High-intensity focused ultrasound as salvage therapy for patients with recurrent prostate cancer after external beam radiation, brachytherapy or proton therapy

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Salvage HIFU is a promising treatment option for local recurrence after radiation therapy, with morbidity comparable with other forms of salvage treatment. This study showed a long‐term follow up of salvage HIFU in men with recurrence of localized prostate cancer following not only external beam radiation therapy but also brachytherapy or proton therapy.

OBJECTIVE

To investigate the use of high‐intensity focused ultrasound (HIFU) as a salvage therapy in patients with recurrence of localized prostate cancer after external beam radiation (EBRT), brachytherapy, or proton therapy.

PATIENTS AND METHODS

We retrospectively reviewed the charts of all patients who had undergone salvage HIFU for biopsy‐proven prostate cancer after primary radiation therapy. Patient characteristics and oncological outcomes were assessed.

RESULTS

Records of 22 patients with a median (range) follow‐up of 24 (5–80) months were reviewed. Patients were men with presumed organ‐confined disease who had been treated with salvage HIFU following recurrent disease after EBRT (fourteen patients), brachytherapy (five patients: four with high‐dose brachytherapy using In¹⁹²; and one with low‐dose brachytherapy using Au⁹⁸) or proton therapy (three patients). The median (range) age at salvage HIFU was 65 (52–80) years, with a median (range) prostate‐specific antigen (PSA) level before radiation therapy of 14.3 (5.7–118) ng/mL and a median (range) PSA level of 4.0 (1.2–30.1) ng/mL before HIFU. The median (range) period to HIFU after radiation therapy was 36 (4–96) months. The biochemical disease‐free survival (bDFS) rate in all patients at 5 years was 52%. Rates of bDFS in low‐, intermediate‐ and high‐risk groups were 100%, 86%, and 14%, respectively. One of the twelve patients who received post‐HIFU prostate biopsy showed malignancy. Side effects included urethral stricture in four patients, grade I urinary incontinence in four patients, rectourethral fistula and epididymitis in one of each patient.

CONCLUSION

Salvage HIFU is a promising treatment option for local recurrence after radiation therapy, with morbidity comparable with other forms of salvage treatment.     

Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer

PURPOSE: To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy (EBRT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Between 2001 and 2003, 215 patients with locally advanced prostate cancer were enrolled in the study. Patients were registered as primary candidates of the study and were treated with 6 months of LHRH agonist, with short-term of antiandrogen treatment for flare-up prevention. Patients with PSA levels below 10 ng/ml after the 6-month endocrine treatment were randomly divided into two arms. Then, a total dose of 72 Gy was given to the prostate. After 14 months of the protocol treatment, patients were treated with continuous androgen ablation (arm 1) or intermittent androgen ablation (arm 2). RESULTS: A total of 188 cases (87%) remained in the protocol. The median PSA level at entry was 25.3 ng/ml. The Gleason score was 2-6 in 32 cases (16%), 7 in 94 cases (48%), and 8-10 in 68 cases (35%). The median PSA level showed a remarkable decrease to 1.1, 0.2, and 0.1 ng/ml, after 6, 8, and 14 months of the protocol treatment, respectively. Of the 157 cases treated with EBRT, 153 cases (97.5%) had no biochemical failure in the mean follow-up of 17.3 months. CONCLUSIONS: The present study may reveal the possibilities of intermittent endocrine therapy after EBRT. However, the follow-up interval is short and little can be said about the results observed so far, exception of acute tolerance and patient acceptance of the protocol.     

Pretreatment prostate specific antigen (PSA) and 2-year PSA dynamics: Early predictors of prostate cancer prognosis with external radiation therapy

IntroductionThe dynamics of prostate specific antigen (PSA) in patients who have prostate cancer and receive radiotherapy is a very interesting but complicated topic. We tried to plot the sequential changes of PSA with and without hormone therapy and tried to find out the predictors for the high-risk patients for prostate cancer recurrence.MethodsWe reviewed the medical records of 164 prostate cancer patients who underwent intensity-modulated radiation therapy (IMRT) as the primary treatment. We recorded the patients' age, initial PSA, cancer grading at diagnostic biopsies (Gleason's score), clinical stage, the IMRT dosage, neoadjuvant, concomitant, and prolonged hormone therapy, follow-up PSA levels, biochemical progression, and distant metastasis.ResultsOf the 84 patients undergoing radiotherapy for prostate cancer with complete data for analysis, the biochemical failure-free survival (BFFS) rate was 88.09%. The patients with an initial PSA of less than 10 ng/mL had the best BFFS. Of the patients receiving neoadjuvant hormone therapy (NHT), serum PSA levels were significantly higher in those with biochemical failure than those without biochemical failure in the 3 months after radiation therapy. As for the patients free of biochemical failure, the mean PSA fell below 1 ng/mL immediately after IMRT for the NHT(+) group and at 9 months after IMRT for the NHT(–) group.ConclusionFor the patients with localized prostate cancer who underwent IMRT, initial PSA could predict clinical stage, 1-year BFFS, and 2-year BFFS. The follow-up PSA, as early as 3 months, was of clinical predictive value.     

External beam radiation monotherapy for prostate cancer

BACKGROUND: To clarify the implications and limitations of external beam radiation monotherapy for localized prostate cancer, the long-term outcomes and prognostic factors were investigated. METHODS: Between 1976 and 1994, 91 patients with untreated prostate cancer were treated with external beam radiation therapy alone. Thirty-two were classified as T1b, eight were T2a, four were T2b and 47 were T3. Pelvic lymphadenectomy was carried out in 69 cases; 57 were staged as pN0, eight were pN1, four were pN2 and 22 were pNX. Linac X-rays were used in 55 cases, fast neutron in 15 and a combination of the two in 21. No other therapy was given until relapse and when relapse was evident endocrine therapy was started. RESULTS: The observation period ranged from 3 to 206 months with a median of 78 months. Local control rate and disease-free, cause-specific and overall survivals at 10 years were 74.0, 49.6, 74.2 and 39.2%, respectively. By univariate analysis, T category, pN category and histologic grade were significant prognostic indicators for disease-free survival. Multivariate analysis revealed that T category was an independent prognostic factor. In T2b and T3 diseases, pN0/1 patients demonstrated significantly better disease-free survival than pNX. CONCLUSIONS: A favorable long-term outcome was achieved by external beam radiation monotherapy in patients with minimally extended prostate cancer (T1b and T2a). For locally advanced disease (T2b and T3), staging pelvic lymphadenectomy would be useful for the selection of patients.     

High-dose rate iridium-192 brachytherapy and external beam radiation therapy for prostate cancer with or without androgen ablation

Aim: To report the results of our feasibility study incorporating iridium‐192 high‐dose‐rate (HDR) afterloading brachytherapy and external beam radiation therapy (EBRT) for the treatment of prostate carcinoma and to assess the role of androgen ablation in conjunction with this treatment option. Methods: From July 2000 to June 2002, 42 patients with clinically localized or locally extensive prostate carcinoma were treated with HDR iridium‐192 brachytherapy and EBRT with or without androgen ablation. The median follow up was 16.5 months. Results: The technique of HDR brachytherapy and EBRT proved to be feasible with acceptable morbidities. Continuous prostate‐specific antigen (PSA) reduction was noted in all patients and no PSA failure was noted during follow up. Within 1 year, the decline of PSA nadir values less than 1 ng/mL was faster in patients with the addition of androgen blockade (P = 0.001). However, within 1 year, PSA nadir values less than 1.0 ng/mL can be achieved in all patients whose initial PSA is less than 20 ng/mL, with or without hormone blockade. Conclusions: The need for hormonal therapy in favorable‐risk brachytherapy patients (PSA < 20 ng/mL) might be less than the need for intermediate‐ or high‐risk patients. The use of hormonal therapy in intermediate‐risk patients (PSA ≥ 20 ng/mL) treated with HDR brachytherapy and pelvic EBRT is appealing, considering the favorable results. High dose rate brachytherapy appears to be an effective treatment for clinically localized and locally extensive prostate cancer, with minimal morbidity.     

Salvage radical prostatectomy for recurrent prostate cancer after radiation therapy

Salvage radical prostatectomy is considered for patients with locally recurrent prostate cancer after external beam radiotherapy. Between 2001 and 2004, 32 men treated with curative intent with radiotherapy for prostate cancer were subsequently treated with salvage surgery for clinically localized prostate cancer. We assessed the morbidity associated with this procedure and the outcome of the patients. Thirty-two patients underwent salvage radical prostatectomy. Initial pre-radiation median prostate-specific antigen was 13 ng/ml. Pre-radiation disease was clinical stage T1b in five cases, T2a in 10, T2b in 10 and T3a in seven. Mean operative time was 122 minutes, intraoperative blood loss was 550 ml and hospital stay and catheterization time were 5 and 12 days, respectively. There was biochemical failure in eight patients after salvage radical prostatectomy and 24 patients are biochemical non evidence of disease (bNED). In recurrent prostate local disease with prostate-specific antigen <10 ng/ml and life expectancy greater than 10 years, salvage radical prostatectomy is a reasonable treatment option.     

Treatment decision-making in localized prostate cancer: why patients chose either radical prostatectomy or external beam radiation therapy

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Our patients’ personal preferences are of major importance for decision‐making in localized prostate cancer. The study evaluates strategies in choosing either RP or EBRT. Typical modes of reasoning consist of personal beliefs in patients choosing RP and fear of treatment related side‐effects in the EBRT group.

OBJECTIVES

? To evaluate patients’ treatment decision‐making for localized prostate cancer. ? To determine their willingness to participate in a randomized controlled trial (RCT) comparing radical prostatectomy (RP) with external beam radiation therapy (EBRT).

PATIENTS AND METHODS

? We investigated 31 patients with localized prostate cancer who had opted for either RP (n= 18) or EBRT (n= 13) as primary therapy. ? A semi‐structured interview and a short questionnaire were completed a few days after the start of treatment, covering all aspects of treatment decision.

RESULTS

? Most patients wanted to decide on their treatment together with their physician and were generally satisfied with the information provided. Internet resources were used more frequently by the RP group (14/18 patients) than by the EBRT group (three of 13 patients, P < 0.01). ? Physicians’ advice and other patients’ experiences were highly influential in the final treatment decisions. ? Patients deciding on RP were younger and their personal beliefs were their typical decision criteria (RP, six of 18 patients vs EBRT, none; P= 0.03). By contrast, possible treatment‐related side‐effects were a major concern for patients choosing EBRT (RP, two of 18, vs EBRT, seven of 14; P= 0.02). ? Only two patients (of 31, 6%) would have consented to random assignment to either RP or EBRT, while six (19%) patients were not averse.

CONCLUSIONS

? Patients are satisfied with the information provided and with their decision‐making process. ? Typical modes of reasoning can be found and mainly consist of personal beliefs in patients choosing RP and fear of treatment related side‐effects in those choosing EBRT. ? According to the sample, the participation rate for a RCT comparing RP to EBRT would not exceed 25% without further efforts.     

Carbon‐ion radiation therapy for prostate cancer

In 1994, carbon‐ion radiotherapy was started at the National Institute of Radiological Sciences using the Heavy‐Ion Medical Accelerator in Chiba. Between June 1995 and March 2000, two phase I/II dose escalation studies (protocols 9402 and 9703) of hypofractionated carbon‐ion radiotherapy for both early‐ and advance‐stage prostate cancer patients had been carried out to establish radiotherapy technique and to determine the optimal radiation dose. To validate the feasibility and efficacy of hypofractionated carbon‐ion radiotherapy, a phase II study (9904) was initiated in April 2000 using the shrinking field technique and the recommended dose fractionation (66 gray equivalents in 20 fractions over 5 weeks) obtained from the phase I/II studies, and was successfully completed in October 2003. The data from 175 patients in the phase II study showed the importance of an appropriate use of androgen deprivation therapy according to tumor risk group. Since November 2003, carbon‐ion radiotherapy for prostate cancer was approved as “Highly Advanced Medical Technology” from the Ministry of Health, Labor, and Welfare, and since then approximately 1100 patients have received carbon‐ion radiotherapy as of July 2011. In this review, we introduce our steps thorough three clinical trials carried out at National Institute of Radiological Sciences, and show the updated data of carbon‐ion radiotherapy obtained from approximately 1000 prostate cancer patients. In addition, our recent challenge and future direction will be also described.     

Gleason stratifications prognostic for survival in men receiving definitive external beam radiation therapy for localized prostate cancer

PurposeHistologic grade analyses for prostate cancer (PCa) have traditionally included Gleason scores (GS) of ≤6, 7, and 8-10. Stratified biochemical progression-free survival has increasingly been reported within these groups on analyses of primary-secondary patterns (PSPs) (e.g., 3+4 vs. 4+3) and overall GS (e.g., 8 vs. 9 vs. 10) but with limited data regarding stratified survival outcomes. In this analysis, outcomes for biopsy-assigned GS 6 to 10 were comprehensively evaluated to identify stratifications prognostic for survival in patients undergoing external beam radiation therapy (EBRT).MethodsThe Surveillance, Epidemiology, and End Results database was examined for T1–4 N0 M0, GS 6 to 10 PCa managed with EBRT alone from 2004 to 2006. GS and PSP variations were analyzed for PCa-specific survival (PCSS) and overall survival (OS).ResultsOverall, 26,885 patients were evaluated. Preliminary PSP analyses identified stratifications for 3+4 vs. 4+3 = 7 and 4+4 = 8 vs. GS 8 with pattern 5 (P5) (i.e., 3+5 and 5+3) as significant; however, no differences were observed for 4+5 vs. 5+4 = 9. The primary analysis included stratifications for GS 6, 3+4, 4+3, 4+4, 8 w/P5, 9, and 10, where the 7.5-year PCSS rates were 99%, 97%, 95%, 91%, 86%, 81%, and 78% and 7.5-year OS rates were 83%, 76%, 72%, 67%, 66%, 58%, and 54%, respectively. PCSS differences for sequential score increases were all significant on univariate analyses (all P<0.05). In sequential multivariate analyses of PCSS accounting for age, prostate-specific antigen, T stage, year, marital status, race, and tumor registry, the identified GS stratifications remained significant (all P<0.05), with the exception of GS 8 w/P5 vs. 9 (P = 0.11). In overall multivariate analyses, the identified GS stratifications represented the strongest prognostic factor for survival. Subgroup analyses demonstrated that presence of any P5 was an independent prognostic factor for survival.ConclusionIn the largest reported survival analysis of Gleason stratifications, biopsy-assigned GS 6, 3+4, 4+3, 4+4, 8 w/P5, 9, and 10 represented sequential prognostic factors for survival in patients managed with definitive EBRT.     

The value of external beam radiation in node positive prostate cancer: a multivariate analysis

Purpose: The goal of this study was to evaluate the effect of local/regional treatment, particularly external beam radiation alone vs. radical prostatectomy plus radiation therapy in patients with pathologic node positive prostate cancer on survival. Methods: Medical records of all 116 patients who received their initial treatment at the Massachusetts General Hospital between 1980 and 1996 for adenocarcinoma of the prostate with pathologic confirmed nodal metastases and no distant metastases were reviewed. The mean follow up was 5.5 years. Overall survival, time to PSA failure on endocrine therapy, and time to first intervention were evaluated. The effect of the different treatment options were compared using multivariate Cox proportional hazard models to adjust for tumor characteristics that might influence survival. These included clinical T stage, clinical N stage, Gleason grade, number and location of positive lymph nodes and pretreatment PSA. Results: The combined patient population had a 5-year survival rate of 74% and a 10-year survival rate of 48%. Patients receiving local/regional treatment had adjusted 5 year survival rates of 80% compared to 27% for patients receiving no local/regional treatment (p = .001) with corresponding cumulative intervention rates (CIR) of 11% vs. 73% (p = .01) Patients receiving external beam radiation (XRT) alone did not differ significantly from those receiving prostatectomy plus radiation therapy in terms of survival (75 vs. 82%, P = .23) or cumulative intervention rates (14% vs. 14%, P = .94) Conclusion: Although it appears that all patients with node positive prostate cancer will eventually develop failure, this paper suggests local/regional therapy offers a medium term survival advantage over no local/regional treatment. The addition of prostatectomy did not confer a demonstrable advantage over radiation alone.     

Adjuvant versus salvage radiation therapy for prostate cancer and the risk of death

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To investigate whether salvage radiation therapy (RT) for prostate‐specific antigen (PSA) failure can provide the same result as adjuvant RT, which decreases the risk of all‐cause mortality (ACM) for men with positive margins (R1), or extra‐capsular or seminal vesicle extension (pT3).

METHODS

We studied 1638 men at Duke University who underwent radical prostatectomy for unfavourable‐risk prostate cancer and whose postoperative PSA was undetectable. Cox regression was used to evaluate whether salvage vs adjuvant RT in men with a rapid (<10 months) or slow (≥10 months) PSA doubling time (DT) was associated with the risk of ACM, adjusting for adverse features (pT3, R1, Gleason score 8–10), age, preoperative PSA level, comorbidity and hormonal therapy use.

RESULTS

Despite fewer men with two or more adverse features (61 vs 82%; P = 0.016), salvage for a rapid PSA DT vs adjuvant RT increased the risk of ACM [adjusted hazard ratio (AHR) = 3.42; 95% confidence interval (CI) = 1.27–9.20; P = 0.015]. There was no difference (AHR = 1.39; 95% CI = 0.50–3.90; P = 0.53) in the risk of ACM among men who received salvage for a slow PSA DT or adjuvant RT. Nearly all (90%) men with a slow PSA DT had Gleason score ≤7 and the majority (59%) had at most pT3 or R1 disease.

CONCLUSION

Radiation therapy after PSA failure as compared with adjuvant RT was not associated with an increased risk of ACM in men with Gleason score ≤7 and pT3R0 or pT2R1 disease.     

Primary radiation therapy for localized prostate cancer

Prostate cancer in men is similar to breast cancer in women; both cancers rank first, respectively, in incidence and are normally responsive to radiation therapy. In addition, advances in mammography help detect earlier breast cancers, and the development and refinement of prostatic specific antigen (PSA) has resulted in early detection of low-stage localized prostate cancers. This has generated debate over the proper management of localized prostate cancer. While there have not been any controlled, prospective, randomized trials of sufficient power to compare the various local therapies, based on the current available data, the three commonly used local modalities, surgery, and external beam radiation therapy and brachytherapy (radioactive seed implant), have similar efficacy controlling the disease up to 10 years in many patients. Technological advances in treatment delivery and planning have improved the treatment of prostate cancer with external-beam radiotherapy using three-dimensional conformal radiotherapy (3DCRT), ultrasound-guided transperineal implant, or intensity-modulated radiotherapy (IMRT), as well as proton or neutron beam based therapies.     

Significance of prostatic biopsies after radiation therapy for carcinoma of the prostate

The significance of a prostatic biopsy after radiation therapy for prostatic cancer is at present uncertain. Criteria for interpreting residual tumor cells as viable and, more important, determining whether such cells are biologically capable of local growth and/or subsequent dissemination, by histological evaluation, require further clinical correlation and studies designed to better characterize biological behavior and growth potential of neoplastic cells in general and how this may or may not be altered by irradiation. A positive biopsy after radiation therapy must be regarded, however, as ominous simply because its potential significance is yet to be determined. Prostatic biopsies may predict treatment failure in general, but their significance relative to an individual patient requires correlation with 1) tumor stage, grade, size, and site of the original tumor; 2) technique of biopsy, number of cores obtained, and the location relative to the original tumor; 3) time interval of biopsy after treatment and whether biopsy is performed on one or more occasions; 4) circumstances (clinical progression or clinical regression) at the time of biopsy; and 5) treatment artifacts regarding dose delivered and distribution, which is especially important with regard to interstitial irradiation.     

Colorectal complications of external beam radiation versus brachytherapy for prostate cancer

BACKGROUND: Although radiation therapy plays a central role in the management of prostate cancer, complications remain a troubling byproduct. We sought to determine the prevalence and significance of colorectal complications after external beam radiation (EBRT) versus brachytherapy (BT) for prostate cancer. METHODS: We performed a retrospective review of all patients undergoing EBRT or BT for prostate cancer from January 1999 to October 2005. Toxicities were graded using the Radiation Therapy Oncology Group scoring system or the modified Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer grading criteria. RESULTS: A total of 183 patients underwent EBRT and 50 patients underwent BT with a mean follow-up period of 39 months. BT was associated with significantly less acute (6% vs 43.5%) and late toxicities (2% vs 21.8%; both P < .001). Among patients receiving EBRT, acute grade 3 toxicity was experienced by 1 (.5%) patient, and grade 2 toxicity was experienced by 79 (43%) patients. Increased stool frequency was the most common manifestation (62%), followed by rectal pain and urgency (30%) and rectal bleeding (21%). Late toxicity included 34 (18.6%) patients with grade 2 toxicity (bleeding, 68%; frequent stools, 26%; pain and urgency, 18%), and 5 patients (2.7%) with grade 3 toxicity (bleeding requiring multiple cauterizations, 3; small-bowel obstruction requiring surgery, 1; anal stenosis requiring repeat dilations, 1). BT was relatively well tolerated, with only 3 patients (6%) experiencing grade 2 acute toxicity symptoms of pain and urgency. One BT patient suffered late grade 2 toxicity of bleeding requiring intervention. One patient developed rectal cancer 20 years after EBRT. CONCLUSIONS: Despite its relative safety, radiation therapy for prostate cancer has a significant incidence of colorectal complications. Overall, BT has a significantly lower incidence of acute and late toxicities than EBRT.     

Androgen-deprivation therapy alone versus combined with radiation therapy or chemotherapy for nonlocalized prostate cancer: a systematic review and meta-analysis

In this paper, we reviewed the long-term survival outcomes, safety, and quality-of-life of androgen-deprivation therapy (ADT) alone versus combined with radiation therapy (RT) or chemotherapy for locally advanced and metastatic prostate cancer (PCa). A literature search was performed using OvidSP. Randomized controlled trials (RCTs) that met the following criteria were included: including locally advanced or metastatic PCa, comparing ADT alone versus combined with any treatment method and reporting quantitative data of disease control or survival outcomes. Finally, eight RCTs met the inclusion criteria. Among these, three compared ADT versus ADT plus RT (n = 2344) and one compared ADT versus ADT plus docetaxel–estramustine (n = 413) in locally advanced PCa; two compared ADT versus ADT plus docetaxel (n = 1175) and two compared ADT versus ADT plus estramustine (n = 114) in metastatic PCa. For locally advanced PCa, the addition of RT to long-term ADT can improve the outcomes of survival and tumor control with fully acceptable adverse effects. Specially, the pooled odds ratio (OR) of overall survival (OS) was 1.43 (95% confidence interval 1.20–1.71) when compared ADT plus RT with ADT alone (P < 0.0001). For metastatic hormonally sensitive PCa, the concurrent use of docetaxel plus ADT was effective and safe (pooled OR of OS: 1.29 [1.01–1.65]: P = 0.04). In all, long-term ADT plus RT and long-term ADT plus docetaxel should be considered as proper treatment option in locally advanced and metastatic hormonally sensitive PCa, respectively. The major limitation for the paper was that only eight RCTs were available.     

Clinical characteristics of bladder cancer in patients previously treated with radiation for prostate cancer

OBJECTIVE: To determine if bladder cancer diagnosed after prostatic radiation therapy (RT) differs in behaviour from bladder cancer diagnosed after prostate cancer not treated with RT, as such bladder cancer is thought to be more aggressive than de novo bladder cancer, and epidemiological studies show a higher rate of bladder cancer in patients after irradiation. PATIENTS AND METHODS: We reviewed our records to identify patients who had a diagnosis of bladder cancer with a previous diagnosis of prostate cancer. Patient age, date of diagnosis of prostate cancer, date of diagnosis of bladder cancer, symptoms, clinical stage, initial pathology, definitive therapy, definitive pathological stage, and disease status were recorded. RESULTS: In all, 100 patients were identified who had a diagnosis of bladder cancer after a diagnosis of prostate cancer between January 1992 and August 2003; 58 had had RT for prostate cancer. The mean time between a diagnosis of bladder cancer and prostate cancer was 62 months in the RT group and 34 months in the unirradiated group (P = 0.002) At diagnosis of bladder cancer, 56 (97%) of the patients who received RT had high-grade urothelial carcinoma, vs 27 (64%) of those not irradiated (P < 0.001). Thirty (52%) of the patients with RT had muscle-invasive bladder cancer, vs 17 (40%) of those not irradiated (P = 0.3). The survival rate was similar for both groups. CONCLUSIONS: Bladder cancer is diagnosed later, and is of higher grade, in patients who are irradiated for prostate cancer than in those treated with other methods. Patients with prostate cancer who are treated with RT should be monitored closely for the presence of bladder cancer.     

Matched-cohort analysis of patients with prostate cancer followed with observation or treated with three-dimensional conformal radiation therapy

OBJECTIVES: To compare the outcome of similar patients with prostate cancer treated by either observation or three-dimensional conformal radiation therapy (3-DCRT). PATIENTS AND METHODS: The study included 69 patients with nonmetastatic prostate cancer who were observed only; the indications included indolent disease, significant medical comorbidities and refusal of treatment. Of these, 62 patients had palpable T1-T2a and seven T2b-T3a disease, a median Gleason score of 6 and a median initial prostate-specific antigen (PSA) level of 5.3 ng/mL. A matched-cohort analysis of 69 patients, based on palpation T category, Gleason score and initial PSA, was used to compare the outcome between the observation and 3-DCRT groups. The median radiation dose for latter was 72 Gy. RESULTS: The median follow-up for the observed patients was 49 months. The 5- and 8-year actuarial rates of freedom from distant metastases were 100% and 93%, respectively, and the actuarial overall survival rates 94% and 73%, respectively. Seven observed patients had local disease progression on physical examination. Four patients who initially were observed received radiation therapy later for a rising PSA and/or local disease progression. For the 69 matched 3-DCRT patients, the overall 5-year rate for no biochemically evident disease was 74%. The respective 5- and 8-year actuarial rates of freedom from distant metastases were 95% and 95%, and actuarial overall survival rates 95% and 75%. There were no significant differences in distant metastasis and overall survival rates between the groups, and no deaths from prostate cancer in either group. CONCLUSIONS: Observation is a reasonable alternative to treatment in selected patients. During the 5-year follow-up the progression rates were relatively low, and there was no difference in distant metastasis or overall survival between the groups. As the follow-up was short a longer follow-up is needed to determine whether the outcome of those patients who chose observation will remain comparable to that in those undergoing immediate 3-DCRT.     

Health-related quality of life and psychosocial factors in patients with prostate cancer scheduled for radical prostatectomy or external radiation therapy

OBJECTIVE: To assess whether baseline health-related quality of life (HRQOL) and psychosocial profiles differ in patients with prostate cancer scheduled for radical prostatectomy (RP) or external radiation therapy (ERT), as there is evidence that HRQOL is influenced by psychosocial factors (PFs), so that any variation at baseline should be considered when comparing the effect of therapy on HRQOL. PATIENTS AND METHODS: Before receiving therapy, HRQOL and PFs were assessed in 65 patients scheduled for RP and in 73 scheduled for ERT. To measure HRQOL (generic and disease-specific) and PFs, an extended questionnaire was constructed, using validated and standardized instruments. Clinical data were collected from patients' medical records. Comparisons adjusted for age and socio-economic status (SES) were analysed using Student's t-test and univariate analyses of variance and covariance. RESULTS: Patients scheduled for ERT were 7.9 years older and had a lower SES (both P < 0.001), more often had stage T3 and T4 disease, had poorer histopathological differentiation and higher levels of prostate-specific antigen (all P < 0.01). They also reported a worse physical, role, cognitive and social function, more fatigue, more pain, a lower overall HRQOL and worse sexual function than patients scheduled for RP. There were no differences in urinary and bowel function, nor in the PFs assessed. CONCLUSION: The baseline HRQOL profile of patients scheduled for RP is better than in those scheduled for ERT. These results are in line with those from the few other studies on this subject. Knowing the impact of RP and ERT on HRQOL should therefore be based mainly on longitudinal studies including baseline measures, the analyses of which should be adjusted for age and SES. In the present small study, baseline PFs did not differ between the treatments.