Current Clinical Trials

Note: 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.)

Stage I prostate cancer is defined by the following staging systems:

• American Joint Committee on Cancer's (AJCC) TNM classification system: T1a, N0, M0, G1 (Gleason score of 2–4).
• Jewett staging system: stage A1.

 [Note: Previous versions of the AJCC staging system described a tumor’s grade as well-differentiated, but this term is no longer used. G1 is the equivalent of well-differentiated.]

The frequency of clinically silent, nonmetastatic prostate cancer that can be found at autopsy greatly increases with age and may be as high as 50% to 60% in men aged 90 years and older. Undoubtedly, the incidental discovery of these occult cancers at prostatic surgery performed for other reasons accounts for the similar survival of men with stage I prostate cancer, compared with the normal male population, adjusted for age. Many stage I cancers are well-differentiated and only focally involve the gland (T1a, N0, M0); most require no treatment other than careful follow-up.[1]

In a retrospective pooled analysis, 828 men with clinically localized prostate cancer were managed by initial conservative therapy with subsequent hormone therapy given at the time of symptomatic disease progression. This study showed that the patients with grade 1 or grade 2 tumors experienced a disease-specific survival of 87% at 10 years and that their overall survival (OS) closely approximated the expected survival among men of similar ages in the general population.[2]

In younger patients (aged 50–60 years) whose expected survival is long, treatment should be considered.[3] Radical prostatectomy, external-beam radiation therapy (EBRT), and interstitial implantation of radioisotopes and watchful waiting yield apparently similar survival rates in noncontrolled selected series. The decision to treat should be made in the context of the patient’s age, associated medical illnesses, and personal desires.[3]

Bicalutamide has not been shown to improve OS in patients with localized or locally advanced prostate cancer. The Early Prostate Cancer program is a large, randomized, placebo-controlled, international trial that compared bicalutamide (150 mg orally per day) plus standard care (radical prostatectomy, radiation therapy, or watchful waiting, depending on local custom) with standard care alone for men with nonmetastatic localized or locally advanced prostate cancer (T1–2, N0, NX; T3–4, any N; or any T, N+).[4] Less than 2% of the 8,113 men had known node disease. At a median follow-up of 7.4 years, there was no difference in OS between the bicalutamide and placebo groups (about 76% in both arms [hazard ratio = 0.99; 95% confidence interval, 0.91–1.09; P = .89]).[4][Level of evidence: 1iA]

Standard treatment options:

1. Careful observation without further immediate treatment in selected patients[2,3,5,6]



2. Radical prostatectomy, usually with pelvic lymphadenectomy (with or without the nerve-sparing technique designed to preserve potency).[7-9] Radical prostatectomy may be difficult after a transurethral resection of the prostate (TURP). Consideration may be given to postoperative radiation therapy for patients who are found to have capsular penetration or seminal vesicle invasion by tumor at the time of prostatectomy or who have a detectable level of prostate-specific antigen (PSA) more than 3 weeks after surgery.[10-15] Because duration of follow-up in available studies is still relatively short, the value of postoperative radiation therapy is yet to be determined; however, postoperative radiation therapy does reduce local recurrence.[16] Careful treatment planning is necessary to avoid morbidity.[10-15] Clinical trials are in progress.



3. EBRT.[17-21] Definitive radiation therapy should be delayed 4 to 6 weeks after TURP to reduce incidence of stricture.[22]



4. Interstitial implantation of radioisotopes (i.e., iodine I 125, palladium, and iridium) done through a transperineal technique with either ultrasound or computed tomography (CT) guidance is being done in carefully selected patients with T1 or T2a tumors. Short-term results in these patients are similar to those for radical prostatectomy or EBRT.[23-25][Level of evidence: 3iiiDiv] One advantage is that the implant is performed as outpatient surgery. The rate of maintenance of sexual potency with interstitial implants has been reported to be 86% to 92%,[23,25] which compares with rates of 10% to 40% with radical prostatectomy and 40% to 60% with EBRT; however, urinary tract frequency, urgency, and less commonly, urinary retention are seen in most patients but subside with time. Rectal ulceration may also be seen. In one series, a 10% 2-year actuarial genitourinary grade 2 complication rate and a 12% risk of rectal ulceration were seen. This risk decreased with increased operator experience and modification of implant technique.[23] Long-term follow-up of these patients is necessary to assess treatment efficacy and side effects.

   Retropubic freehand implantation with iodine I 125 has been associated with an increased local failure and complication rate [26,27] and is now rarely done.

Treatment options under clinical evaluation:

1. High-intensity focused ultrasound.[28]
2. Other clinical trials.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I prostate cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Consensus conference. The management of clinically localized prostate cancer. JAMA 258 (19): 2727-30, 1987.  [PUBMED Abstract]
   
   
2. 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]
   
   
3. Epstein JI, Paull G, Eggleston JC, et al.: Prognosis of untreated stage A1 prostatic carcinoma: a study of 94 cases with extended followup. J Urol 136 (4): 837-9, 1986.  [PUBMED Abstract]
   
   
4. McLeod DG, Iversen P, See WA, et al.: Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer. BJU Int 97 (2): 247-54, 2006.  [PUBMED Abstract]
   
   
5. Graversen PH, Nielsen KT, Gasser TC, et al.: Radical prostatectomy versus expectant primary treatment in stages I and II prostatic cancer. A fifteen-year follow-up. Urology 36 (6): 493-8, 1990.  [PUBMED Abstract]
   
   
6. Cantrell BB, DeKlerk DP, Eggleston JC, et al.: Pathological factors that influence prognosis in stage A prostatic cancer: the influence of extent versus grade. J Urol 125 (4): 516-20, 1981.  [PUBMED Abstract]
   
   
7. Zincke H, Bergstralh EJ, Blute ML, et al.: Radical prostatectomy for clinically localized prostate cancer: long-term results of 1,143 patients from a single institution. J Clin Oncol 12 (11): 2254-63, 1994.  [PUBMED Abstract]
   
   
8. Catalona WJ, Bigg SW: Nerve-sparing radical prostatectomy: evaluation of results after 250 patients. J Urol 143 (3): 538-43; discussion 544, 1990.  [PUBMED Abstract]
   
   
9. Catalona WJ, Basler JW: Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy. J Urol 150 (3): 905-7, 1993.  [PUBMED Abstract]
   
   
10. Lange PH, Reddy PK, Medini E, et al.: Radiation therapy as adjuvant treatment after radical prostatectomy. NCI Monogr (7): 141-9, 1988.  [PUBMED Abstract]
    
    
11. Ray GR, Bagshaw MA, Freiha F: External beam radiation salvage for residual or recurrent local tumor following radical prostatectomy. J Urol 132 (5): 926-30, 1984.  [PUBMED Abstract]
    
    
12. Carter GE, Lieskovsky G, Skinner DG, et al.: Results of local and/or systemic adjuvant therapy in the management of pathological stage C or D1 prostate cancer following radical prostatectomy. J Urol 142 (5): 1266-70; discussion 1270-1, 1989.  [PUBMED Abstract]
    
    
13. Freeman JA, Lieskovsky G, Cook DW, et al.: Radical retropubic prostatectomy and postoperative adjuvant radiation for pathological stage C (PcN0) prostate cancer from 1976 to 1989: intermediate findings. J Urol 149 (5): 1029-34, 1993.  [PUBMED Abstract]
    
    
14. 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]
    
    
15. Hudson MA, Bahnson RR, Catalona WJ: Clinical use of prostate specific antigen in patients with prostate cancer. J Urol 142 (4): 1011-7, 1989.  [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. Bagshaw MA: External radiation therapy of carcinoma of the prostate. Cancer 45 (7 Suppl): 1912-21, 1980.  [PUBMED Abstract]
    
    
18. Forman JD, Zinreich E, Lee DJ, et al.: Improving the therapeutic ratio of external beam irradiation for carcinoma of the prostate. Int J Radiat Oncol Biol Phys 11 (12): 2073-80, 1985.  [PUBMED Abstract]
    
    
19. Ploysongsang S, Aron BS, Shehata WM, et al.: Comparison of whole pelvis versus small-field radiation therapy for carcinoma of prostate. Urology 27 (1): 10-6, 1986.  [PUBMED Abstract]
    
    
20. Pilepich MV, Bagshaw MA, Asbell SO, et al.: Definitive radiotherapy in resectable (stage A2 and B) carcinoma of the prostate--results of a nationwide overview. Int J Radiat Oncol Biol Phys 13 (5): 659-63, 1987.  [PUBMED Abstract]
    
    
21. Amdur RJ, Parsons JT, Fitzgerald LT, et al.: The effect of overall treatment time on local control in patients with adenocarcinoma of the prostate treated with radiation therapy. Int J Radiat Oncol Biol Phys 19 (6): 1377-82, 1990.  [PUBMED Abstract]
    
    
22. Seymore CH, el-Mahdi AM, Schellhammer PF: The effect of prior transurethral resection of the prostate on post radiation urethral strictures and bladder neck contractures. Int J Radiat Oncol Biol Phys 12 (9): 1597-600, 1986.  [PUBMED Abstract]
    
    
23. Wallner K, Roy J, Harrison L: Tumor control and morbidity following transperineal iodine 125 implantation for stage T1/T2 prostatic carcinoma. J Clin Oncol 14 (2): 449-53, 1996.  [PUBMED Abstract]
    
    
24. D'Amico AV, Coleman CN: Role of interstitial radiotherapy in the management of clinically organ-confined prostate cancer: the jury is still out. J Clin Oncol 14 (1): 304-15, 1996.  [PUBMED Abstract]
    
    
25. Ragde H, Blasko JC, Grimm PD, et al.: Interstitial iodine-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma. Cancer 80 (3): 442-53, 1997.  [PUBMED Abstract]
    
    
26. Kuban DA, el-Mahdi AM, Schellhammer PF: I-125 interstitial implantation for prostate cancer. What have we learned 10 years later? Cancer 63 (12): 2415-20, 1989.  [PUBMED Abstract]
    
    
27. Fuks Z, Leibel SA, Wallner KE, et al.: The effect of local control on metastatic dissemination in carcinoma of the prostate: long-term results in patients treated with 125I implantation. Int J Radiat Oncol Biol Phys 21 (3): 537-47, 1991.  [PUBMED Abstract]
    
    
28. Thüroff S, Chaussy C, Vallancien G, et al.: High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol 17 (8): 673-7, 2003.  [PUBMED Abstract]
    
    

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