Prostatic Neoplasms: Schellhammer P

Kramer BS, Hagerty KL, Justman S, Somerfield MR, Albertsen PC, Blot WJ, Ballentine Carter H, Costantino JP, Epstein JI, Godley PA, Harris RP, Wilt TJ, Wittes J, Zon R, Schellhammer P, Anonymous00093, Anonymous00094. · National Institutes of Health, Bethesda, MD, USA. · J Clin Oncol. · Pubmed #19252137 No free full text.

Abstract: PURPOSE To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. Results The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION Asymptomatic men with a prostate-specific antigen (PSA) <or= 3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.

Kramer BS, Hagerty KL, Justman S, Somerfield MR, Albertsen PC, Blot WJ, Carter HB, Costantino JP, Epstein JI, Godley PA, Harris RP, Wilt TJ, Wittes J, Zon R, Schellhammer P, Anonymous00066. · National Institutes of Health, Bethesda, MD, USA. · J Urol. · Pubmed #19249063 No free full text.

Abstract: PURPOSE: To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS: The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. RESULTS: The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION: Asymptomatic men with a prostate-specific antigen (PSA) </=3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.

Wilt TJ, MacDonald R, Hagerty K, Schellhammer P, Kramer BS. · VAMC, General Internal Medicine (111-0), One Veterans Drive, Minneapolis, Minnesota 55417, USA. · Cochrane Database Syst Rev. · Pubmed #18425978 No free full text.

Abstract: BACKGROUND: Five-alpha-reductase inhibitors (5ARI) are frequently used to treat bothersome lower urinary tract symptoms associated with benign prostatic hyperplasia and male androgenic alopecia. They have potential as chemopreventive agents. OBJECTIVES: We sought to estimate the effectiveness and harms of 5ARI in preventing prostate cancer. SEARCH STRATEGY: MEDLINE, PreMEDLINE, and the Cochrane Collaboration Library were searched through April 2007 to identify randomized trials. SELECTION CRITERIA: For prostate cancer outcomes we included randomized controlled trials of at least 1 year in duration published after 1984. For non-prostate cancer outcomes, randomized trials were included if: they were at least 6 months in duration published after 1999. DATA COLLECTION AND ANALYSIS: The primary outcome was prostate cancer period-prevalence "for-cause." "For-cause" was defined as prostate cancer clinically detected based on symptoms, an abnormal digital rectal exam, or detected as a result of an abnormal prostate specific antigen value. Trials were categorized as long (> 2 year), mid (1-2 years) and short (< 1 year) term. MAIN RESULTS: Nine trials reported prostate cancer period-prevalence. Three trials using finasteride lasted 4 years or longer but only one (the Prostate Cancer Prevention Trial) was specifically designed to assess the impact of 5ARI on prostate cancer period-prevalence. The mean age of enrollees was 64.6 years, 91% were white, mean PSA was 2.1 ng/mL. For-cause prostate cancers comprised 54% of all cancers detected. Finasteride was associated with a 26% relative risk reduction in prostate cancers detected for-cause among all randomized subjects (relative risk 0.74 [95% CI 0.67 to 0.83]; absolute risk reduction = 1.4% (3.5% versus 4.9%). Six trials assessed prostate cancers detected overall with a pooled 26% relative reduction favoring 5ARI (relative risk 0.74 [95% CI 0.55 to1.00]; 2.9% absolute reduction (6.3% versus 9.2%). Reductions were observed regardless of age, race or family history of prostate cancer but not among men with baseline PSA > 4.0 ng/mL. A greater number of high Gleason score tumors (7-10 or 8-10) occurred in men on finasteride in the PCPT. Impaired sexual or erectile function or endocrine effects were more common with finasteride than placebo. AUTHORS' CONCLUSIONS: 5ARI reduce prostate cancer risk but may increase the risk of high-grade disease in men who are undergoing regular screening for prostate cancer using prostate specific antigen and digital rectal examination. Effects are consistent across race, family history and age and possibly 5ARI but were limited to men with baseline PSA values <4.0 ng/mL. The impact of 5ARI on absolute or relative rates of prostate cancer in men who are not being regularly screened is not clear. Information is inadequate to assess the impact of 5ARI on mortality.

McKoy JM, Lyons EA, Obadina E, Carson K, Pickard AS, Schellhammer P, McLeod D, Boyd CE, McWilliams N, Sartor O, Schumock GT, McCaffery K, Bennett CL. · Jesse Brown Veterans Affairs Medical Center Lakeside Community-Based Outpatient Clinic, IL, USA. · J Clin Oncol. · Pubmed #16314650 No free full text.

Abstract: In the course of recent health care fraud investigations against TAP Pharmaceuticals (Lake Forest, IL) and AstraZeneca International (London, United Kingdom), each pled guilty to one violation of the Prescription Drug Marketing Act, settled claims related to alleged violations of the False Claims Act without admitting guilt, and paid fines, settlements for liabilities, and reimbursements of dollar 850 million and dollar 355 million, respectively. In a unique aspect of these cases, federal investigators brought criminal charges against 14 TAP employees and investigated the billing practices of several urologists. These investigations resulted in guilty pleas from both urologists and industry employees relative to the Prescription Drug Marketing Act or the False Claims Act and probationary sentences with payments of fines and restitution to the government for urologists who cooperated with federal investigations. One uncooperative urologist was found guilty of violating the Federal False Claims Act and sentenced to 6 months of home arrest, excluded from Medicare for 5 years, required to provide 600 hours of free medical care to indigent patients and patients covered by Medicare or Medicaid, and paid fines and restitution to the government. The cases against TAP and AstraZeneca have been followed by federal and state investigations of allegedly illegal marketing practices of other pharmaceutical firms and have resulted in negotiated settlements of dollar 3.8 billion and dollar 71.5 million, respectively. Believing that an Average Wholesale Price-based reimbursement system was an important driving factor for these marketing activities, Medicare has shifted to an Average Sales Price-based reimbursement system. This is expected to greatly impact the practice of outpatient oncology nationwide.

Klotz L, Schellhammer P. · Sunnybrook and Women's College Health Sciences Centre University of Toronto, Canada. · Clin Prostate Cancer. · Pubmed #15882477 No free full text.

Abstract: Combination therapy consists of castration plus an antiandrogen. Following medical or surgical castration, the androgen receptor can be activated by adrenal androgens, low levels of residual testosterone, and ligand-independent activators. The survival benefit of combination therapy compared with castration alone is one of the most studied questions in urology. Results from trials comparing combination therapy to castration alone are variable. A metaanalysis of 26 randomized trials indicated that the type of antiandrogen used is relevant. Combination therapy using nonsteroidal antiandrogens was associated with a statistically significant overall survival benefit. In contrast, combination therapy using steroidal antiandrogens was associated with reduced survival compared with castration alone. Bicalutamide 50 mg has a number of advantages compared with nilutamide and flutamide when used in combination with castration. These include an improved side-effect profile, once-daily dosing, more potent inhibition of androgen-independent activation of the androgen receptor through favorable interactions with nuclear coactivators and corepressors, and evidence for improved survival in one randomized trial. An analysis combining historic trial data suggests that bicalutamide 50 mg in addition to androgen deprivation may reduce the hazard ratio (HR) for prostate cancer mortality by 20% (HR, 0.80; 95% CI, 0.66-0.98).

Klotz L, Schellhammer P, Carroll K. · Sunnybrook & Women's College Health Sciences Centre, University of Toronto, Canada. · BJU Int. · Pubmed #15180600 No free full text.

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Carroll P, Coley C, McLeod D, Schellhammer P, Sweat G, Wasson J, Zietman A, Thompson I. · Department of Urology, University of California, San Francisco, Medical Center, San Francisco, California, USA. · Urology. · Pubmed #11182325 No free full text.

This publication has no abstract.

Taylor JH, Davis J, Schellhammer P. · Department of Urology, Eastern Virginia Medical School, Norfolk, VA 23501, USA. · Clin Genitourin Cancer. · Pubmed #17956711 No free full text.

Abstract: BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) is a treatment option for superficial (<or=T1) transitional cell carcinoma. Transitional cell carcinoma involving the prostatic urethra presents a treatment dilemma. Whereas prostatic urethral involvement might require radical cystectomy, select patients can be offered BCG and careful surveillance to preserve the bladder. We report long-term experience with BCG in this subset of patients with >5-year follow-up. PATIENTS AND METHODS: Twenty-eight patients with high-risk superficial bladder cancer and prostatic urethral involvement were treated with once-weekly BCG for 6 weeks. Patients with prostatic stromal involvement were excluded. Maintenance was not used before 1995. Currently, we use maintenance BCG after induction. Patients were followed by cystoscopy/cytology and repeat biopsy to detect persistent and/or progressive disease. RESULTS: After 1 or 2 courses of once-weekly BCG for 6 weeks, 64.3% (18 of 28 of patients) exhibited a complete response in the bladder and prostate at their 6-month followup. Of those obtaining a complete response, 55.6% (10 of 18) experienced recurrence. Three recurrences were in the prostate: 1 isolated and 2 associated with multifocal bladder involvement. Twenty-eight percent (8 of 28 patients) underwent cystectomy because of failure of treatment to eradicate superficial disease or disease progression. Disease-specific survival was 89% (25 of 28 patients) at a median follow-up of 7.5 years. CONCLUSION: Our long-term data support the durability of intravesical BCG in select patients with superficial bladder transitional cell carcinoma with prostatic urethral involvement. Follow-up biopsy of the prostatic urethra is mandatory and, if positive, cystectomy is indicated. One third of patients will require cystectomy for persistent or progressive disease; therefore, careful surveillance is critical.

Roach M, Hanks G, Thames H, Schellhammer P, Shipley WU, Sokol GH, Sandler H. · Department of Radiation Oncology, University of California San Francisco, San Francisco, CA 94143-1708, and Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #16798415 No free full text.

Abstract: In 1996 the American Society for Therapeutic Radiology and Oncology (ASTRO) sponsored a Consensus Conference to establish a definition of biochemical failure after external beam radiotherapy (EBRT). The ASTRO definition defined prostate specific antigen (PSA) failure as occurring after three consecutive PSA rises after a nadir with the date of failure as the point halfway between the nadir date and the first rise or any rise great enough to provoke initiation of therapy. This definition was not linked to clinical progression or survival; it performed poorly in patients undergoing hormonal therapy (HT), and backdating biased the Kaplan-Meier estimates of event-free survival. A second Consensus Conference was sponsored by ASTRO and the Radiation Therapy Oncology Group in Phoenix, Arizona, on January 21, 2005, to revise the ASTRO definition. The panel recommended: (1) a rise by 2 ng/mL or more above the nadir PSA be considered the standard definition for biochemical failure after EBRT with or without HT; (2) the date of failure be determined "at call" (not backdated). They recommended that investigators be allowed to use the ASTRO Consensus Definition after EBRT alone (no hormonal therapy) with strict adherence to guidelines as to "adequate follow-up." To avoid the artifacts resulting from short follow-up, the reported date of control should be listed as 2 years short of the median follow-up. For example, if the median follow-up is 5 years, control rates at 3 years should be cited. Retaining a strict version of the ASTRO definition would allow comparisons with a large existing body of literature.

Schellhammer P. · Department of Urology, Eastern Virginia Medical School, Norfolk, Virginia, USA. · BJU Int. · Pubmed #12887463 No free full text.

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Zietman AL, Thakral H, Wilson L, Schellhammer P. · Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. · J Urol. · Pubmed #11586206 No free full text.

Abstract: 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.

Carroll P, Coley C, McLeod D, Schellhammer P, Sweat G, Wasson J, Zietman A, Thompson I. · Department of Urology, University of California, San Francisco, Medical Center, San Francisco, California, USA. · Urology. · Pubmed #11182324 No free full text.

This publication has no abstract.

Perez CA, Beyer DC, Blasko JC, Forman JD, Hussey DH, Lee WR, Paryani SB, Pollack A, Potters L, Roach M, Scardino P, Schellhammer P, Leibel S. · Mallinckrodt Institute of Radiology, St. Louis, Mo., USA. · Radiology. · Pubmed #11037559 No free full text.

This publication has no abstract.

Roach M, Blasko JC, Perez CA, Beyer DC, Forman JD, Hussey DH, Lee WR, Paryani SB, Pollack A, Potters L, Scardino P, Schellhammer P, Leibel S. · University of California, San Francisco, USA. · Radiology. · Pubmed #11037558 No free full text.

This publication has no abstract.

Perez CA, Beyer DC, Blasko JC, Forman JD, Hussey DH, Lee WR, Paryani SB, Pollack A, Potters L, Roach M, Scardino P, Schellhammer P, Leibel S. · Mallinckrodt Institute of Radiology, St. Louis, Mo., USA. · Radiology. · Pubmed #11037557 No free full text.

This publication has no abstract.

Lee WR, Pollack A, Perez CA, Beyer DC, Blasko JC, Forman JD, Hussey DH, Paryani SB, Potters L, Roach M, Scardino P, Schellhammer P, Leibel S. · Wake Forest University School of Medicine, Winston Salem, NC, USA. · Radiology. · Pubmed #11037556 No free full text.

This publication has no abstract.

Pollack A, Paryani SB, Hussey D, Perez CA, Beyer DC, Blasko JC, Forman JD, Lee WR, Potters L, Roach M, Scardino P, Schellhammer P, Leibel S. · University of Texas, M.D. Anderson Cancer Center, Houston, USA. · Radiology. · Pubmed #11037555 No free full text.

This publication has no abstract.

Potters L, Perez CA, Beyer DC, Blasko JC, Forman JD, Hussey DH, Lee WR, Paryani SB, Pollack A, Roach M, Scardino P, Schellhammer P, Leibel S. · Memorial Sloan-Kettering Cancer Center, Mercy Medical Center, Rockville Centre, NY, USA. · Radiology. · Pubmed #11037554 No free full text.

This publication has no abstract.

Forman JD, Lee WR, Roach M, Perez CA, Beyer DC, Blasko JC, Hussey DH, Paryani SB, Pollack A, Potters L, Scardino P, Schellhammer P, Leibel S. · Harper Grace Hospital, Detroit, Mich., USA. · Radiology. · Pubmed #11037553 No free full text.

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Schellhammer P, Fabozzi S. · No affiliation provided · Urology. · Pubmed #10414752 No free full text.

This publication has no abstract.