Richard Choo

OBJECTIVE: To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low‐to‐intermediate grade prostate carcinoma. PATIENTS AND METHODS: A prospective single‐arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful‐observation protocol with selective delayed intervention for clinically localized, low‐to‐intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. RESULTS: As of March 2003, 231 patients had at least 6 months of follow‐up (median 45) and at least three PSA measurements (median 8, range 3–21). The distribution of the doubling time was: 50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. CONCLUSIONS: The doubling time of untreated clinically localized, low‐to‐intermediate grade prostate cancer varies widely.

To evaluate the practice patterns of Canadian urologists in the management of stage I testicular seminoma. A survey was conducted with a three-page questionnaire among Canadian urologists between July and November 2002. The overall response rate was 48%. The total number of completed and partially completed questionnaires was 198 and 212, respectively. Ninety-four responders described their practice as university-affiliated teaching centre, while 118 reported community-based or private practice. All ordered CT abdomen/pelvis with either chest x-ray or CT scan of chest for staging investigation. Only 1% would order a lymphangiogram. About one third would not offer surveillance as a management option for stage I testicular seminoma. When asked to rank, in order of preference, three management options (surveillance, adjuvant radiotherapy, and adjuvant chemotherapy) under four different clinical scenarios varying in perceived relapse risk and the presence/absence of fertility preservation concern, the majority selected adjuvant radiotherapy as the treatment of choice for a patient with high relapse risk or no fertility concern. When a patient had desire to preserve fertility as well as low relapse risk, surveillance was chosen as the preferred management strategy. There was no significant response difference between academic and community urologists. There was some variation among Canadian urologists in the management of stage I testicular seminoma. The issue of fertility preservation and perceived relapse risk were important factors influencing management decisions. There was no significant difference between academic and community-based urologists with respect to patient volume and management approaches.

OBJECTIVE: To assess the predictive value of serial bone scans as a surveillance tool for bone metastasis in men with clinically localized prostate cancer and managed with watchful observation. PATIENTS AND METHODS: A prospective single‐arm study was conducted to assess the feasibility of a watchful observation protocol with selective delayed intervention for patients with clinically localized prostate cancer, i.e. T1b‐T2bN0M0, a Gleason score of ≤ 7 and a prostate‐specific antigen (PSA) level of ≤ 15 ng/mL. Patients were managed expectantly as long as they did not meet the empirically predefined criteria of clinical, histological or PSA progression. Bone scintigraphy was repeated every year for the first 2 years, then every 2 years thereafter if the patient remained on watchful observation. When the follow‐up PSA level was> 15 ng/mL the patient underwent bone scintigraphy every year. RESULTS: In all, 244 eligible patients were enrolled into the study. With a median follow‐up of 30 months, 449 bone scans were taken (150 at baseline and 299 in follow‐up evaluations); all 299 follow‐up scans were negative for bone metastasis. Hence, the true rate of positive follow‐up bone scans was estimated to be 0–1.0% (95% confidence). In all, 171 patients had at least one follow‐up bone scan; of these, the number (%) of patients who had 1, 2, 3, 4 and ≥ 5 follow‐up scans was 89 (52), 53 (31), 17 (10), eight (4.7) and four (2.3), respectively. The PSA levels (ng/mL) corresponding to all follow‐up bone scans were: 214 scans at PSA < 10, 61 at 10–14.9, 18 at 15–19.9 and six at ≥ 20 (range 20.2–24.9). The probability of a negative bone scan was estimated to be 88–100% (95% confidence interval) when a PSA threshold of 15 ng/mL was used. CONCLUSION: The probability of positive findings in serial bone scans in untreated, localized, low to intermediate grade prostate cancer was low when the follow‐up PSA level remained < 15 ng/mL. Avoiding bone scans in this group of patients would translate into a significant cost saving and reduction in their psychological and physical burden. As for those with a follow‐up PSA of> 15 ng/mL, the role of serial bone scintigraphy remains undefined, as a longer follow‐up and a larger sample are needed.

Objective To quantify the effect of radiotherapy (RT) on urodynamic function 3 months after RT in patients with prostate cancer undergoing definitive external beam RT. Patients and methods Seventeen patients with clinically localized prostate cancer were accrued into a single‐arm prospective study. Sixteen of the patients completed a scheduled multichannel video‐urodynamic study at baseline and again 3 months after RT; the urodynamic variables were then compared to assess the nature and extent of urodynamic change caused by RT. Correlations were assessed between these quantitative changes and those in self‐assessed qualitative urinary function measured by International Prostate Symptom Score (IPSS), Quality of Life assessment index (QoL) and urinary functional enquiry. Results There were significant changes detected by the urodynamic study 3 months after RT in bladder volume at capacity (mean decrease 70 mL) and bladder volume at first sensation when supine (mean decrease 85 mL), and a lower postvoid residual volume (mean 50 mL). There was no significant change in the remaining urodynamic variables (including maximum flow rate and voided volume), nor in bladder compliance, bladder instability or bladder outlet obstruction. The self‐assessed qualitative urological function measured by the IPSS, QoL and median urinary frequency/24 h showed no significant change after RT. Conclusions This is the first quantitative study to prospectively evaluate the effect of RT on urodynamics in patients with prostate cancer. Only a few urodynamic variables changed significantly 3 months after RT, while most, including self‐assessed qualitative urinary function, did not. This finding corresponds well with the notion that most patients tolerate RT well and that acute RT‐induced urinary symptoms resolve successfully, with the return of lower urinary tract function to baseline levels by 3 months after RT.

The optimal management of clinically localized prostate cancer remains unresolved. Management options range from a conservative approach to definitive treatment. While evidence suggests that expectant management yields similar 10-year survival rates and quality-adjusted life years compared to definitive treatment, this approach alone will deprive some patients with potentially curable disease of the opportunity for curative therapy. Effective management of localized prostate cancer requires differentiation between patients with biologically aggressive disease, in whom curative therapy is strongly warranted, and those with indolent malignancy, in whom conservative management would be equally efficacious. A comparison of surveillance studies in the literature yields a striking similarity: every series contains a substantial subset of long-term survivors, particularly in patients with favorable clinical parameters. We describe a prospective clinical study to evaluate a novel approach in which the decision between definitive therapy and conservative management is determined by the rate of prostate-specific antigen (PSA) increase or the development of early, rapid clinical and/or histologic progression. We enrolled 250 patients followed with active surveillance with selective delayed intervention. Patients were followed with active surveillance until they met criteria defining significant PSA, clinical, or histologic progression. At a median follow-up of 42 months, 60 patients came off observation, while 140 have remained on observation. We conclude that an approach of active surveillance with selective intervention for patients with rapid biochemical or clinical progression is feasible, and that PSA doubling time appears useful in guiding intervention in patients managed initially with expectant management. A policy of close monitoring with selective intervention for the 15% who progress rapidly is appealing, and is currently being investigated in several clinical trials.

Objective To examine the change in the free/total prostate specific antigen ratio (f/tPSA) with time and to assess the potential value of serial measurements of f/tPSA as a determinant of disease progression in untreated, low‐to‐intermediate grade prostate cancer (T1b‐T2b N0M0, Gleason score 7 and PSA 15 ng/mL). Patients and methods In a prospective single‐arm cohort study from November 1995, patients were conservatively managed with watchful observation alone unless they met arbitrarily defined criteria (clinical, histological and biochemical) of disease progression. Patients were followed regularly and underwent blood tests including PSA and f/tPSA. The initial and mean f/tPSA and the rate of change of f/tPSA with time were evaluated against the rate constant for the PSA doubling time (PSATd). Correlation analyses were used to evaluate any association between baseline clinical variables and either the rate of change of f/tPSA or initial f/tPSA. Results As of December 2000, 161 of a total of 206 accrued patients had three or more f/tPSA measurements and formed the basis of the study (median age 70 years; median follow‐up 2.7 years). The median initial f/tPSA was 0.16; there was a significant negative correlation between this value and the initial total PSA. The mean f/tPSA and rate of change of f/tPSA with time were significantly negatively correlated with the rate constant for PSATd. Also, the rate of change of f/tPSA correlated negatively with clinical T stage, but not with other baseline variables, including initial PSA, age and Gleason score. Conclusion The f/tPSA in men with untreated, clinically localized prostate cancer varied widely. The negative correlation between the rate of change of f/tPSA with time and rate constant for PSATd suggests that both might provide valuable information to allow clinicians to develop a strategy for optimizing the timing of therapeutic intervention for those patients choosing watchful observation alone.

We assessed the feasibility of a watchful waiting protocol with selective delayed intervention using clinical, prostate specific antigen (PSA) or histological progression as treatment indications for clinically localized prostate cancer. In this prospective, single arm cohort study patients with favorable clinical parameters (stage T1b to T2b N0M0, Gleason score 7 or less and PSA 15 ng./ml. or less) are conservatively treated with watchful waiting. When a patient meets disease progression criteria, arbitrarily defined by the 3 parameters of the rate of PSA increase, clinical progression or histological upgrade on repeat prostate biopsy, appropriate treatment is implemented. Patients are followed every 3 months for the first 2 years and every 6 months thereafter. Serum PSA measurement and digital rectal examination are done at each visit and repeat prostate biopsy is performed 18 months after study enrollment. Since November 1995, the study has accrued 206 patients with a median followup of 29 months (range 2 to 66). Of these men 137 remain on the surveillance protocol with no disease progression, while 69 were withdrawn from study for various reasons. There was clinical, PSA and histological progression in 16, 15 and 5 cases, respectively. The estimated actuarial probability of remaining on the surveillance protocol was 67% at 2 years and 48% at 4. The probability of remaining progression-free was 81% and 67% at 2 and 4 years, respectively. A policy of watchful waiting with selectively delayed intervention based on predefined criteria of disease progression is feasible. This strategy offers the benefit of an individualized approach based on the demonstrated risk of clinical or biochemical progression with time and, thus, it may decrease the burden of therapy in patients with indolent disease, while providing definitive therapy for those with biologically active disease.

To evaluate practice patterns of the management of stage I seminoma of testis in Canada and a selected group in the United States. Survey among radiation oncologists treating genitourinary (GU) tumors in Canada and the RTOG GU committee members in the United States between January and March 2001. Response rate was 78% (73/93) in Canada and 67% (24/36) in the United States. Eighty-four percent described their clinical practice as a university affiliated teaching center, and 16% as community-based or private practice. Sixty-two percent, 31% and 7% would manage 1-5, 6-10 and > oe = 11 cases per year respectively. Almost all would perform chest x-ray (99%) and CT scan of abdomen and pelvis (100%) as staging investigation following radical inguinal orchiectomy. Forty percent also arranged CT scan of chest, while only 18% routinely obtained lymphangiogram. Seventy-eight percent offered surveillance as a management option and estimated that 20% (median) of patients would choose surveillance in their practice. Among four management options: (1. surveillance, 2. radiotherapy (RT) to the para-aortic region, 3. RT to the para-aortic and ipsilateral pelvis ('dog-leg'), 4. single-agent chemotherapy), the order of first preference was option 1 (44%), 2 (42%), and 3 (14%) for patients who wish to preserve fertility. When fertility was not a major concern, it was option 2 (43%), 3 (39%), and 1 (17%). The commonest dose-fractionation schedule was 25 Gy/20 fractions (68%). Others included 25 Gy/15 f (15%), and 25.5 Gy/17 f (4%). Forty-five percent chose the para-aortic region, while 53% used the 'dog-leg' as RT volume. Twenty-nine percent reduced RT volume from the 'dog-leg' to the para-aortic region as the result of MRC Phase III study published in 1999. There are significant variations in the practice pattern of the management of stage I seminoma of testis among radiation oncologists in Canada and a selected group in the United States.