Radiation Oncology/Prostate/Natural History

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Prostate: Main Page | Prostate Overview | Screening and Prevention | Workup | Natural History | External Beam RT | IMRT | Androgen Suppression Therapy | Brachytherapy | Protons | Prostatectomy | Adjuvant RT after Prostatectomy | Salvage RT | Chemotherapy | Localized prostate cancer | Node Positive | Advanced disease | Recurrence after RT | Cryotherapy | RTOG Prostate Trials | Randomized Evidence


  • Traditionally, watchful waiting was defined as no treatment until disease progression to symptomatic locally advanced or metastatic disease. Palliative treatment was with androgen ablation therapy
  • In the PSA era, patients managed with watchful waiting are sometimes still monitored with periodic PSA testing. This may allow intervention at a future time
  • Active surveillance is being evaluated as a strategy to monitor patients with low risk disease with serial PSA (PSA-DT) and repeat biopsies, and actively intercede with a curative intervention (RP or RT) as necessary


Contents

[edit] Watchful waiting

  • Watchful waiting/deferred treatment may be a reasonable option for some patients with early stage PCA, particularly if their life expectancy is <10 years. The 10-year disease-specific survival is ~85% for patients with localized PCA. The studies linked above were performed with patients diagnosed in pre-PSA era. Randomized multi-institutional trials are sadly lacking.
  • Radical prostatectomy reduces overall mortality slightly (by 6% at 10 years), and disease-specific mortality, risk of mets and local progression significantly when compared with watchful waiting. This benefit may be limited to patients <65 years of age, and should be explored further. However, in the Swedish trial below, most men had palpable (T2) cancer while most men in North America have T1c disease. It is not clear how generalizable these results are to a current patient population, and whether RP would still be significantly better over these time-frames.


[edit] Cohort Studies

  • Connecticut Tumor Registry (1971-84)
    • Retrospective cohort study. 767 patients. Clinically localized. Treated with observation or immediate or delayed hormonal therapy.
    • 20-years; 2005 PMID 15870412 — "20-year outcomes following conservative management of clinically localized prostate cancer." Albertsen PC et al. JAMA. 2005 May 4;293(17):2095-101.
      • Mortality rate: 3.3% per year during first 15 years, then 1.8% per year thereafter. Low grade (GS 2-4) 0.6% per year, high grade (GS 8-10) 12% per year
      • Conclusion: Low risk of dying from prostate cancer for low risk group (Gleason 2-4). High risk of dying within 10 years for Gleason 8-10. Intermediate for Gleason 5-6. Mortality risk does not support aggressive treatment for localized low-grade PCA
      • Comment PMID 15870419: Relatively low grade disease (33% GS <=5 compared with ~5% in contemporary series), many s/p TURP (which is effectively a prophylactic partial prostatectomy, and decreases death rate from PCA), many with serious chronic illness (which is seen less often with earlier PSA-based detection, and who would be expected to die of competing causes)
  • Sweden (1977-1984)
    • 15-years; 1997 PMID 9020270 — "Fifteen-year survival in prostate cancer. A prospective, population-based study in Sweden." (Johansson JE, JAMA. 1997 Feb 12;277(6):467-71.)
      • Population based study in one county of Sweden. No screening. 642 pts diagnosed between 1977-1984 with follow up to 1994. Mean age 72. 33% had T1a disease and 2/3 were low grade. Hormone treatment with disease progression
      • Prostate cancer accounted for 37% of deaths.
      • T0-T2: 15-year survival was 81%, regardless of initial or deferred treatment. 11% died of PCA
      • Stage III: 15-year survival was 57%; Stage IV: 15-year survival was 6%
      • Conclusion: "Patients with localized prostate cancer have a favorable outlook following watchful waiting, and the number of deaths potentially avoidable by radical initial treatment is limited. Without reliable prognostic indicators, an aggressive approach to all patients with early disease would entail substantial overtreatment. In contrast, patients with locally advanced or metastatic disease need trials of aggressive therapy to improve their poor prognosis. "
    • 10-years; 1992 PMID 1556796 — High 10-year survival rate in patients with early, untreated prostatic cancer. (Johansson JE, JAMA. 1992 Apr 22-29;267(16):2191-6.
  • Denmark, 1997, (1979-83)- PMID 9307192 - "The natural history of prostate carcinoma based on a Danish population treated with no intent to cure." (Borre M, Cancer. 1997 Sep 1;80(5):917-28.
    • Population based study in a single county. No screening. 719 cases. 15 year median f/u. 45% diagnosed incidentally. 31% organ confined. 62% died of prostate cancer.
    • Disease specific survival 80% at 1-yr, 38% at 5-yrs, 17% at 10-yrs.
  • Karolinska, 1997 PMID 9372882 -- "Deferred treatment of clinically localized low-grade prostate cancer: actual 10-year and projected 15-year follow-up of the Karolinska series." (Adolfsson J, Urology. 1997 Nov;50(5):722-6.)
    • 122 patients with palpable, clinically localized, low-grade prostate cancer diagnosed from 1978 to 1982
    • 10-year DFS 90%; 15-year DFS 75%
    • No antitumoral therapy had been given to 58 (48%) patients at follow-up or before death. The chance of being untreated 5 and 10 years after diagnosis, if still alive, was 71% and 43%, respectively
    • Conclusion: "Our data are mature up to 10 years of observation and, based on these data, deferred treatment is a valid option for patients with clinically localized low-grade prostate cancer with a life expectancy of 10 years or less. The data are not definitive beyond 10 years and firm conclusions will be speculative, but our findings indicate that there probably is room for efficacious local treatment in patients with localized prostate cancer and a life expectancy longer than 10 years."


Meta-analyses

  • Meta-analysis, 1998 - PMID 9554328 -- An analysis of watchful waiting for clinically localized prostate cancer. (Steinberg GD, J Urol 1998; 159:1431-6.)
    • Conclusion: "Watchful waiting is probably the best treatment option for men with well and perhaps moderately differentiated, low volume prostate cancer who have a life expectancy of less than 10 years. However, the conclusions derived from watchful waiting studies of older men cannot and should not be applied to younger, healthier men or to those with more advanced or aggressive disease. If treated ineffectively, many of these men will die of prostate cancer. CONCLUSIONS: Most men with prostate cancer who have a life expectancy greater than 10 to 15 years should be treated with curative intent."
  • Meta-analysis, 1994 - PMID 8272085 — Results of conservative management of clinically localized prostate cancer. (Chodak GW, N Engl J Med. 1994 Jan 27;330(4):242-8.
    • Meta-analysis from six nonrandomized studies of 828 pts treated conservatively for localized prostate cancer.
    • 10-year disease specific survival was 87% for grade 1 or 2 tumors, 34% for grade 3 (out of 3). **Metastasis free survival (censoring deaths from other causes) was 81%, 58%, 26%, respectively for each grade.
    • Conclusion: "The strategy of initial conservative management and delayed hormone therapy is a reasonable choice for some men with grade 1 or 2 clinically localized prostate cancer, particularly for those who have an average life expectancy of 10 years or less. New treatment strategies are needed for men with grade 3 prostate cancer."
  • Meta-analysis, 1993 PMID 8319164 -- Recent results of management of palpable clinically localized prostate cancer. (Adolfsson J, Cancer. 1993 Jul 15;72(2):310-22.)
    • Literature review for localized cancer studies since 1980
    • 10-year DFS was 93% for radical prostatectomy, 83% for deferred treatment, and 62% for external radiation therapy.
    • Conclusion: "As judged from our analysis, clinically localized prostate cancer often has a protracted course associated with a significant competing mortality and marginal benefit from radical prostatectomy at 10 years in terms of the endpoints used."

[edit] Watchful waiting vs. Radical Treatment

  • SEER study, 2006 (1991-99) - PMID 17164454 — "Survival associated with treatment vs observation of localized prostate cancer in elderly men." Wong YN et al. JAMA. 2006 Dec 13;296(22):2683-93.
    • 44,000 men (age 65-80) from SEER database, diagnosed in 1991-99 with organ-confined low or intermediate grade prostate cancer. Defined treatment as RT or prostatectomy (but not hormones) and observation as not having had RT, surgery, or hormones. 32,000 had treatment, 12,000 observation. 12 year study period.
    • 37% in obs group died vs 23% in treatment group. HR=0.69 for treatment. Benefit seen in all subgroups, including older men age 75-80.
    • Conclusion: suggestion that active treatment leads to improved survival for low to intermediate risk prostate cancer. Potential for selection bias exists.

[edit] Watchful Waiting vs. Prostatectomy

  • VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT) (1994-2002) -- radical prostatectomy vs watchful waiting
    • Randomized. 731 men. clinicaltrials.gov entry
    • 1997 PMID 9268976 -- "The Prostate Cancer Intervention Versus Observation Trial (PIVOT)." (Wilt TJ, Oncology (Williston Park). 1997 Aug;11(8):1133-9; discussion 1139-40, 1143.)
      • Overview of trial. Conducted at VA and NCI medical centers. Primary outcome all-cause mortality. Secondary outcomes prostate cancer- and treatment-specific morbidity and mortality, health status, predictors of disease-specific outcomes, and cost-effectiveness.
    • 2009 PMID 18783735 -- "The Prostate cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer." (Wilt TJ, Contemp Clin Trials. 2009 Jan;30(1):81-7. Epub 2008 Aug 23.)
      • Study overview. 13,022 men screened; 5,023 met eligibility criteria; 731 agreed to participate and were randomized.
      • Description: Mean age 67 years. Median PSA 7.8 ng/ml. Low risk 43%, intermediate risk 36%, high risk 20%. Predominately detected by rising PSA
      • Conclusion: Diverse population representative of men diagnosed with PCA in United States
  • Scandinavian SPCG-4 (1989-99) - prostatectomy vs watchful waiting
    • Randomized. 695 men, early prostate cancer (T1-T2), biopsy proven. No adjuvant treatment. If symptomatic local progression, treated with orchidectomy or GnRH analog. Clinical follow-up with PSA, exam. Cause of death scored as due to prostate cancer (if progressive distant mets) or due to other causes. 75% had T2 tumors.
    • QoL; 2002 PMID 12226149 -- "Quality of life after radical prostatectomy or watchful waiting." (Steineck G, N Engl J Med. 2002 Sep 12;347(11):790-6.)
      • 326/376 Swedish patients randomized 1989-1996. Mean F/U 4 years
      • Symptoms:
        • Worse after RP: erectile dysfunction (80% vs. 45%); urinary leakage (49% vs. 21%)
        • Worse after observation: urinary obstruction (28% vs. 44%)
        • No difference: bowel function, anxiety, depression, well-being, quality-of-life
      • Conclusion: Different risks, but no influence on well-being or subjective quality of life
    • 6-years; 2002 PMID 12226148 — "A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer." Holmberg L et al. N Engl J Med. 2002 Sep 12;347(11):781-9.
      • Mean f/u 6.2 yrs. 115 deaths: 47 deaths due to prostate cancer (31 watchful waiting, WW; 16 radical prostatectomy, RP). With RP, 2% decrease risk of death due to prostate cancer at 5 years, 6.6% at 8 years. Hazard ratio 0.5. Risk of distant mets: 14% difference at 8 years (HR=0.63). Required hormones: 24% (WW) vs 17%. No overall survival difference.
    • 8-years; 2005 PMID 15888698 — "Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer" Bill-Axelson A et al. N Engl J Med. 2005 May 12;Volume 352(19):1977-1984. Median 8.2 yrs f/u.
      • Outcome: 10-year OS RP 91% vs. WW 86% (RR=0.74, SS), 10-year DFS 90% vs. 85% (SS), 10-year DMFS 85% vs. 75% (SS), 10-year LC 81% vs. 56% (SS)
      • Conclusion: Treatment of prostate cancer results in 5% fewer cancer related deaths and 5% fewer overall deaths. May not apply to modern era with PSA screening due to lag time and stage migration.
    • 11-years; 2008 PMID 18695132 -- "Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial." (Bill-Axelson A, J Natl Cancer Inst. 2008 Aug 20;100(16):1144-54. Epub 2008 Aug 11.) Median F/U 10.8 years (3 weeks - 17.2 years)
      • Outcome: 12-year death due to PCA surgery 12% vs. observation 18% (SS); 12-year DM rate 19% vs. 26% (SS). For surgery, if ECE+ PCA death rate 14x higher than if ECE-
      • Conclusion: RP reduces PCA mortality, with little or no further increase in benefit 10+ years after surgery
  • VACURG (1967-1975) -- prostatectomy vs. watchful waiting
    • Randomized. 111/142 patients, prostate cancer Tis-T2, no palpable tumor, no pelvic staging prior to randomization. Arm 1) Radical prostatectomy vs. Arm 2) Placebo
    • 1988 PMID 3187435 -- "Treatment of localized prostatic cancer. Radical prostatectomy versus placebo. A 15-year follow-up." (Madsen PO, Scand J Urol Nephrol Suppl. 1988;110:95-100.)
      • Outcome:
        • Stage I: 5-year OS RP 87% vs. placebo 67%, 10-years 48% vs. 43%, 15-years 23% vs. 13%
        • Stage II: 5-year RP 92% vs. placebo 90% , 10-years 37% vs 55%, 15-years 17% vs. 20%
      • Conclusion: No significant difference in cummulative survival, either by Stage or overall
    • 1995 PMID 8578259 -- "Radical prostatectomy versus expectant treatment for early carcinoma of the prostate. Twenty-three year follow-up of a prospective randomized study" (Iversen P, Scand J Urol Nephrol Suppl. 1995;172:65-72.) Median F/U 23 years
      • Outcome: OS in favor of RP, but after adjustment for imbalances, no difference in either stage or both stages combined
      • Conclusion: Small sample size and limited statistical power
    • Comment: "Although the rate of mortality from prostate cancer was similar in the two groups, methodologic flaws make the conclusions of this study suspect." (Chodak, NEJM 1994)

[edit] Active Surveillance

  • Individualized management of early prostate cancer
    • Men with significant cancer are offered curative treatment
    • Men with low risk disease are actively monitored with serial PSA and repeat prostate biopsies. Decision to continue AS or undergo curative treatment is individualized
      • Initial entry criteria are typically those for low risk disease: cT1-T2, GS <=6 (sometimes <=7), PSA <10 (sometimes PSA <15 or <20), low PSA velocity (PSA DT >4 years)
      • Surveillance strategies have not been refined yet
      • Action thresholds have also not yet been well defined


  • Toronto (1995-2002)
    • Phase II. 450 patients. Initial criteria favorable disease (T1b-T2b, GS 6, PSA <10) or patients >70 intermediate disease (PSA <15 or GS 7). In 1999 ammended to include only favorable disease. Intermediate risk (T3, PSA >15, GS 7) in 19%. Monitored with PSA every 3 months x2 years then 6 months, and repeat biopsy at 6-12 months and then 3-4 years. Initial decision made after 6 months and 3 PSAs to calculate PSA-DT. Trigger for treatment: PSA-DT <3 years, progression to GS 7, or clinical progression (prostate nodule)
    • 2009 PMID 19917860 -- "Clinical Results of Long-Term Follow-Up of a Large, Active Surveillance Cohort With Localized Prostate Cancer." (Klotz L, J Clin Oncol. 2009 Nov 16. [Epub ahead of print]) Median F/U 6.8 years
      • Outcome: OS 79%; 10-year OS 68%, but 10-year CSS 97%, bPFS 87%. Overall, 30% of patients were reclassified as higher risk and offered definitive therapy (RT+/-ADT 67%, ADT alone 7%, surgery 26%). Predictors for treatment T2, GS >6. All PCA-mortality (n=5) was in men reclassified as higher risk
      • Radical treatment (n=117): PSA failure 50%. PSA-DT <3 predictive for death
      • Conclusion: Low rate of prostate cancer PSA failure (13%) and mortality (3%). Among patient reclassified, PSA failure in 50%
    • 2006 PMID 16414494 -- "Active surveillance with selective delayed intervention for favorable risk prostate cancer." (Klotz L, Urol Oncol. 2006 Jan-Feb;24(1):46-50.)
      • 299 patients analyzed.
      • 8-year outcome: 65% free of treatment; DSS 99%
      • Conclusion: AS with selective delayed intervention is a practical middle ground between radical therapy for all and watchful waiting
    • 2006 PMID 16952640 -- "Modeling prostate specific antigen kinetics in patients on active surveillance." (Zhang L, J Urol. 2006 Oct;176(4 Pt 1):1392-7; discussion 1397-8.)
      • 231 patients analyzed
      • Outcome: 40% high risk of progression, 60% low risk of progression. Model developed
      • Conclusion: Rational decision can be recommended ~2.3 years after initially surveillance
    • 2004 PMID 15003150 -- "Comparison of histologic grade between initial and follow-up biopsy in untreated, low to intermediate grade, localized prostate cancer." (Choo R, Can J Urol. 2004 Feb;11(1):2118-24.)
      • 123 patients. 67/123 with repeat biopsy. Median time-to-biopsy 22 months
      • Gleason score: upgraded 28%, same 30%, downgraded 40%; 31% no malignancy
      • Conclusion: No consistent histologic upgrade on rebiopsy
    • 2004 PMID 15535443 -- "Active surveillance with selective delayed intervention: using natural history to guide treatment in good risk prostate cancer." (Klotz L, J Urol. 2004 Nov;172(5 Pt 2):S48-50; discussion S50-1.)
      • PSA-DT: Median 7.0 years, 35% >10 years
      • 8-year outcome: OS 85%, DSS 99%
      • Conclusion: Practical approach; longer F/U necessary to confirm in men with >15 year life expectancy
    • 2001 PMID 11395227 -- "PSA doubling time of prostate carcinoma managed with watchful observation alone." (Choo R, Int J Radiat Oncol Biol Phys. 2001 Jul 1;50(3):615-20.)
      • 134 patients analyzed. Median F/U 2 years. Median PSA at enrollment 6.3
      • PSA-DT: <2 years 14%, 2-5 years 34%, 5-10 years 19%, 10-20 years 8%, 20-50 years 5%, >50 years 20%; median PSA-DT 5.1 years. No correaltion with age, cT-stage, GS, or initial PSA
      • Conclusion: PSA-DT varies widely in untreated PCA; may be useful in watchful observation
  • Dutch PRIAS trial
    • Prospective observational study. Protocol. Expected enrollment >900. Patients with T1c-T2, PSA <=10, PSA density <0.2, GS <7. Follow up with PSA every 3 months, rebiopsy at 12 months
    • 2009 (2006-2008) PMID 19817747 -- "Short-term outcomes of the prospective multicentre 'Prostate Cancer Research International: Active Surveillance' study." (van den Bergh RC, BJU Int. 2009 Oct 8. [Epub ahead of print])
      • First 500 patients. Median F/U 1 year
      • Outcome: 2-year continued AS rate 73%. Rebiopsy no cancer 34%, GS 2-6 44%, GS 7+ 22%. After RP (n=24), T3 disease in 17%, GS 7+ in 50%
      • Conclusion: Active surveillance seems feasible
    • 2009 PMID 19637245 -- "Anxiety and distress during active surveillance for early prostate cancer." (van den Bergh RC, Cancer. 2009 Sep 1;115(17):3868-78.)
      • Prospective. 150 patients on prospective AS protocol, asked to fill an anxiety/distress questionnaire (decisional conflict, depression, generic anxiety, PCA-specific anxiety). Compared with reference values. Response rate 86% (n=129).
      • Outcome: Better scores than reference in decisional conflict 89%, depression 92%, generic anxiety 83%, PCA-specific anxiety 93%. Scores comparable/better than literature reports for active treatment for PCA
      • Multivariate analysis: neurotic personality score and higher PSA predicted for PCA-specific anxiety
      • Conclusion: Men on AS proton reported favorable levelsof anxiety and distress, except for neurotic personality types
    • 2009 PMID 19594731 -- "Disease insight and treatment perception of men on active surveillance for early prostate cancer." (van den Bergh RC, BJU Int. 2009 Jul 7. [Epub ahead of print])
      • 150 patients on prospective AS protocol, asked to fill a general knowledge of PCA questionnaire. Response rate 86% (n=129)
      • Outcome: Correct answers to median 13/15 knowledge questions (87%). Younger and higher educated men higher scores. Reported AS benefit: delay of side-effects. Reported downside: risk of disease progression. Specific negative experiences included feeling of loss of control over treatment decisions, desire for more active participation in disease management, and distress at follow up visits
      • Conclusion: Adequate knowledge of prostate cancer and realistic perception of AS was identified
  • Johns Hopkins
    • Prospective longitudinal surveillance. 470 men, median age 66 years, T1c, small volume prostate cancer. Annual repeat bx. Progression if Gleason pattern 4/5, >50% on any one core, >2 cores.
    • 2007 PMID 17936806 -- "Expectant management of prostate cancer with curative intent: an update of the Johns Hopkins experience." (Carter HB, J Urol. 2007 Dec;178(6):2359-64; discussion 2364-5. Epub 2007 Oct 22.) Median F/U 2.8 years
      • Outcome: Continued AS in 59%. Curative intervention in 25% at median 2.2 years
      • Conclusion: Active surveillance may be a rational alternative to active treatment
    • 2009 PMID 19758635 -- "Radical prostatectomy findings in patients in whom active surveillance of prostate cancer fails." (Duffield AS, J Urol. 2009 Nov;182(5):2274-8. Epub 2009 Sep 16.)
      • Outcome: RP in 11% (n=51). Average time-to-RP 2.5 years. Organ-confined 65%, extra-prostatic extension 35%, SV/LN+ 5%, SM+ 15%. All tumors with dominant nodule >1 cm3 (n=10) located anteriorly
      • Conclusion: Most progression after AS occurs in 1-2 years, suggesting undersampling on initial biopsy. Most progression tumors have favorable patholody. Anterior regional should be sampled on biopsy
  • Eindhoven, The Netherlands; 2009 (1994-1998) PMID 19747357 -- "Prostate cancer survivors who would be eligible for active surveillance but were either treated with radiotherapy or managed expectantly: comparisons on long-term quality of life and symptom burden." (Thong MS, BJU Int. 2009 Aug 28. [Epub ahead of print])
    • Retrospective population-based registry. 142 patients. 71 men managed with AD matched to 71 survivors managed with RT. Health-related QoL (HRQL) data collected 5-10 years after diagnosis
    • Outcome: HRQL mostly comparable. Patients treated with RT had worse bowel scores (SS), and erectile dysfunction (47% vs. 68%, SS)
    • Conclusion: Patients managed expectantly have comparable HRQL, and lower symptom burden
  • UCSF; 2008 PMID 18433013 -- "Active surveillance for the management of prostate cancer in a contemporary cohort." (Dall'Era MA, Cancer. 2008 Jun 15;112(12):2664-70.)
    • Retrospective. 321 patients with low risk PCA, initially undergoing active surveillance. Initial mean PSA 6.5. Median F/U 3.6 years (1-17).
    • AS Criteria: PSA <10 ng/ml, bx GS <=6, <33% bx cores, cT1-T2a. Surveillance: PSA and DRE q3-6 months, trans-rectal U/S q6-12 months, repeat prostate bx at 12-24 months. Disease progression: increase in re-bx GS, PSA velocity change >0.75 ng/ml
    • Outcome: 37% had progression (38% higher grade GS on re-bx, 26% high PSA velocity), 24% received treatment, median 3 years after diagnosis. Additional 13% with no progression elected to obtain treatment. DSS 100%
    • Conclusion: Select individuals may be candidates for active surveillance
  • Erasmus University, The Netherlands (1993-2006)
    • 2007 PMID 17161520 -- "Active surveillance for prostate cancers detected in three subsequent rounds of a screening trial: characteristics, PSA doubling times, and outcome." (Roemeling S, Eur Urol. 2007 May;51(5):1244-50; discussion 1251.)
      • Retrospective. 278 men. Median age 70, median PSA 3.6, 80% cT1c, 20% cT2. Median F/U 3.4 years
      • Outcome: 44% with PSA-DT >10 years. Deferred treatment in 29%. 8-year OS 89%, DSS 100%
      • Conclusion: Preliminary beneficial outcome
  • Royal Marsden; 2005 (1993-2002)
    • 2007 PMID 17550414 -- "Does active surveillance for men with localized prostate cancer carry psychological morbidity?" (Burnet KL, BJU Int. 2007 Sep;100(3):540-3.)
      • Prospective. 764 patients approached, 329 enrolled in psychological study (100 on AS, 229 radical treatment)
      • Outcome: 16% anxiety, 6% depression. Not associated with AS vs. active treatment. Associated with younger age, time from diagnosis
      • Conclusion: Active surveillance not associated with greater psychological distress
    • 2005 PMID 15839912 -- "Early outcomes of active surveillance for localized prostate cancer." (Hardie C, BJU Int. 2005 May;95(7):956-60.)
      • Prospective. 80 men, fit for radical treatment, cT1-2, PSA <=20, GS <=7. PSA and DRE done at 3-6 month intervals. Decision to continue AS based on rise of PSA. At same time, 32 patients managed by watchful waiting, with hormones for symptomatic progression. Median F/U 3.5 years
      • Outcome on AS: 80% remained under observation, 14% radical treatment, 6% died from other causes. No mets, no palliative hormones, no deaths from PCA. All radically treated patients remained bNED. Median PSA-DT 12 years
      • Outcome on WW: 62% remained under observation, 25% palliative hormones, 12% died, 3% from prostate cancer
      • Conclusion: Active surveillance feasible; marked contrast with watchful waiting
  • European Randomized Study of Prostate Cancer; 2007 (Sweden data) PMID 17013897 -- "PSA doubling time predicts the outcome after active surveillance in screening-detected prostate cancer: results from the European randomized study of screening for prostate cancer, Sweden section." (Ali K, Int J Cancer. 2007 Jan 1;120(1):170-4.)
    • Randomized. 10,000 men randomized to biennial PSA screening vs. control on 12/31/1994.
    • Outcome: Through 12/2004, 6.6% diagnosed with PCA. 41% managed with active surveillance
    • Patients on AS: 39% received treatment during follow-up (67% RP, 23% RT, 10% AST). PSA-DT <4 years predicted for relapse
    • Conclusion: optimal candidate for AS is early, low-grade, low-stage PCA with PSA-DT >4 years

[edit] Review

  • Erasmus; 2007 PMID 17364211 -- "Overdiagnosis and overtreatment of early detected prostate cancer." (Bangma CH, World J Urol. 2007 Mar;25(1):3-9.)
  • Toronto; 2006 PMID 16904052 -- "Active surveillance versus radical treatment for favorable-risk localized prostate cancer." (Klotz L, Curr Treat Options Oncol. 2006 Sep;7(5):355-62.)
    • Review. Calculate 73 patients needed-to-treat radically to save 1 PCA-related death
  • Midwest Urology; 2006 PMID 16402090 -- "Watchful waiting for prostate cancer: a review article." (Chodak GW, Prostate Cancer Prostatic Dis. 2006;9(1):25-9.)
  • Hopkins; 2005 PMID 16130016 -- "Expectant management: an option for localized prostate cancer." (Khan MA, Prostate Cancer Prostatic Dis. 2005;8(4):311-5.)
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