martes, 24 de septiembre de 2019

Prostate Cancer Treatment (PDQ®) 4/8 –Health Professional Version - National Cancer Institute

Prostate Cancer Treatment (PDQ®)–Health Professional Version - National Cancer Institute

National Cancer Institute

Prostate Cancer Treatment (PDQ®)–Health Professional Version

Stage I Prostate Cancer Treatment

Overview

Stage I prostate cancer is defined by the American Joint Committee on Cancer's TNM (tumor, node, metastasis) classification system:[1]
  • cT1a–c, N0, M0, prostate-specific antigen (PSA) <10 ng/mL, Gleason ≤6.
  • cT2a, N0, M0, PSA <10 ng/mL, Gleason ≤6.
  • pT2, N0, M0, PSA <10 ng/mL, Gleason ≤6.
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.[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), interstitial implantation of radioisotopes, and watchful waiting and active surveillance/active monitoring 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]

Standard Treatment Options for Stage I Prostate Cancer

Standard treatment options for patients with stage I prostate cancer include the following:
  1. Watchful waiting or active surveillance/active monitoring.
  2. Radical prostatectomy.
  3. External-beam radiation therapy (EBRT).
  4. Interstitial implantation of radioisotopes.

Watchful waiting or active surveillance/active monitoring

Asymptomatic patients of advanced age or with concomitant illness may warrant consideration of careful observation without immediate active treatment.[4-6] Watch and wait, observation, expectant management, and active surveillance/active monitoring are terms indicating a strategy that does not employ immediate therapy with curative intent. (Refer to the Watchful Waiting or Active Surveillance/Active Monitoring section in the Treatment Option Overview for Prostate Cancer section of this summary for more information.)
Evidence (observation with delayed hormonal therapy):
  1. In a retrospective pooled analysis, 828 men with clinically localized prostate cancer were managed by initial conservative therapy with subsequent hormonal 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.[4]

Radical prostatectomy

Radical prostatectomy, usually with pelvic lymphadenectomy (with or without the nerve-sparing technique designed to preserve potency) is the most commonly applied therapy with curative intent.[7-9] Radical prostatectomy may be difficult after a transurethral resection of the prostate (TURP).
Because about 40% to 50% of men with clinically organ-confined disease are found to have pathologic extension beyond the prostate capsule or surgical margins, the role of postprostatectomy adjuvant radiation therapy has been studied.
Consideration may also be given to postoperative radiation therapy (PORT) for patients who are found to have seminal vesicle invasion by tumor at the time of prostatectomy or who have a detectable level of PSA more than 3 weeks after surgery.[10-12] Because duration of follow-up in available studies is still relatively short, the value of PORT is yet to be determined; however, PORT does reduce local recurrence.[10] Careful treatment planning is necessary to avoid morbidity.
Evidence (radical prostatectomy followed by radiation therapy):
  1. In a randomized trial of 425 men with pathologic T3, N0, and M0 disease, postsurgical EBRT (60–64 Gy to the prostatic fossa over 30–32 fractions) was compared with observation.[11][Level of evidence: 1iiA]
    • The primary endpoint, metastasis-free survival, could be affected by serial PSA monitoring and resulting metastatic work-up for PSA increase. This could have biased the primary endpoint in favor of radiation therapy, which was associated with a lower rate of PSA rise. Nevertheless, metastasis-free survival was not statistically different between the two study arms (P = .06). After a median follow-up of about 10.6 years, the overall median survival was 14.7 years in the radiation therapy group versus 13.8 years in the observation group (P = .16).
    • Although the OS rates were not statistically different, complication rates were substantially higher in the radiation therapy group: overall complications were 23.8% versus 11.9%, rectal complications were 3.3% versus 0%, and urethral stricture was 17.8% versus 9.5%.
    • After a median follow-up of about 12.5 years, however, OS was better in the radiation therapy arm; hazard ratio (HR)death, 0.72 (95% confidence interval [CI], 0.55–0.96; P = .023). The 10-year estimated survival rates were 74% in the radiation therapy arm and 66% in the control arm. The 10-year estimated metastasis-free survivals were 73% and 65% (P = .016).[12][Level of evidence: 1iiA]
  2. Another randomized trial came to a different conclusion with respect to the effect of postoperative radiation therapy on OS.[13][Level of evidence: 1iiA] In the European Organization for Research and Treatment of Cancer (EORTC) trial (EORTC-22911 [NCT00002511]), 1,005 men aged 75 years and younger with clinical T0 to T3 prostate cancer were randomly assigned after prostatectomy to receive PORT (60 Gy) or observation, with subsequent therapy delayed until the occurrence of either biochemical or clinical relapse. The recommended treatment for local recurrence was radiation.
    • With a median follow-up of 10.6 years (up to 16.6 years), the biochemical progression-free survival (PFS) rates were higher in the observation study arm (60.6% vs. 41.1%; HR, 0.49; 95% CI, 0.41–0.59; P < .0001). Locoregional relapse rates were 8.4% versus 17.3% in favor of immediate radiation (HR, 0.45; 95% CI, 0.32–0.68; P < .0001).
    • However, the large differences in biochemical relapse-free survival and local recurrence did not translate into an advantage in either distant metastasis (11.0% vs. 11.3%; HR, 0.99; 95% CI, 0.67–1.44; P = .94) or in OS (76.9% with immediate radiation vs. 80.7% with observation; HR, 1.18; 95% CI, 0.91–1.53; P = .2). Nor was there a difference in prostate– cancer-specific mortality (3.9% vs. 5.2%; HR, 0.78; 95% CI, 0.46–1.33; P = .34)
    • The 10-year cumulative risk of severe (grade 3) late toxicity in the immediate radiation study group was 5.3% versus 2.5% in the observation group (P = .052). Late adverse effects of any grade were also higher in the immediate radiation group (70.8% vs. 59.7%; P = .001).
Radical prostatectomy has been compared with watchful waiting or active surveillance/active monitoring. (Refer to the Radical prostatectomy compared with other treatment options section in the Treatment Option Overview for Prostate Cancer section of this summary for more information about radical prostatectomy compared with watchful waiting or active surveillance/active monitoring.)
Evidence (radical prostatectomy compared with watchful waiting):
  1. The Prostate Intervention Versus Observation Trial (PIVOT-1 or VA-CSP-407 [NCT00002606]) is a randomized trial conducted in the PSA screening era that directly compared radical prostatectomy with watchful waiting. From November 1994 through January 2002, 731 men aged 75 years or younger with localized prostate cancer (stage T1–2, NX, M0, with a blood PSA <50 ng/mL) and a life expectancy of at least 10 years were randomly assigned to radical prostatectomy versus watchful waiting.[14-16][Levels of evidence: 1iiA, 1iiB]
    • About 50% of the men had nonpalpable, screen-detected disease.
    • After a median follow-up of 12.7 years (range up to about 19.5 years), the all-cause mortality was 61.3% versus 66.8% in the prostatectomy and watchful-waiting study arms, respectively, an absolute difference of 5.5 percentage points (95% CI -1.5 to 12.4) that was not statistically significant (HR, 0.84; 95% CI, 0.70–1.01). Prostate–cancer-specific mortality was 7.4% versus 11.4%, and it also was not statistically significant (HR, 0.63; 95% CI, 0.3–1.02).
    • Although treatment for disease progression was given more frequently in the observation arm of the study, most of the treatment was for asymptomatic, local, or biochemical (PSA) progression.
    • As expected, urinary incontinence and erectile/sexual dysfunction was more common in the prostatectomy group for at least 10 years of follow-up. Absolute differences in patient-reported use of absorbent urinary pads was greater in the surgery group by more than 30 percentage points at all time points for at least 10 years. Disease- or treatment-related limitations in activities of daily living were worse with surgery than with observation through 2 years, but then were similar in both study arms.

External-beam radiation therapy (EBRT)

EBRT is another treatment option used with curative intent.[17-21] Definitive radiation therapy should be delayed 4 to 6 weeks after TURP to reduce the incidence of stricture.[22] Adjuvant hormonal therapy should be considered for patients with bulky T2b to T2c tumors.[23,24]
Evidence (EBRT with or without adjuvant hormonal therapy):
  1. Radiation Therapy Oncology Group's (RTOG) trial 7706 (RTOG-7706).[25][Level of evidence: 1iiA]
    • Prophylactic radiation therapy to clinically or pathologically uninvolved pelvic lymph nodes does not appear to improve OS or prostate cancer-specific survival.
  2. RTOG-9413 (RTOG-9413 [NCT00769548]) trial.[26]; [27][Level of evidence: 1iiDiii]
    • Although RTOG-9413 showed increased PFS at 4 years for patients who had a 15% estimated risk of lymph node involvement and received whole-pelvic radiation therapy compared with prostate-only radiation therapy, OS and PSA failure rates were not significantly different.
  3. In a randomized trial, 875 men with locally advanced nonmetastatic prostate cancer (T1b–T2 moderately or poorly differentiated tumors; T3 tumors of any grade) were randomly assigned to receive 3 months of a luteinizing hormone-releasing hormone agonist plus long-term flutamide (250 mg PO tid) with or without EBRT.[24][Level of evidence: 1iiA]
    • Nineteen percent of the men had tumor stage T2, and 78% of the men had T3. At 10 years, both overall mortality (29.6% vs. 39.4%; 95% CI for the difference, 0.8%–18.8%) and the prostate–cancer-specific mortality (11.9% vs. 23.9%; 95% CI for the difference, 4.9%–19.1%) favored combined hormonal and radiation therapy.
    • Although flutamide might not be considered a standard hormonal monotherapy in the setting of T2 or T3 tumors, radiation therapy provided a disease-free survival or tumor-specific survival advantage even though this monotherapy was applied. This analysis rests on the assumption that flutamide does not shorten life expectancy and cancer-specific survival. Radiation therapy was not delivered by current standards of dose and technique.

Interstitial implantation of radioisotopes

Interstitial implantation of radioisotopes (i.e., iodine I 125 [125I], palladium, and iridium Ir 192) done through a transperineal technique with either ultrasound or computed-tomography guidance, is being used in patients with T1 or T2a tumors. Short-term results in these patients are similar to those for radical prostatectomy or EBRT.[28,29]; [30][Level of evidence: 3iiiDiv]
Factors for consideration in the use of interstitial implants include the following:
  • 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%.[28,30] In contrast, rates of maintenance of sexual potency with radical prostatectomy were 10% to 40% and 40% to 60% with EBRT.
  • Typical side effects from interstitial implants that subside with time include urinary tract frequency, urgency, and less commonly, urinary retention.
  • 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 the implant technique.[28]
Long-term follow-up of these patients is necessary to assess treatment efficacy and side effects.
Retropubic freehand implantation with 125I has been associated with an increased local failure and complication rate [31,32] and is now rarely done.

Treatment Options Under Clinical Evaluation for Stage I Prostate Cancer

Treatment options under clinical evaluation for patients with stage I prostate cancer include the following:
  1. High-intensity focused ultrasound therapy.[33-36]
  2. Photodynamic therapy.

Photodynamic therapy

Vascular-targeted photodynamic therapy using a photosensitizing agent has been tested in men with low-risk prostate cancer. In the CLIN1001 PCM301 (NCT01310894) randomized trial, 413 men with low-risk cancer (tumor stage T1–T2c, PSA ≤10 ng/mL, generally Gleason score 3 + 3) were randomly assigned in an open-label trial to receive either the photosensitizing agent, padeliporfin (4 mg/kg intravenously [IV] over 10 minutes, and optical fibers inserted into the target area of the prostate, then activated by 753 nm laser light at 150 mW/cm for 22 minutes 15 seconds), or active surveillance.[37] Median time to local disease progression was 28.3 months for patients receiving padeliporfin and 14.1 months for patients who were assigned to active surveillance (HR, 0.34; 95% CI, 0.24–0.46; P < .0001).[37][Level of evidence: 1iiDiii] However, the appropriate population for photodynamic therapy may be quite narrow, as it may overtreat men with very low-risk disease and undertreat men with higher-risk disease.[38]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
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  2. Consensus conference. The management of clinically localized prostate cancer. JAMA 258 (19): 2727-30, 1987. [PUBMED Abstract]
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  4. 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]
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  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. 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]
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  12. Thompson IM, Tangen CM, Paradelo J, et al.: Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 181 (3): 956-62, 2009. [PUBMED Abstract]
  13. Bolla M, van Poppel H, Collette L, et al.: Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet 366 (9485): 572-8, 2005 Aug 13-19. [PUBMED Abstract]
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  25. 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. Int J Radiat Oncol Biol Phys 40 (4): 769-82, 1998. [PUBMED Abstract]
  26. Roach M, DeSilvio M, Lawton C, et al.: Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol 21 (10): 1904-11, 2003. [PUBMED Abstract]
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