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 levels of evidence summary for more information.

T1a, N0, M0, moderately differentiated, poorly differentiated, or undifferentiated or T1b, N0, M0 or T1c, N0, M0 or T1, N0, M0 or T2, N0, M0

Treatment options:

For T1b, N0, M0 or T1c, N0, M0 patients:

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

2. External-beam radiation therapy.[3-7] Prophylactic irradiation of clinically or pathologically uninvolved pelvic lymph nodes does not appear to improve overall survival or prostate cancer-specific survival.[8][Level of evidence: 1iiA] Definitive radiation therapy should be delayed 4 to 6 weeks after transurethral resection to reduce incidence of stricture.[9]

3. Radical prostatectomy usually with pelvic lymphadenectomy (with or without the nerve sparing technique designed to preserve potency).[10-12] Radical prostatectomy may be difficult after a transurethral resection of the prostate. 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 have a detectable level of prostate-specific antigen more than 3 weeks after surgery.[13-18] 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.[19] Careful treatment planning is necessary to avoid morbidity.[13-18] Clinical trials are in progress.

4. Interstitial implantation of radioisotopes (i.e., I-125, palladium, iridium) done through a transperineal technique with either ultrasound or 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 external-beam radiation therapy.[20-22][Level of evidence: 3iiiDiii] 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%, [20,22] which compares with rates of 10% to 40% with radical prostatectomy and 40% to 60% with external-beam radiation therapy. 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 1 series, a 10% 2-year actuarial genitourinary grade 2 complication rate and a 12% risk of rectal ulceration was seen. This risk decreased with increased operator experience and modification of implant technique.[20] Long-term follow-up of these patients is necessary to assess treatment efficacy and side effects.

Retropubic freehand implantation with I-125 has been associated with an increased local failure and complication rate [23,24] and is now rarely done.

5. External-beam radiation therapy designed to decrease exposure of normal tissues using methods such as computed tomography-based 3-D conformal treatment planning is under clinical evaluation.[25]

6. Other clinical trials. Refer to PDQ or to CancerNet (http://cancernet.nci.nih.gov) for information on clinical trials for patients with early stage prostate cancer.

Radical prostatectomy, external-beam irradiation, and interstitial implantation of radioisotopes are each employed in the treatment of stage II prostate cancer with apparently similar therapeutic effects. Radical prostatectomy and radiation therapy yield apparently similar survival rates with up to 10 years follow-up. For well-selected patients, radical prostatectomy can achieve 15-year survival comparable to an age-matched population without prostate cancer.[1] Unfortunately, randomized comparative trials of these treatment methods with prolonged follow-up are lacking. Patients with a small palpable cancer (T2a, N0, M0) fare better than patients in whom the disease involves both lobes of the gland (T2b, N0, M0). Patients proven free of node metastases by pelvic lymphadenectomy fare better than patients in whom this staging procedure is not performed; however, this is due to selection of patients who have a more favorable prognosis. Side effects of the various forms of therapy including impotence, incontinence, and bowel injury should be considered in determining which type of treatment to employ. The only randomized study performed to date comparing radical prostatectomy at diagnosis to expectant therapy (careful observation with therapy as needed) in stages I and II cancers did not show a significant difference in survival.[2] However, the trial of 95 patients was not large enough to exclude a small but medically significant difference in overall survival, nor did it include information to measure time to progression, cancer-specific survival, or quality of life. 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 2 tumors experienced a disease-specific survival of 87% at 10 years and that their overall survival closely approximated the expected survival among men of similar ages in the general population.[1] The decision to treat should be made in the context of the patient's age, associated medical illnesses, and the patient's personal desires.

The role of adjuvant hormonal therapy in patients with locally advanced disease has been analyzed by the Agency for Health Care Policy and Research. A majority of patients have more advanced disease, but patients with bulky T2b tumors were included in the study groups re-evaluating the role of adjuvant hormonal therapy in patients with locally advanced disease. Randomized clinical trial evidence comparing radiation therapy to radiation with prolonged androgen suppression has been published. The meta-analysis found a difference in 5-year overall survival in favor of radiation therapy plus continued androgen suppression compared to radiation therapy alone (hazard ratio=0.631, 95% confidence interval=0.479-0.831).[26][Level of evidence: 1iiA]

Treatment options:

1. Radical prostatectomy usually with pelvic lymphadenectomy.[10,11,27,28] If allowed by the extent of tumor, anatomical dissection that preserves nerves necessary for erection avoids impotence postoperatively in some patients.[12,27] 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 a detectable level of prostate-specific antigen more than 3 weeks after surgery. The value of postoperative radiation therapy is yet to be determined. Postoperative radiation therapy does reduce local recurrence; however, it has not been proven to extend survival.[19] Clinical trials are in progress to test these questions. Careful treatment planning is necessary to avoid morbidity.[13-18] The role of preoperative ("neoadjuvant") hormonal therapy is not established at the present time.[29,30] Also, the morphologic changes induced by neoadjuvant androgen ablation may complicate assessment of surgical margins and capsular involvement.[31]

2. External-beam irradiation.[3-7,32] Prophylactic irradiation of clinically or pathologically uninvolved pelvic lymph nodes does not appear to improve overall survival or prostate cancer-specific survival.[8][Level of evidence: 1iiA] Definitive radiation therapy should be delayed 4 to 6 weeks after transurethral resection to reduce incidence of stricture.[9] For patients with bulky T2b tumors, adjuvant hormonal therapy should be considered.[26]

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

4. Interstitial implantation of radioisotopes (i.e., I-125, palladium, iridium) done through a transperineal technique with either ultrasound or CT guidance is being done in carefully selected patients with T1 or T2A tumors. Short term results in these carefully selected patients are similar to those for radical prostatectomy or external-beam radiation therapy.[20-22][Level of evidence: 3iiiDiii] 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%,[20,33] which compares with rates of 10% to 40% with radical prostatectomy and 40% to 60% with external beam-radiation therapy. However, urinary tract frequency, urgency, or less commonly, urinary retention are seen in most patients but subside with time. Rectal ulceration may also be seen. In 1 series, a 10% 2-year actuarial genitourinary grade 2 complication rate and a 12% risk of rectal ulceration was seen. This risk decreased with increased operator experience and modification of implant technique.[20] Long-term follow-up of these patients is necessary to assess treatment efficacy and side effects.

Retropubic freehand implantation with I-125 has been associated with an increased local failure and complication rate [23,24] and is now rarely done.

5. External-beam radiation therapy designed to decrease exposure of normal tissues using methods such as computed tomography-based 3-D conformal treatment planning is under clinical evaluation.[25]

6. Ultrasound-guided percutaneous cryosurgery is under clinical evaluation.

Cryosurgery is a surgical technique that involves destruction of prostate cancer cells by intermittent freezing of the prostate tissue with cryoprobes followed by thawing.[34][Level of evidence: 3iiiDiii] It is less well established than standard prostatectomy and long-term outcomes are not known. Serious toxic effects include bladder outlet injury, urinary incontinence, sexual impotence, and rectal injury. The technique of cryosurgery is under development.

7. Other clinical trials, including trials of neoadjuvant hormonal therapy followed by radical prostatectomy.[35,36]

1. Chodak GW, Thisted RA, Gerber GS, et al.: Results of conservative management of clinically localized prostate cancer. New England Journal of Medicine 330(4): 242-248, 1994.
2. 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): 493-498, 1990.
3. Bagshaw MA: External radiation therapy of carcinoma of prostate. Cancer 45(7): 1912-1921, 1980.
4. Forman JD, Zinreich E, Lee DJ, et al.: Improving the therapeutic ratio of external beam irradiation for carcinoma of the prostate. International Journal of Radiation Oncology, Biology, Physics 11(12): 2073-2080, 1985.
5. Ploysongsang S, Aron BS, Shehata WM, et al.: Comparison of whole pelvis versus small-field radiation therapy for carcinoma of prostate. Urology 27(1): 10-16, 1986.
6. 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. International Journal of Radiation Oncology, Biology, Physics 13(5): 659-663, 1987.
7. 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. International Journal of Radiation Oncology, Biology, Physics 19(6): 1377-1382, 1990.
8. Asbell SO, Martz KL, Shin KH, et al.: Impact of surgical staging in evaluating the radiotherapeutic outcome in RTOG #77-06, a phase III study for T1BN0M0 (A2) and T2N0M0 (B) prostate carcinoma. International Journal of Radiation Oncology, Biology, Physics 40(4): 769-782, 1998.
9. 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. International Journal of Radiation Oncology, Biology, Physics 12(9): 1597-1600, 1986.
10. 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. Journal of Clinical Oncology 12(11): 2254-2263, 1994.
11. Catalona WJ, Bigg SW: Nerve-sparing radical prostatectomy: evaluation of results after 250 patients. Journal of Urology 143(3): 538-544, 1990.
12. Catalona WJ, Basler JW: Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy. Journal of Urology 150(3): 905-907, 1993.
13. Lange PH, Reddy PK, Medini E, et al.: Radiation therapy as adjuvant treatment after radical prostatectomy. Journal of the National Cancer Institute Monographs 7: 141-149, 1988.
14. Ray GR, Bagshaw MA, Freiha F: External beam radiation salvage for residual or recurrent local tumor following radical prostatectomy. Journal of Urology 132(5): 926-930, 1984.
15. 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. Journal of Urology 142(5): 1266-1271, 1989.
16. 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. Journal of Urology 149(5): 1029-1034, 1993.
17. Stamey TA, Yang N, Hay AR, et al.: Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. New England Journal of Medicine 317(15): 909-916, 1987.
18. Hudson MA, Bahnson RR, Catalona WJ: Clinical use of prostate specific antigen in patients with prostate cancer. Journal of Urology 142(4): 1011-1017, 1989.
19. Paulson DF, Moul JW, Walther PJ: Radical prostatectomy for clinical stage T1-2N0M0 prostatic adenocarcinoma: long-term results. Journal of Urology 144: 1180-1184, 1990.
20. Wallner K, Roy J, Harrison L: Tumor control and morbidity following transperineal iodine 125 implantation for stage T1/T2 prostatic carcinoma. Journal of Clinical Oncology 14(2): 449-453, 1996.
21. D'Amico AV, Coleman CN: Role of interstitial radiotherapy in the management of clinically organ-confined prostate cancer: the jury is still out. Journal of Clinical Oncology 14(1): 304-315, 1996.
22. 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): 442-453, 1997.
23. Kuban DA, El-Mahdi AM, Schellhammer PF: I-125 interstitial implantation for prostate cancer. What have we learned 10 years later? Cancer 63(12): 2415-2420, 1989.
24. 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. International Journal of Radiation Oncology, Biology, Physics 21(3): 537-547, 1991.
25. Hanks GE, Hanlon AL, Schultheiss TE, et al.: Dose escalation with 3D conformal treatment: five year outcomes, treatment optimization, and future directions. International Journal of Radiation Oncology, Biology, Physics 41(3): 501-510, 1998.
26. Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostatic cancer. Summary, Evidence Report/Technology Assessment: Number 4, January 1999. Agency for Health Care Policy and Research, Rockville, MD. Available at: http://www.ahcpr.gov/clinic/prossumm.htm. Accessed 6/14/99.
27. Walsh PC: Radical prostatectomy. In: Walsh PC, Gittes RF, Perlmutter AD, et al., Eds.: Campbell's Urology. Philadelphia: W.B. Saunders, 5th ed., 1986, pp 2754-2775.
28. Paulson DF, Lin GH, Hinshaw W, et al.: Radical surgery versus radiotherapy for adenocarcinoma of the prostate. Journal of Urology 128(3): 502-504, 1982.
29. Witjes WP, Schulman CC, Debruyne FM: Preliminary results of a prospective randomized study comparing radical prostatectomy versus radical prostatectomy associated with neoadjuvant hormonal combination therapy in T2-3 N0 M0 prostatic carcinoma. Urology 49(Suppl 3A): 65-69, 1997.
30. Fair WR, Cookson MS, Stroumbakis N, et al.: The indications, rationale, and results of neoadjuvant androgen deprivation in the treatment of prostatic cancer: Memorial Sloan-Kettering Cancer Center results. Urology 49(Suppl 3A): 46-55, 1997.
31. Bazinet M, Zheng W, Begin LR, et al.: Morphologic changes induced by neoadjuvant androgen ablation may result in underdetection of positive surgical margins and capsular involvement by prostatic adenocarcinoma. Urology 49(5): 721-725, 1997.
32. Perez CA, Garcia D, Simpson JR, et al.: Factors influencing outcome of definitive radiotherapy for localized carcinoma of the prostate. Radiotherapy and Oncology 16(1): 1-21, 1989.
33. Blasko JC, Wallner K, Grimm PD, et al.: Prostate specific antigen based disease control following ultrasound guided iodine-125 implantation for stage T1/T2 prostatic carcinoma. Journal of Urology 154(3): 1096-1099, 1995.
34. Shinohara K, Connolly JA, Presti JC, et al.: Cryosurgical treatment of localized prostate cancer (stages T1 to T4): preliminary results. Journal of Urology 156(1): 115-121, 1996.
35. Fair WR, Cookson MS, Stroumbakis N, et al.: Update on neoadjuvant androgen deprivation therapy (ADT) and radical prostatectomy in localized prostate cancer. Proceedings of the American Urological Association 155(Suppl): A-1426, 667A, 1996.
36. Soloway MS, Sharifi R, Wajsman Z, et al.: Randomized prospective study: radical prostatectomy alone vs radical prostatectomy preceded by androgen blockade in cT2b prostate cancer - initial results. Proceedings of the American Urological Association 155(Suppl): A-976, 555A, 1996.

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