Tipos de Cancer   /   Cáncer de la Próstata

NCI/PDQ^® Health professionals: Prostate Cancer Treatment (PDQ®)

National Cancer Institute
Ultima Vez Modificado: 21 de septiembre del 2012

TABLE OF CONTENTS

• General Information About Prostate Cancer
  • Incidence and Mortality
  • Related Summaries

• Cellular Classification of Prostate Cancer

• Stage Information for Prostate Cancer
  • Definitions of TNM

• Treatment Option Overview
  • Surgical Complications
  • Radiation Therapy Complications
  • Cryotherapy Complications
  • Hormone Therapy Complications

• Stage I Prostate Cancer
  • Current Clinical Trials

• Stage II Prostate Cancer

• Current Clinical Trials

• Stage III Prostate Cancer
  • Current Clinical Trials

• Stage IV Prostate Cancer
  • Current Clinical Trials

• Recurrent Prostate Cancer
  • Overview
  • Chemotherapy for Hormone-Refractory Prostate Cancer
  • Immunotherapy
  • Hormonal Approaches
  • Current Clinical Trials

• Changes to This Summary (09/21/2012)

• About This PDQ® Summary
  • Purpose of This Summary
  • Reviewers and Updates
  • Levels of Evidence
  • Permission to Use This Summary
  • Disclaimer
  • Contact Us

• Get More Information From NCI

General Information About Prostate Cancer

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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 patientsespecially those with localized tumorsmay 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 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], 0.790.91; 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 yearsa 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 (US) is controversial. 7 8 Serum PSA and transrectal US 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 [PUBMED Abstract]
2. Garnick MB: Prostate cancer: screening, diagnosis, and management. Ann Intern Med 118 (10): 804-18, 1993. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
7. Krahn MD, Mahoney JE, Eckman MH, et al.: Screening for prostate cancer. A decision analytic view. JAMA 272 (10): 773-80, 1994. [PUBMED Abstract]
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. [PUBMED Abstract]
9. Hinman F Jr: Screening for prostatic carcinoma. J Urol 145 (1): 126-9; discussion 129-30, 1991. [PUBMED Abstract]
10. Gerber GS, Chodak GW: Routine screening for cancer of the prostate. J Natl Cancer Inst 83 (5): 329-35, 1991. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
15. Gittes RF: Carcinoma of the prostate. N Engl J Med 324 (4): 236-45, 1991. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
42. Andriole GL: Serum prostate-specific antigen: the most useful tumor marker. J Clin Oncol 10 (8): 1205-7, 1992. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
51. Baker SG: Surrogate endpoints: wishful thinking or reality? J Natl Cancer Inst 98 (8): 502-3, 2006. [PUBMED Abstract]
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. [PUBMED Abstract]

Cellular Classification of Prostate Cancer

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More than 95% of primary prostate cancers are adenocarcinomas, and this discussion is confined to patients with this diagnosis. In general, the degree of tumor differentiation and abnormality of histologic growth pattern directly correlate with the likelihood of metastases and with death. Because of marked variability in tumor differentiation from one microscopic field to another, many pathologists will report the range of differentiation among the malignant cells that are present in a biopsy (Gleason grade). 1 2

When the cytopathologist is experienced in the technique, and the specimen is adequate for analysis, fine-needle aspiration of the prostate (usually performed transrectally) has been shown to have an accuracy of diagnosis equal to that of traditional core-needle biopsy. 3 Fine-needle aspiration is less painful than core biopsy and, therefore, can be performed as an outpatient procedure and at periodic intervals for serial follow-up. Controversy exists as to whether it is as reliable for grading purposes, particularly with grade range apparent in different fields. 4 Many urologists now use a bioptic gun with ultrasound (US) guidance, which is relatively painless. The risk of complications with this technique is low. A transperineal, US-guided approach can be used in those patients who may be at increased risk of complications through a transrectal approach. 5 In a series of 670 men undergoing biopsy with an 18-gauge needle, the complication rate was 2% with only 4 patients requiring hospitalization. 6

References:

1. Gleason DF, Mellinger GT: Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 111 (1): 58-64, 1974. [PUBMED Abstract]
2. Gleason DF: Histologic grading and clinical staging of prostatic carcinoma. In: Tannenbaum M: Urologic Pathology: The Prostate. Philadelphia, Pa: Lea and Febiger, 1977, pp 171-197. [PUBMED Abstract]
3. Ljung BM, Cherrie R, Kaufman JJ: Fine needle aspiration biopsy of the prostate gland: a study of 103 cases with histological followup. J Urol 135 (5): 955-8, 1986. [PUBMED Abstract]
4. Algaba F, Epstein JI, Aldape HC, et al.: Assessment of prostate carcinoma in core needle biopsy--definition of minimal criteria for the diagnosis of cancer in biopsy material. Cancer 78 (2): 376-81, 1996. [PUBMED Abstract]
5. Webb JA, Shanmuganathan K, McLean A: Complications of ultrasound-guided transperineal prostate biopsy. A prospective study. Br J Urol 72 (5 Pt 2): 775-7, 1993. [PUBMED Abstract]
6. Desmond PM, Clark J, Thompson IM, et al.: Morbidity with contemporary prostate biopsy. J Urol 150 (5 Pt 1): 1425-6, 1993. [PUBMED Abstract]

Stage Information for Prostate Cancer

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Detection of asymptomatic metastatic disease in prostate cancer is greatly affected by the staging tests performed. Radionuclide bone scans are currently the most widely used tests for metastases to the bone, which is the most common site of distant tumor spread. Magnetic resonance imaging (MRI) is more sensitive than radionuclide bone scans but is impractical for evaluating the entire skeletal system. Some evidence suggests that serum prostate-specific antigen (PSA) levels can predict the results of radionuclide bone scan in newly diagnosed patients. In one series, only 2 of 852 patients (0.23%) with a PSA of less than 20 g/L had a positive bone scan in the absence of bone pain. 1 In another series of 265 prostate cancer patients, 0 of 23 patients with a PSA of less than 4 ¼g/L had a positive bone scan, and 2 of 114 patients with a PSA of less than 10 AMBERSANDCHAR188;g/L had a positive bone scan. 2 Prognosis is worse in patients with pelvic lymph node involvement.

Whether to subject all patients to a pelvic lymph node dissection (PLND) is debatable, but in patients undergoing a radical retropubic prostatectomy, the nodal status is ascertained as a matter of course. In patients who are undergoing a radical perineal prostatectomy in whom the PSA value is less than 20 and the Gleason sum is low, however, evidence is mounting that a PLND is probably unnecessary, especially in patients whose malignancy was not palpable but detected on ultrasound (US). 3 4 A PLND remains the most accurate method to assess metastases to pelvic nodes, and laparoscopic PLND has been shown to accurately assess pelvic nodes as effectively as an open procedure. 5 The exact role of PLND in diagnosis and subsequent treatment is being evaluated, though it has already been determined that the length of hospital stay following laparoscopic PLND is shorter than that following an open procedure. The determining factor when deciding if any type of PLND is indicated is whether definitive therapy may be altered. Likewise, preoperative seminal vesicle biopsy may be useful in patients with palpable nodules who are being considered for radical prostatectomy (unless they have a low Gleason score) because seminal vesicle involvement could affect choice of primary therapy and predicts for pelvic lymph node metastasis. 6

In patients with clinically localized (stage I or stage II) prostate cancer, Gleason pathologic grade and enzymatic serum prostatic acid phosphatase values (even within normal range) predict the likelihood of capsular penetration, seminal vesicle invasion, or regional lymph node involvement. 3 Analysis of a series of 166 patients with clinical stage I and stage II prostate cancer undergoing radical prostatectomy revealed an association between Gleason biopsy score and the risk of lymph node metastasis found at surgery. The risks of node metastasis for patients grouped according to their Gleason biopsy score was 2%, 13%, and 23% for Gleason scores of 5, 6, and 8, respectively. 7

Transrectal US (TRUS) may facilitate diagnosis by directing needle biopsy; however, US is operator dependent and does not assess lymph node size. Moreover, a prospective, multi-institutional study of preoperative TRUS in men with clinically localized prostate cancer felt to be eligible for radical prostatectomy showed that TRUS was no better than digital rectal examination in predicting extracapsular tumor extension or seminal vesicle involvement. 8 Computed tomography (CT) can detect grossly enlarged nodes but poorly defines intraprostatic features; 9 therefore, it is not reliable for the staging of pelvic node disease when compared to surgical staging. 10 Although MRI has been used to detect extracapsular extension of prostate cancer, a positive-predictive value of about 70% and considerable interobserver variation are problems that make its routine use in staging uncertain. 11 US and MRI, however, can reduce clinical understaging and improve patient selection for local therapy. Preliminary data with the endorectal MRI coil for prostate imaging report the highest sensitivity and specificity for identification of organ-confined and extracapsular disease. 3 12 13 MRI is a poor tool for evaluating nodal disease.

Two systems are in common use for the staging of prostate cancer. The Jewett system (stages A through D) was described in 1975 and has since been modified. 14 In 1997, the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer adopted a revised tumor, nodes, metastasis (TNM) system that employs the same broad T stage categories as the Jewett system but includes subcategories of T stage, such as a stage to describe patients diagnosed through PSA screening. This revised TNM system is clinically useful and more precisely stratifies newly diagnosed patients. The AJCC further revised the TNM classification system in 2002 and, most recently, in 2010. 15 Both staging systems are shown below, and both are used in this summary to discuss treatment options. A thorough review of the controversies of staging in prostate cancer has been published. 16

Definitions of TNM

The AJCC has designated staging by TNM classification to define prostate cancer. 15

Table 1. Primary Tumor (T)^a

^aReprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457-68.^bTumor found in one or both lobes by needle biopsy, but not palpable or reliably visible by imaging, is classified as T1c.^cInvasion into the prostatic apex or into (but not beyond) the prostatic capsule is classified not as T3 but as T2.

Clinical
TX	Primary tumor cannot be assessed.
T0	No evidence of primary tumor.
T1	Clinically inapparent tumor neither palpable nor visible by imaging.
T1a	Tumor incidental histologic finding in 5% of tissue resected.
T1b	Tumor incidental histologic finding in >5% of tissue resected.
T1c	Tumor identified by needle biopsy (e.g., because of elevated PSA).
T2	Tumor confined within prostate.b
T2a	Tumor involves one-half of one lobe.
T2b	Tumor involves >one-half of one lobe but not both lobes.
T2c	Tumor involves both lobes.
T3	Tumor extends through the prostate capsule.c
T3a	Extracapsular extension (unilateral or bilateral).
T3b	Tumor invades seminal vesicle(s).
T4	Tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall.

Table 2. Pathologic (pT)^a,b

^aReprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457-68.^bThere is no pathologic T1 classification.^cPositive surgical margin should be indicated by an R1 descriptor (residual microscopic disease).

pT2	Organ confined.
pT2a	Unilateral, one-half of one side.
pT2b	Unilateral, involving >one-half of side but not both sides.
pT2c	Bilateral disease.
pT3	Extraprostatic extension.
pT3a	Extraprostatic extension or microscopic invasion of bladder neck.c
pT3b	Seminal vesicle invasion.
pT4	Invasion of rectum, levator muscles, and/or pelvic wall.

Table 3. Regional Lymph Nodes (N)^a

^aReprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457-68.

Clinical
NX	Regional lymph nodes were not assessed.
N0	No regional lymph node metastasis.
N1	Metastases in regional lymph node(s).
Pathologic
pNX	Regional nodes not sampled.
pN0	No positive regional nodes.
pN1	Metastases in regional node(s).

Table 4. Distant Metastasis (M)^a,b

^aReprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457-68.^bWhen more than one site of metastasis is present, the most advanced category is used. pM1c is most advanced.

M0	No distant metastasis.
M1	Distant metastasis.
M1a	Nonregional lymph node(s).
M1b	Bone(s).
M1c	Other site(s) with or without bone disease.

Table 5. Anatomic Stage/Prognostic Groups^ab

^aReprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457-68.^bWhen either PSA or Gleason is not available, grouping should be determined by T stage and/or either PSA or Gleason as available.

Group	T	N	M	PSA	Gleason
I	T1ac	N0	M0	PSA <10	Gleason 6
	T2a	N0	M0	PSA <10	Gleason 6
	T12a	N0	M0	PSA X	Gleason X
IIA	T1ac	N0	M0	PSA <20	Gleason 7
	T1ac	N0	M0	PSA 10 <20	Gleason 6
	T2a	N0	M0	PSA 10 <20	Gleason 6
	T2a	N0	M0	PSA <20	Gleason 7
	T2b	N0	M0	PSA <20	Gleason 7
	T2b	N0	M0	PSA X	Gleason X
IIB	T2c	N0	M0	Any PSA	Any Gleason
	T12	N0	M0	PSA 20	Any Gleason
	T12	N0	M0	Any PSA	Gleason 8
III	T3ab	N0	M0	Any PSA	Any Gleason
IV	T4	N0	M0	Any PSA	Any Gleason
	Any T	N1	M0	Any PSA	Any Gleason
	Any T	Any N	M1	Any PSA	Any Gleason
PSA = prostate-specific antigen.

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