Prostatic Neoplasms: Millar JL

Sidhom MA, Kneebone AB, Lehman M, Wiltshire KL, Millar JL, Mukherjee RK, Shakespeare TP, Tai KH. · Cancer Therapy Centre, Liverpool Hospital, NSW, Australia. · Radiother Oncol. · Pubmed #18514340 No free full text.

Abstract: BACKGROUND AND PURPOSE: Three randomised trials have demonstrated the benefit of adjuvant post-prostatectomy radiotherapy (PPRT) for high risk patients. Data also documents the effectiveness of salvage radiotherapy following a biochemical relapse post-prostatectomy. The Radiation Oncology Genito-Urinary Group recognised the need to develop consensus guidelines on to whom, when and how to deliver PPRT. MATERIALS AND METHODS: Draft guidelines were developed and refined at a consensus conference in June 2006 attended by 63 delegates where urological, radiotherapy and diagnostic imaging experts spoke on aspects of PPRT. Unresolved issues were further developed by working parties and redistributed until consensus was reached. RESULTS: Central to the recommendations is that patients with positive surgical margins, seminal vesicle invasion and/or extracapsular extension have a high risk of residual local disease and should be informed of the options of either immediate adjuvant radiotherapy or active surveillance with early salvage in the event of biochemical recurrence. Salvage radiotherapy should be instituted at the earliest confirmation of biochemical recurrence. Detailed contouring guidelines have been developed, defining the regions at risk of residual microscopic disease which should be included in the clinical target volume. The recommended doses are 60-64Gy for adjuvant, and 60-66Gy for salvage radiotherapy. The role of hormone therapy in conjunction with PPRT is yet to be defined. CONCLUSIONS: These consensus guidelines have been developed to give clinical and technical guidance to radiation oncologists and urologists in the management of high risk post-prostatectomy patients.

Newton FJ, Burney S, Millar JL, Frydenberg M, Ng KT. · School of Psychology, Psychiatry and Psychological Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia. · BJU Int. · Pubmed #16686708 No free full text.

Abstract: OBJECTIVES: To examine differences in sexual, urinary and bowel function, and bother, in patients with prostate cancer after treatment with radical prostatectomy (RP) or external beam radiation (EBRT), compared to a convenience sample of men with no diagnosis of prostate cancer, as little is known about the disease-specific health-related quality of life (HRQoL) of men in Australia after treatment for clinically localized prostate cancer. PATIENTS AND METHODS: The study was a retrospective cross-sectional survey of 95 controls, 82 men with localized prostate cancer treated with RP and 39 with EBRT at > or = 2 years before data were collected. Disease-specific HRQoL was assessed using the University of California Los Angeles Prostate Cancer Index, a validated measure that includes six subscales addressing sexual, urinary and bowel symptoms, and level of bother associated with the symptoms. Univariate analyses were conducted to ascertain differences in disease-specific HRQoL among the three groups. To minimize the influence of other factors, age and comorbid medical conditions were included as covariates. RESULTS: Men treated with RP had more sexual and urinary symptoms (both P < 0.001) than those treated with EBRT, and more sexual bother (P < 0.001). Men treated with EBRT reported significantly worse bowel function (P = 0.02) and more bother (P < 0.001) with these symptoms than those who had RP. CONCLUSIONS: Except for bowel dysfunction and the bother associated with these symptoms, disease-specific HRQoL was generally worse after RP than EBRT.

Millar JL, Longano AZ, Imbert SJ, Stokes D. · Melbourne Prostate Institute, William Buckland Radiotherapy Centre, The Alfred Hospital, Melbourne, Victoria, Australia. · Brachytherapy. · Pubmed #16563994 No free full text.

Abstract: PURPOSE: To describe a simple technique to define the anatomically accurate urethral location in the postimplant CT scans, after permanent prostate seed implants, without the discomfort associated with use of a catheter. METHODS AND MATERIALS: We perform preplanned, preloaded transperineal transrectal ultrasound-guided permanent seed implants for men with low-risk prostate cancer. In postimplant CT scans performed 4 weeks after the procedure we previously used a catheter to identify the urethra. We now use retrograde injection of contrast, followed by the retrograde injection of a mixture of contrast and aerated sterile lubricant jelly to opacify the urethra on our CT scans. RESULTS: This technique is economical, simple, and more comfortable than the use of a catheter. It reliably allows identification of the urethra for the purposes of deriving dose-volume histogram statistics, for quality control. It provides a reference for more accurate determination of the prostate apex. CONCLUSIONS: We recommend this technique to those performing prostate seed implants wishing to most accurately determine the precise urethral dose parameters in delayed postimplant CT scans, without the need for the discomfort associated with a urethral catheter.

Williams SG, Duchesne GM, Gogna NK, Millar JL, Pickles T, Pratt GR, Turner S. · Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. · Int J Radiat Oncol Biol Phys. · Pubmed #16530339 No free full text.

Abstract: PURPOSE: To evaluate the impact of an alternative biochemical failure (bF) definition on the performance of existing plus de novo prognostic models. METHODS AND MATERIALS: The outcomes data of 1,458 Australian and 703 Canadian men treated with external-beam radiation monotherapy between 1993 and 1997 were analyzed using a lowest prostate-specific antigen (PSA) level to date plus 2 ng/mL (L + 2) bF definition. Two existing prognostic models were scrutinized using discrimination (Somers Dxy [SDxy]) and calibration indices. Alternative prognostic models were also created using recursive partitioning analysis (RPA) and multivariate nomogram methods for comparison. RESULTS: Discrimination of bF was improved using the L + 2 definition compared with the American Society for Therapeutic Radiology and Oncology (ASTRO) definition using both the three-level risk model (SDxy 0.30 and 0.22, respectively) or the nomogram (SDxy 0.35 and 0.27, respectively). Both existing prognostic models showed only modest calibration accuracy. Using RPA, five distinct risk groups were identified based primarily on Gleason score (GS) and all subsequent divisions based on PSA. All GS 7-10 tumors were intermediate or high risk. This model and the developed nomogram showed improved discrimination over the existing models as well as accurate calibration against the Canadian data, apart from the 30-50% failure region. CONCLUSIONS: The L + 2 definition of bF provides improved capacity for discrimination of failure risk. New prognostic models based on this endpoint have overall statistical performance superior to those based on the ASTRO consensus definition but continue to have unreliable discrimination in the intermediate-risk region.

Williams SG, Duchesne GM, Millar JL, Pratt GR. · William Buckland Radiotherapy Centre and Monash University, Melbourne, Australia. · Int J Radiat Oncol Biol Phys. · Pubmed #15519778 No free full text.

Abstract: PURPOSE: To assess the impact of pretreatment prognostic factors plus subsequent biochemical failure on overall survival after radiotherapy for prostate cancer. METHODS AND MATERIALS: We analyzed the prostate-specific antigen (PSA) and survival records of 1571 men with clinically localized prostate cancer treated with external beam radiotherapy monotherapy at the former Queensland Radium Institute between 1990 and 1997. The pretreatment PSA level, biopsy Gleason score, clinical stage, patient age, and the development of biochemical failure were assessed in relationship to overall survival and cause-specific survival, using fixed, as well as time-dependent, statistics. RESULTS: The median follow-up was 88.1 months (95 months for those still alive). The actuarial overall survival, cause-specific survival, and biochemical failure-free survival rate at 10 years was 61.1%, 80.9%, and 25.9% respectively. Cause-specific survival was independently influenced by the pretreatment PSA level, Gleason score, clinical stage, and the development of biochemical failure (relative risk, 19.1). Using the overall survival endpoint, multivariate analysis showed age, pretreatment PSA level, Gleason score, and biochemical failure (relative risk 1.27) to be statistically significant variables. CONCLUSION: In addition to previously identified factors, the pretreatment PSA level and occurrence of biochemical failure after radiotherapy for prostate cancer are associated with an increased overall mortality risk. Both pretreatment PSA level and posttreatment biochemical failure are independent predictors of overall survival after radiotherapy for prostate cancer.

Williams SG, Millar JL, Duchesne GM, Dally MJ, Royce PL, Snow RM. · Department of Radiation Oncology, William Buckland Radiotherapy Centre, The Alfred Hospital, Commercial Road, Melbourne, Vic. 3004, Australia. · Radiother Oncol. · Pubmed #15465143 No free full text.

Abstract: PURPOSE: To assess factors related to the risk of acute urinary retention and other morbidity indices in patients undergoing transperineal seed implantation of the prostate. MATERIALS AND METHODS: One hundred and seventy-three consecutive patients treated with (125)Iodine transperineal interstitial permanent prostate brachytherapy (TIPPB) were evaluated. Various demographic, pathological, symptomatic, urodynamic and dosimetric values were assessed in relation to the incidence of acute urinary retention as well as the International Prostate Symptom Score (IPSS) dynamics. Patients were routinely placed on alpha-blockade postimplant. Dosimetry was based on CT scan one month postimplant. RESULTS: Acute urinary retention developed in thirty-four patients (19.7%), at a median time of four days. Peak urinary flow rate was the only independent factor which varied significantly between those suffering retention and those not (median of 16 and 19.5 ml/s respectively, P=0.005). Median preimplant IPSS was 4.0, with a median peak of 16 at 3 months. Actuarial median time to return to baseline IPSS was at 15 months. The peak IPSS above preimplant levels was correlated significantly in multivariate analysis with the number of seeds implanted superior to the physician-nominated anatomical base level of the prostate (P<0.009), as well as lower preimplant IPSS values. CONCLUSIONS: In our series, preimplant urinary flow rate was the most important factor predictive of postimplant acute urinary retention. The patients' risk of having heightened IPSS change following implantation was correlated to a lower preimplant IPSS and an increased number of seeds implanted above the level of the prostatic base, possibly reflecting bladder base rather than urethral irritation in the development of acute urinary morbidity.

Williams SG, Millar JL, Dally MJ, Sia S, Miles W, Duchesne GM. · William Buckland Radiotherapy Centre, The Alfred Hospital, Melbourne, Victoria, Australia. · Int J Radiat Oncol Biol Phys. · Pubmed #14697415 No free full text.

Abstract: PURPOSE: To assess the efficacy of a variety of prognostic models in the definition of intermediate-risk prostate cancer and to compare them to our own empiric model. METHODS AND MATERIALS: Two hundred fifty-six consecutive men with prostate adenocarcinoma treated with external beam radiotherapy alone were studied. Biochemical failure (defined as 3 consecutive PSA rises or the initiation of androgen deprivation therapy) was examined using univariate, multivariate, and recursive partitioning analyses. The risk classification model used in our department was then compared to a number of published models to assess the relative performance of each in discriminating risk groups. RESULTS: At a median follow-up of 62.4 months, the 5-year Biochemical failure-free survival (bFFS) was 46.8% for the overall group. This relates to 5-year bFFS of 77.8%, 51.1%, and 33.8% based on our institutional criteria for low-, intermediate-, and high-risk features, respectively. All the models examined showed an outcome group with a comparatively similar poor outcome when applied to our data. Large variation was seen in the intermediate-risk groups, with 5-year bFFS ranging from 38.1% to 51.1%. Good risk categories had similar large variations. All published models showed inability to delineate three significantly different outcome groups. Recursive partitioning analysis derived categories based on combinations of PSA (with cutpoints at 42.4, 20, and 10.6 ng/mL) and Gleason score (with cutpoints at 2-6 and 7-10) only. CONCLUSIONS: Large variations in the relative performance of a number of prognostic models are shown when applied to our local data. The prognostic efficacy of PSA and biopsy Gleason score is reiterated, although other factors will need to be explored to further improve the performance of prognostic models, particularly in defining the intermediate-risk subset of prostate cancer.

Duchesne GM, Millar JL, Moraga V, Rosenthal M, Royce P, Snow R. · Department of Radiation Oncology, The Alfred Hospital, Melbourne, Australia. · Int J Radiat Oncol Biol Phys. · Pubmed #12605977 No free full text.

Abstract: PURPOSE: To document current Australian management of asymptomatic prostate cancer patients with prostate-specific antigen (PSA) relapse after radical treatment or considered unsuitable for radical treatment. MATERIALS AND METHODS: Four case scenarios-postprostatectomy PSA relapse, postradiotherapy (RT) with a slow or a rapidly rising PSA level, or no radical treatment-were presented. Management preferences, including (where relevant) RT, androgen ablation either immediate or delayed until a PSA rise or symptomatic progression, and other approaches, were identified. The preferred methods of androgen ablation were noted. RESULTS: One hundred eighteen informative replies out of 324 e-mailed surveys were received. For postprostatectomy PSA relapse, 59% of respondents favored salvage RT. For post-RT with a slow or a rapidly rising PSA level and treatment of nonradical patients, there was no clear consensus of opinion, with respondents divided among the different options. A diverse range of PSA levels was cited for delayed intervention, with values ranging from 0.8 to 100 ng/mL. PSA doubling time proved a more consistent criterion for determining intervention. Most respondents favored the use of a luteinizing hormone-releasing hormone agonist as first-line androgen ablation, although patient choice was recognized as important in all decision making. CONCLUSIONS: A lack of available evidence underlies the diversity of opinion regarding the management of asymptomatic prostate cancer patients with a rising PSA. The need for randomized controlled trials in this area is highlighted.

Millar JL. · No affiliation provided · Urology. · Pubmed #18308135 No free full text.

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Millar JL, Sutherland JS, Boyd RL. · No affiliation provided · Int J Radiat Oncol Biol Phys. · Pubmed #17126227 No free full text.

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Millar JL. · No affiliation provided · Am J Health Syst Pharm. · Pubmed #10938976 No free full text.

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