Watchful waiting and factors predictive of secondary treatment of localized prostate cancer

PURPOSE: Watchful waiting remains an important treatment option for some patients with localized prostate cancer. We defined the demographic, clinical and outcome features of men selecting watchful waiting as an initial treatment strategy, and determined factors predictive of eventual progression to secondary treatment. MATERIALS AND METHODS: Of 8390 patients diagnosed with prostate cancer from 1990 to 2001 in the Department of Defense Center for Prostate Disease Research Database, 1158 patients chose watchful waiting as initial treatment. The demographic and clinical differences between patients on watchful waiting and those choosing other initial treatments were compared using the chi-square test. Secondary treatment-free survival according to various prognostic factors was plotted using the Kaplan-Meier method and differences were tested using the log rank test. A multivariate Cox proportional hazards regression analysis was performed to determine which factors were independent predictors of secondary treatment. RESULTS: Compared to other patients, those selecting watchful waiting were older, had lower prostate specific antigen (PSA) at diagnosis, and were more likely to have lower stage (cT1) and lower grade (Gleason sum 7 or less) cancers. Age, PSA and clinical stage were all significant and independent predictors of secondary treatment. The relative risk of secondary treatment can be expressed as EXP (-0.034 x age at diagnosis + 0.284 x LOG (diagnostic PSA) + 0.271 x clinical stage T2 + 0.264 x clinical stage T3). CONCLUSIONS: Men who elect watchful waiting as initial management for prostate cancer are older with lower Gleason sums and serum PSA. In these men, age at diagnosis, serum PSA and clinical stage are the most significant predictors of requiring or selecting secondary treatment.     

The 20-Yr outcome in patients with well- or moderately differentiated clinically localized prostate cancer diagnosed in the pre-PSA era: the prognostic value of tumour ploidy and comorbidity

OBJECTIVE: This observational cohort study describes the long-term outcome of patients with clinically localized prostate cancer managed with watchful waiting, the prognostic value of tumour ploidy, and the impact of comorbidity. METHODS: A total of 119 patients with clinically localized (T1-2) prostate cancer consecutively diagnosed from 1978 to 1982 were prospectively managed by watchful waiting, with treatment given if progression occurred. RESULTS: Median age was 68 yr. Median observation time was 24 yr+/-6.25 (SD). Of the 112 patients who died, 42 died of prostate cancer. Disease-specific survival rates were 85% (95% CI: 77-93%), 58% (46-70%), and 32% (19-46%) at 10, 15, and 20 yr, respectively. Treatment-free survival rate was 43% (95% CI: 33-54%) at 10 yr. Patients aged 70 yr and over had a statistically significant increased risk of dying from any cause. There was a statistically significant increased risk of dying from prostate cancer for patients with nondiploid tumours. CONCLUSION: In the present series from the pre-PSA era, watchful waiting yielded a relatively high long-term disease-specific survival rate in patients with well- or moderately differentiated clinically localized prostate cancer, and almost half were not treated 10 yr after diagnosis. Watchful waiting may be an option at least for such patients with a 10- to 15-yr life expectancy. Age of 70 yr or more predicted an increased overall mortality. High comorbidity increased the risk (although not statistically significant) for death from any cause and for death from prostate cancer. Patients with nondiploid tumours were at an increased risk to die from prostate cancer.     

Clinical characteristics of prostate cancer in Gunma Prefecture

Prostate cancer clinical data from patients registered at Gunma University Urologic Oncology Study Group were compared between pre-PSA and PSA eras, dividing them between those patients diagnosed at clinical practice and those diagnosed on the Gunma mass-screening programme.
In the MS, the number of incidents of prostate cancer increased from 126 out of 16750 screened cases in the pre-PSA era (0.75%) to 227 out of 19782 screened cases in the PSA era (1.15%). The average age was lower in the PSA era. As for clinical stage, stage B and C cases increased while stage D cases decreased.
For the clinical practice cases at the Gunma University Urologic Oncology Study Group, the number of registered incidents of prostate cancer increased from 1164 in the pre-PSA era to 2098 in the PSA era. The average age was similar between the pre-PSA and PSA eras. The percentage of cases who were stage D declined from 46.1 during the pre-PSA era to 37.7 in the PSA era.
In the PSA era, earlier and more cases of prostate cancer are diagnosed both in clinical practice and in the mass screening program in Gunma Prefecture.     

Probability of finding T1a and T1b (incidental) prostate cancer during TURP has decreased in the PSA era

The purpose of this study is to assess the likelihood of detecting stage T1a and T1b cancer in transurethral prostatectomy specimens during the PSA era. Comparison was made of transurethral resection of prostate (TURP) cohorts in the pre-PSA era (1986-1987) and the PSA era (1994-2000), excluding patients with known PCa. A total of 228 men without a known history of prostate cancer underwent TURP during the pre-PSA era time frame and 501 underwent the procedure during the PSA era time frame. Malignancy diagnosed at the time of TURP decreased from 14.9 to 5.2% of patients in the pre-PSA and PSA eras, respectively. Stage T1a decreased from 4.4 to 2.4% and Stage T1b decreased from 10.5 to 2.8% of patients in the pre-PSA and PSA eras, respectively (P<0.001, Fisher's exact test). Prostate cancer newly identified during TURP has decreased significantly in the era of PSA screening in our study population, with the most significant drop being in clinically significant stage T1b. The decrease in TURP rates reduces the overall incidence of T1a/b cancer but cannot explain the lower risk of detecting previously unsuspected cancer at the time of any given TURP. Identification of many men with occult prostate cancer before TURP through screening and early detection is the most likely cause of this finding. These data suggest that men considering surgical or medical management of benign prostatic hyperplasia may be informed that it should be infrequent that men properly evaluated for prostate cancer will harbor clinically significant undetected malignancy.     

Clinical characteristics of prostate cancer in Japanese men in the eras before and after serum prostate-specific antigen testing

BACKGROUND: We retrospectively reviewed a large series of Japanese men with histologically proven prostate cancer to assess the clinical characteristics of the cancer in three different eras of prostate cancer management since prostate-specific antigen (PSA) testing started in 1988. METHODS: The medical records of 1125 patients treated between 1975 and 2002 were reviewed with respect to age, chief complaints, clinical stage, tumor grade, treatment options at each stage, and prognosis. We classified the patients as follows: those treated in the pre-PSA era between 1975 and 1988 (n=182), those treated in the PSA era between 1988 and 1997 (n=301; PSA era phase 1) and the PSA era between 1998 and 2002 (n=642; PSA era phase 2). RESULTS: Compared with the pre-PSA era, there were significant increases in the proportion of well-differentiated adenocarcinoma with respect to the biopsy tumor grade (24 vs 35%, P<0.01), in the proportion of linically organ-confined disease (21 vs 43%, P<0.001), and in the proportion of patients who underwent radical prostatectomy (13%vs 20%, P<0.01) after PSA testing was introduced. In addition, there was a significant difference in the proportion of subjects who were 70--79 years of age between the pre-PSA era (52%, 95/182) and the PSA era phase 2 (42%, 270/642, P<0.05). There was also a significant difference in the proportion of patients who underwent surgical castration between the pre-PSA era (78%) and PSA era phase 2 (10%, P<0.001). The proportion of patients participating in prostate cancer screening increased from 3% (pre-PSA era) to 11% (PSA era phase 1 and PSA era phase 2, P<0.05). In all clinical stages, there were significant differences between the pre- and post-PSA eras in cause-specific survival rates (5-year: 74 vs 94% in stages A and B, P<0.01; 54 vs 89% in stage C, P<0.001; 32 vs 53% in stage D, P<0.001). CONCLUSIONS: Migrations in the age of patients (toward younger patients), the stage of the cancer (towards earlier stages) and the histological findings (toward favorable findings), in addition to changes in treatment options, have contributed to the prolonged survival of Japanese men with prostate cancer after the PSA testing was introduced.     

What is low-risk prostate cancer and what is its natural history?

This article reviews the definition, incidence, pathological characteristics and natural history of low risk localised prostate cancer. Low risk disease is typically defined as clinical stage T1/T2a, biopsy Gleason score ≤6, PSA < 10. This risk classification has provided a useful system for reporting of outcomes and for the production of clinical guidelines. However, the low-risk disease is a broad category with a range of pathological characteristics and clinical behaviour. Many, but not all, low-risk prostate cancers are clinically insignificant, destined never to cause any harm. The challenge of managing low risk localized prostate cancer is to distinguish patients with clinically relevant cancers, who may benefit from radical treatment, from the remainder who do not need any intervention. The natural history of untreated low-risk localised prostate cancer has not been well studied, partly because it is a relatively recent entity, and partly because it has been standard practice for men with low risk disease to receive treatment. Data from watchful waiting in the pre-PSA era, modelling studies to take account of the lead time and overdiagnosis associated with PSA testing, and the early results of active surveillance can all provide insights into the likely natural history of low risk disease. There remains a major unmet need for markers of individual prostate cancer behaviour within the low-risk category. Such markers could be used to distinguish those men with truly indolent disease, suitable for observation, from those with significant prostate cancer that stand to benefit from treatment.     

Delayed therapy with curative intent in a contemporary prostate cancer watchful-waiting cohort

OBJECTIVE: To identify predictors of delayed therapy with curative intent, an increasingly common option in contemporary patients with prostate cancer who initially choose watchful waiting. PATIENTS AND METHODS: The characteristics of all patients at one institution and diagnosed with T1-4NXM0 prostate cancer between 1993 and 2000 were prospectively recorded. Factors recorded included: age, tumour stage, histological type, Gleason score, serum prostate specific antigen (PSA) level, prostate volume, PSA density (PSAD), percentage of positive biopsy cores, and the initial treatment selection. Outcomes, including all cancer-directed interventions, all serum PSA values, and initial outcomes of all interventions with curative intent, were determined by review of all medical records and cancer registry data. RESULTS: Of 187 patients on watchful waiting, 175 had stage T1 or T2 cancer and were analysed primarily. Thirty-eight (22%) of these patients received delayed intervention with curative intent (15 radical prostatectomy, 17 external beam radiotherapy, six brachytherapy). Age (P < 0.001) and percentage of positive biopsy cores (P = 0.042) were significant independent predictors of intervention with curative intent. When the PSA doubling time was added to the model it became a significant predictor (P = 0.018), with percentage positive biopsy cores (P = 0.022) and age (P < 0.001). CONCLUSIONS: Therapy with curative intent is common in contemporary patients with prostate cancer who initially choose watchful waiting. Age and percentage positive biopsy cores are independent predictors of such intervention, with PSA doubling time also an independent predictor.     

Watchful waiting for prostate cancer: a review article

As earlier detection of prostate cancer increases because of prostate-specific antigen (PSA) testing, appropriate use for watchful waiting warrants re-evaluation. We have drawn together the significant watchful waiting literature and used it to evaluate the use of watchful waiting in the PSA era. We conducted literature searches for studies examining outcomes of watchful waiting and examined new literature emerging about the use of PSA for the follow-up of watchful waiting patients. Watchful waiting has the potential to play an increasingly important role in prostate cancer as less advanced disease is detected and methods are refined for identifying low-risk patients.     

Contemporary survival results and the role of radiation therapy in patients with node negative seminal vesicle invasion following radical prostatectomy

PURPOSE: Seminal vesicle invasion (SVI) in a radical prostatectomy (RRP) specimen is associated with a guarded prognosis. We evaluated patients with SVI treated in the pre-prostate specific antigen (PSA) (1983 to 1991) and PSA (1992 to 2003) eras. MATERIALS AND METHODS: Of patients with prostate cancer treated with RRP from January 1983 through March 2002, 220 with SVI were evaluated, including 67 in the pre-PSA era and 153 in the PSA era. Postoperative PSA greater than 0.2 ng/ml was considered biochemical evidence of cancer progression. Survival rates were compared using Kaplan-Meier estimates to calculate progression-free, cancer specific and all cause survival. Multivariate Cox proportional hazard models were used to correlate variables with disease progression. RESULTS: The incidence of SVI in the PSA era was lower than in the pre-PSA era (6.0% vs 10.2%, p = 0.001). To date 124 patients (56%) have had evidence of cancer progression. The 4 and 7-year progression-free, cancer specific and all cause survival rates were significantly higher in men with SVI in the PSA era (p = 0.02). PSA at diagnosis, cancerous surgical margins and higher Gleason score were significantly associated with progression. Neither adjuvant nor salvage radiotherapy appeared to confer a significant progression-free survival benefit. CONCLUSIONS: The incidence of SVI has decreased in the PSA era. Progression-free, cancer specific and all cause survival rates following RRP in patients with SVI have improved in the PSA era. This may reflect earlier detection in this pathological tumor stage and more favorable prognostic factors associated with PSA screening. Adjuvant radiotherapy does not appear to confer any therapeutic benefit. Salvage radiotherapy can lead to durable PSA regressions in a small percent of men, although no long-term survival advantage can be proved.     

Management and survival of screen-detected prostate cancer patients who might have been suitable for active surveillance

OBJECTIVE: Screening practices for prostate cancer have resulted in an increasing incidence of prostate cancers. Our knowledge about which prostate cancers are life threatening and which are not is limited. Thus, for ethical, medical, and economic reasons we need to define which patients can be managed by active surveillance. METHODS: From 1993 through 1999, men from the Rotterdam section of the European Randomized study of Screening for Prostate Cancer (ERSPC) were screened by two strict protocols, which were based on prostate-specific antigen (PSA), digital rectal examination, and transrectal ultrasound. For this study, men with criteria that reflect current active surveillance studies were selected: those with a biopsy Gleason score < or =3+3 in two or fewer cores, with a PSA density <0.2 and a maximum PSA-level of 15 ng/ml. Clinical stage had to be T1C or T2. RESULTS: Of the 1,014 prostate cancers detected in the prevalence screen, 293 men (28.9%) met the criteria for active surveillance. Their mean age was 65.7 and the mean PSA level was 4.8 ng/ml. Radical prostatectomy was elected by 136 men (46.4%), radiotherapy by 91 (31.1%), and watchful waiting by 64 (21.8%). The mean follow-up was 80.8 months. The eight-year prostate cancer-specific survival was 99.2%; the overall survival was 85.4%. Nineteen men who chose watchful waiting changed to definitive treatment during follow-up. CONCLUSION: Only three men died of prostate cancer, none of whom were on watchful waiting. Our observations provide preliminary validation of the arbitrary selection criteria for active surveillance.     

Patterns of treatment of patients with prostate cancer initially managed with surveillance: results from The CaPSURE database. Cancer of the Prostate Strategic Urological Research Endeavor

PURPOSE: We determined the demographic and clinical profile of men who elect surveillance as the initial management of prostate cancer as well as the incidence and predictors of secondary treatment of these patients. MATERIALS AND METHODS: The Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) is a national disease registry of patients with various stages and treatments of prostate cancer. Using this database of 4,458 men we identified 329 (8.2%) who elected surveillance as the initial management of prostate cancer. Patients choosing watchful waiting were compared to other CaPSURE participants using the chi-square test. The likelihood of treatment initiation in the watchful waiting group was calculated using the Kaplan-Meier method. After adjusting for patient age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage and total Gleason score the Cox proportional hazards regression model was used to determine significant predictors of treatment initiation. RESULTS: Compared with others in the database, patients on watchful waiting were more likely to be 75 years old or older (51% versus 16%, p <0.001), white (93% versus 85%, p <0.001), and have lower serum PSA (p <0.001), organ confined disease (97% versus 88%, p <0.001) and a total Gleason score of 7 or less (97% versus 88%, p <0.001). In the watchful waiting group there was a 52% likelihood of treatment initiation within 5 years of the diagnosis. Significant predictors of secondary treatment were age younger than 65 years and elevated serum PSA at diagnosis. Neither race, extraprostatic stage cT3 disease nor higher total Gleason score was a significant predictor of treatment. CONCLUSIONS: Men who elect initial watchful waiting for prostate cancer tend to be older, have lower serum PSA and more favorable disease characteristics than those who seek treatment. PSA at diagnosis is the dominant factor for predicting secondary treatment.     

Conservative management of prostate cancer in the prostate specific antigen era: the incidence and time course of subsequent therapy

PURPOSE: The long natural history of early stage prostate cancer is well recognized and a conservative approach to the treatment of elderly men is often encouraged. We assessed the ability of patients and physicians to adhere to a policy of watchful waiting in the prostate specific antigen (PSA) era. MATERIALS AND METHODS: We retrospectively reviewed the records of all 199 men with stages T1-2 prostate cancer and PSA less than 20 ng./ml. who in our practice elected watchful waiting. Median followup in the population overall was 3.4 years. We performed Kaplan-Meier actuarial analysis of overall and disease specific survival, and most pertinent survival free from therapy. A questionnaire was administered to record the attitude of patients who ultimately proceeded to treatment to determine how therapy was triggered. RESULTS: Median patient age was 71 years and median PSA was 6.6 ng./ml. The tumor was impalpable in 52% of patients, Gleason sum was 6 or less in 80% and 11% used some form of herbal remedy or nutritional supplementation. Of the 37 men who died during observation, including 35 of co-morbid illness, only 6 underwent treatment. Overall survival at 5 and 7 years was 77% and 63% but disease specific survival was 98% and 98%, respectively. A total of 64 patients underwent treatment and actuarial freedom from treatment was 56% at 5 years, including 51% and 73% in those younger and older than 75 years at diagnosis. The likelihood of being alive and free from treatment was 43% at 5 years and 26% at 7. Of the 63 men treated 48 (76%) underwent radical therapy (brachytherapy in 17, external beam radiotherapy in 29 and prostatectomy in 2), while only 24% received androgen deprivation. The median PSA increase from diagnosis to treatment in treated patients was 2.9 ng./ml., and it was 0.9 ng./ml. from diagnosis to the last followup in those not treated. Of the treated patients 81% believed that the physician had initiated therapy due to a PSA increase or a nodule. However, physicians recorded having advocated treatment in only 24% of cases. CONCLUSIONS: When patients do not die of co-morbid illness, they are likely to proceed to therapy well within the first decade after diagnosis (57% by 5 years and 74% by 7). Therapy was usually definitive (radical) and triggered by slight, inevitable PSA increases. The patient perception was that the physicians initiated therapy in response to increasing PSA. However, the physicians more often perceived that treatment was initiated by patients. Therefore, watchful waiting in the PSA era often represents radical therapy delayed by a few years.     

EVALUATION OF CHANGES IN PROSTATE SPECIFIC ANTIGEN IN CLINICALLY LOCALIZED PROSTATE CANCER MANAGED WITHOUT INITIAL THERAPY

Purpose

We define changes in prostate specific antigen (PSA) measurements with time in 49 men 71.9 +/− 7.0 years old (mean plus or minus standard deviation) with clinically localized prostate cancer who remain untreated.

Materials and Methods

We retrospectively analyzed PSA changes in prostate cancer patients managed by watchful waiting. In all patients a minimum of 3 PSA levels were measured at intervals of at least 6 months after malignancy was diagnosed. The rate of change in serum PSA level with time (PSA velocity) was determined using an exponential, log linear model.

Results

In 49 patients treated conservatively mean initial PSA level plus or minus standard deviation was 12.3 +/− 11.1 ng./ml. and mean PSA followup during which no therapy for prostate cancer was introduced was 32.1 +/− 13.2 months. PSA levels decreased during the observation period in 11 of the 49 patients (22%) and median PSA doubling time in the remaining 38 was 55.7 months (range 15.1 to 994.5). There was no significant correlation between age at diagnosis, Gleason sum, initial PSA level or clinical stage and PSA velocity. The short-term rate of change in PSA during the first 9 months after prostate cancer was diagnosed correlated poorly with overall PSA velocity. The short-term rate of PSA change was greater than the overall rate of change in 14 of 37 patients (38%).

Conclusions

There is significant variability in the rate of change of PSA with time in men with clinically localized prostate cancer who remain untreated. The usefulness of serial PSA measurements in the management of watchful waiting is unclear. Changes in PSA may not be helpful or appropriate in determining the need for therapy after a period of observation.     

The face of high risk prostate cancer

OBJECTIVES: To define high risk prostate cancer using prostate cancer specific mortality as the key outcome metric. METHODS: Data from two population based cohorts of men from Connecticut who were diagnosed with localized prostate cancer were analyzed to determine the natural history of prostate cancer and the impact of treatment on long term survival. RESULTS: Men with Gleason 7-10 prostate cancer and a potential survival of 10 years have a high risk of dying from their disease if they elect active surveillance. Surgery appears to offer an improved survival for these men when compared to radiation therapy or observation. Men diagnosed with Gleason 6 tumors in the contemporary era are more likely to harbor low risk prostate cancer when compared to historical series. CONCLUSIONS: Our studies confirm that high risk prostate cancer is best identified by Gleason score 7-10, but challenge the concept that men with high-grade disease are less likely to benefit from radical surgery. Men who have rising PSA values following treatment with either surgery or radiation have residual prostate cancer and are at very high risk of dying from prostate cancer within 10 years.     

The role of volume-weighted mean nuclear volume in predicting tumour biology and clinical behaviour in patients with prostate cancer undergoing watchful waiting

OBJECTIVE: To investigate whether the volume-weighted mean nuclear volume (MNV, the only means by which unbiased estimates of three-dimensional variables can be obtained from a two-dimensional section by stereological methods) at diagnosis correlates with tumour biology and clinical behaviour in patients with prostate cancer treated by watchful waiting. PATIENTS AND METHODS: In a prognostic study, 64 patients with clinically localized prostate cancer were followed prospectively with initial expectant management. The median (mean, range) follow-up was 22 (27, 6.0-68) months. The prostate specific antigen (PSA) doubling time (PSADT) was calculated by linear regression. The MNV was estimated using biopsy specimens, based on a stereological method, and compared with PSADT and traditional clinicopathological variables. RESULTS: PSADT was significantly associated with MNV, but not with other clinicopathological variables. The PSA 'rapid-riser' subset (PSADTor=median value) and PSA-stable subsets (P = 0.0017 and 0.004, respectively). On multivariate analysis using a stepwise Cox proportional hazards regression, only MNV remained independently significant as a predictor of clinical progression among the clinicopathological variables (P < 0.001). CONCLUSIONS: These findings suggest that cancer cell nuclear volume is significantly associated with tumour biology and behaviour in patients with prostate cancer. Although further study with a larger patient population is needed to confirm the findings, estimates of MNV may be an important prognostic indicator in men treated with watchful waiting.     

Validity of prostate-specific antigen as a tumour marker in men with prostate cancer managed by watchful-waiting: correlation with findings at serial endorectal magnetic resonance imaging and spectroscopic imaging

OBJECTIVE: To investigate the validity of prostate-specific antigen (PSA) as a tumour marker in men with clinically localized prostate cancer who have selected watchful waiting, by determining if serial PSA level measurements are correlated with findings of malignancy or benign prostatic hyperplasia (BPH) at serial endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI). PATIENTS AND METHODS: We retrospectively identified 69 men with biopsy-proven prostate cancer being managed by watchful waiting, who underwent serial endorectal MRI/MRSI and who had contemporaneous serial PSA measurements. The mean (range) follow-up was 392 (294-571) days. A panel of three experienced readers reviewed the initial and follow-up MRI/MRSI studies, and classified findings of prostate cancer as stable or progressive. Another reader assessed BPH by calculating total gland and central gland volumes on all studies. RESULTS: At the follow-up MRI/MRSI, 51, 17 and one patient had stable, progressive, or unevaluable prostate cancer, respectively. The mean PSA velocity was significantly greater in patients with radiologically progressive disease (1.42 vs 0.42 ng/mL/year, P = 0.04). A PSA velocity of >0.75 ng/mL/year identified those with radiologically progressive disease with a true-positive fraction of 0.71 and a false-positive fraction of 0.39. PSA levels were not correlated with changes in total or central gland volumes (P > 0.05). CONCLUSIONS: In men with clinically localized prostate cancer who select watchful waiting, serial PSA levels are correlated with findings of malignancy but not BPH at serial endorectal MRI/MRSI, suggesting that PSA is a useful longitudinal tumour marker in this population.     

Clinical characteristics of prostate cancer in elderly Japanese patients 80 years of age or older

OBJECTIVE: Prostate adenocarcinoma is predominantly a disease of elderly men. This study retrospectively examined prostate adenocarcinoma in Japanese patients 80 years of age or older to determine the natural history and prognosis of this malignancy in the elderly population. METHODS: The medical records of 593 patients were reviewed, with respect to age, histologic grade, clinical and pathological stage, treatment modality and clinical outcome. A variety of possible clinical factors were compared between patient groups > or = 80 and < 80 years old. RESULTS: No significant difference in clinical stage, tumor grade, and performance status (PS) was found between two age groups of patients with prostate cancer. A significant stage migration between pre-PSA era and PSA era was found only in the group < 80 years old. In the series of stage D2 cancer patients, while there was no significant difference in cause-specific and progression-free survival rates between the two groups, the younger group < 80 years old had a better marker response at 3 months from the start of endocrine therapy compared with the older group (P = 0.0048, chi2 analysis). CONCLUSION: These data suggest that patients > or = 80 years with prostate cancer present with similar histologic grade and disease stage as younger patients, although the younger group with stage D2 had a better marker response to endocrine therapy.     

Watchful waiting versus active surveillance: Appropriate patient selection

The prostate-specific antigen (PSA) screening era has seen dramatic stage and age migration in patients with newly diagnosed prostate cancer. The average serum PSA level of newly diagnosed patients is about 6 ng/dL, and 60% of patients are diagnosed with clinical stage T1c disease. There is evidence that many low-grade and low-stage prostate cancers have a slow growth rate and protracted clinical course, with a very low threat of metastasis or death over a prolonged interval. Many men are also appropriately concerned about the impact of prostate cancer treatment on sexual and urinary function. Therefore, delaying therapy in favor of careful surveillance, with the expectation of delivering curative treatment upon evidence of progression, is an attractive concept. In this review, we discuss active surveillance, contrast it to watchful waiting, and define common inclusion criteria. We compare follow-up regimens and discuss indications and intervention outcomes after active surveillance. Finally, we support well-designed prospective clinical trials that evaluate active surveillance compared with immediate definitive treatment.     

Evolving Indications for Active Surveillance in Low-Risk Localized Prostate Cancer

As a result of improvements in techniques for detecting prostate cancer, such as prostate-specific antigen (PSA) screening, prostate cancer is more frequently being detected while still localized within the prostate. Furthermore, the development of predictive nomograms has made it possible to estimate the risk (low, intermediate, or high) of disease progression for these patients. For some patients with low-risk, localized cancer, use of radical therapies may be inappropriate, exposing the patient unnecessarily to the traumas of surgery/radiotherapy and the concomitant complications associated with these treatment options. The protracted natural history often seen with low-risk, localized prostate cancers suggests that many of these patients may be suitable for less aggressive treatment options such as watchful waiting. Where this option is employed, a rigorous surveillance protocol is required to identify patients rapidly who are not performing well with such conservative management, and to facilitate prompt initiation of more aggressive treatment. For some patients with higher risk, non-metastatic disease, immediate hormone treatment with bicalutamide (‘Casodex’¹) 150 mg, which at 3 years’ median follow-up significantly improves progression-free survival compared with watchful waiting alone, could be considered as a treatment option.     

Counseling men with prostate cancer: a nomogram for predicting the presence of small, moderately differentiated, confined tumors

PURPOSE: Men diagnosed with clinically localized prostate cancer have a number of treatment options available, including watchful waiting, radical prostatectomy and radiation therapy. With the widespread use of serum prostate specific antigen (PSA) testing, prostate cancers are being diagnosed earlier in their natural history, with many tumors being small and of little health risk to the patient, at least in the short term. To better counsel men diagnosed with prostate cancer, we developed a statistical model that accurately predicts the presence of small moderately differentiated, confined cancer based on clinical variables (serum PSA, clinical stage, prostate biopsy Gleason grade and ultrasound volume) and variables derived from the analysis of systematic biopsies. MATERIALS AND METHODS: The analysis included 409 patients diagnosed by systematic needle biopsy with clinical stages T1c or T2a N0 or NX and M0 or MX prostate cancer who were treated solely with radical prostatectomy at 1 of 2 institutions. Additional biopsy features included number and percentage of biopsy cores involved with cancer and high grade cancer, in addition to total length of biopsy cores involved. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume and without poorly differentiated elements. Logistic regression was used to construct several prediction models and the resulting nomograms. RESULTS: Overall 80 (20%) of the patients had indolent cancer. The nomogram predicted the presence of an indolent cancer with discrimination (area under the receiver operating characteristics curves) for various models ranging from 0.64 to 0.79. Calibration of the models appeared good. CONCLUSIONS: Nomograms incorporating pretreatment variables (clinical stage, Gleason grade, PSA and the amount of cancer in a systematic biopsy specimen) can predict the probability that a man with prostate cancer has an indolent tumor. These nomograms have good discriminatory ability and calibration, and may benefit the patient and clinician when the various treatment options for prostate cancer are being considered.