther PJ: Radical prostatectomy for clinical stage T1-2N0M0 prostatic adenocarcinoma: long-term results. J Urol 144 (5): 1180-4, 1990.
  17. Matzkin H, Eber P, Todd B, et al.: Prognostic significance of changes in prostate-specific markers after endocrine treatment of stage D2 prostatic cancer. Cancer 70 (9): 2302-9, 1992.
  18. Pisansky TM, Cha SS, Earle JD, et al.: Prostate-specific antigen as a pretherapy prognostic factor in patients treated with radiation therapy for clinically localized prostate cancer. J Clin Oncol 11 (11): 2158-66, 1993.
  19. Chodak GW, Thisted RA, Gerber GS, et al.: Results of conservative management of clinically localized prostate cancer. N Engl J Med 330 (4): 242-8, 1994.
  20. Pisansky TM, Kahn MJ, Rasp GM, et al.: A multiple prognostic index predictive of disease outcome after irradiation for clinically localized prostate carcinoma. Cancer 79 (2): 337-44, 1997.
  21. Nativ O, Winkler HZ, Raz Y, et al.: Stage C prostatic adenocarcinoma: flow cytometric nuclear DNA ploidy analysis. Mayo Clin Proc 64 (8): 911-9, 1989.
  22. Lee SE, Currin SM, Paulson DF, et al.: Flow cytometric determination of ploidy in prostatic adenocarcinoma: a comparison with seminal vesicle involvement and histopathological grading as a predictor of clinical recurrence. J Urol 140 (4): 769-74, 1988.
  23. Ritchie AW, Dorey F, Layfield LJ, et al.: Relationship of DNA content to conventional prognostic factors in clinically localised carcinoma of the prostate. Br J Urol 62 (3): 245-60, 1988.
  24. Lieber MM: Pathological stage C (pT3) prostate cancer treated by radical prostatectomy: clinical implications of DNA ploidy analysis. Semin Urol 8 (4): 219-24, 1990.
  25. Fall K, Garmo H, Andrén O, et al.: Prostate-specific antigen levels as a predictor of lethal prostate cancer. J Natl Cancer Inst 99 (7): 526-32, 2007.
  26. Parekh DJ, Ankerst DP, Thompson IM: Prostate-specific antigen levels, prostate-specific antigen kinetics, and prostate cancer prognosis: a tocsin calling for prospective studies. J Natl Cancer Inst 99 (7): 496-7, 2007.
  27. Partin AW, Kattan MW, Subong EN, et al.: Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. JAMA 277 (18): 1445-51, 1997.
  28. Partin AW, Mangold LA, Lamm DM, et al.: Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology 58 (6): 843-8, 2001.
  29. Kattan MW, Eastham JA, Stapleton AM, et al.: A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst 90 (10): 766-71, 1998.
  30. Stephenson AJ, Scardino PT, Eastham JA, et al.: Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Natl Cancer Inst 98 (10): 715-7, 2006.
  31. Kattan MW, Wheeler TM, Scardino PT: Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. J Clin Oncol 17 (5): 1499-507, 1999.
  32. Stephenson AJ, Scardino PT, Eastham JA, et al.: Postoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Clin Oncol 23 (28): 7005-12, 2005.
  33. Shariat SF, Walz J, Roehrborn CG, et al.: External validation of a biomarker-based preoperative nomogram predicts biochemical recurrence after radical prostatectomy. J Clin Oncol 26 (9): 1526-31, 2008.
  34. Kattan MW, Shariat SF, Andrews B, et al.: The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer. J Clin Oncol 21 (19): 3573-9, 2003.
  35. Penson DF, Grossfeld GD, Li YP, et al.: How well does the Partin nomogram predict pathological stage after radical prostatectomy in a community based population? Results of the cancer of the prostate strategic urological research endeavor. J Urol 167 (4): 1653-7; discussion 1657-8, 2002.
  36. Greene KL, Meng MV, Elkin EP, et al.: Validation of the Kattan preoperative nomogram for prostate cancer recurrence using a community based cohort: results from cancer of the prostate strategic urological research endeavor (capsure). J Urol 171 (6 Pt 1): 2255-9, 2004.
  37. Carlton JC, Zagars GK, Oswald MJ: The role of serum prostatic acid phosphatase in the management of adenocarcinoma of the prostate with radiotherapy. Int J Radiat Oncol Biol Phys 19 (6): 1383-8, 1990.
  38. Stamey TA, Yang N, Hay AR, et al.: Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 317 (15): 909-16, 1987.
  39. Stamey TA, Kabalin JN: Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. I. Untreated patients. J Urol 141 (5): 1070-5, 1989.
  40. Stamey TA, Kabalin JN, McNeal JE, et al.: Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. II. Radical prostatectomy treated patients. J Urol 141 (5): 1076-83, 1989.
  41. Stamey TA, Kabalin JN, Ferrari M: Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. III. Radiation treated patients. J Urol 141 (5): 1084-7, 1989.
  42. Andriole GL: Serum prostate-specific antigen: the most useful tumor marker. J Clin Oncol 10 (8): 1205-7, 1992.
  43. Frazier HA, Robertson JE, Humphrey PA, et al.: Is prostate specific antigen of clinical importance in evaluating outcome after radical prostatectomy. J Urol 149 (3): 516-8, 1993.
  44. Pound CR, Partin AW, Eisenberger MA, et al.: Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281 (17): 1591-7, 1999.
  45. Consensus statement: guidelines for PSA following radiation therapy. American Society for Therapeutic Radiology and Oncology Consensus Panel. Int J Radiat Oncol Biol Phys 37 (5): 1035-41, 1997.
  46. Roach M 3rd, Hanks G, Thames H Jr, et al.: Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 65 (4): 965-74, 2006.
  47. Kuban DA, el-Mahdi AM, Schellhammer PF: Prostate-specific antigen for pretreatment prediction and posttreatment evaluation of outcome after definitive irradiation for prostate cancer. Int J Radiat Oncol Biol Phys 32 (2): 307-16, 1995.
  48. Sandler HM, Dunn RL, McLaughlin PW, et al.: Overall survival after prostate-specific-antigen-detected recurrence following conformal radiation therapy. Int J Radiat Oncol Biol Phys 48 (3): 629-33, 2000.
  49. D'Amico AV, Moul JW, Carroll PR, et al.: Surrogate end point for prostate cancer-specific mortality after radical prostatectomy or radiation therapy. J Natl Cancer Inst 95 (18): 1376-83, 2003.
  50. Petrylak DP, Ankerst DP, Jiang CS, et al.: Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99-16. J Natl Cancer Inst 98 (8): 516-21, 2006.
  51. Baker SG: Surrogate endpoints: wishful thinking or reality? J Natl Cancer Inst 98 (8): 502-3, 2006.
  52. Ruckle HC, Klee GG, Oesterling JE: Prostate-specific antigen: concepts for staging prostate cancer and monitoring response to therapy. Mayo Clin Proc 69 (1): 69-79, 1994.
1
...
eMedicineHealth Public Information from the National Cancer Institute

This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER

This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.

Some material in CancerNet™ is from copyrighted publications of the respective copyright claimants. Users of CancerNet™ are referred to the publication data appearing in the bibliographic citations, as well as to the copyright notices appearing in the original publication, all of which are hereby incorporated by reference.






Medical Dictionary