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Re: Risk of Colorectal Cancer in Men on Long-Term Androgen Deprivation Therapy for Prostate Cancer
904
PROSTATE CANCER
Disease-Free Survival Following Salvage Cryotherapy for Biopsy-Proven Radio-Recurrent Prostate Cancer A. K. Williams, C. H. Martínez, C. Lu, C. K. Ng, S. E. Pautler and J. L. Chin Departments of Urology and Oncology, University of Western Ontario, London, Ontario, Canada Eur Urol 2010; Epub ahead of print.
Background: The optimum treatment of prostate cancer recurrence following radiation therapy (RT) remains controversial due to the lack of long-term data. Objective: Our aim was to review the survival of patients who underwent salvage cryotherapy to the prostate gland for biopsy-proven recurrent prostate cancer and establish prognostic indicators. Design, Setting, and Participants: A retrospective analysis was performed on all patients undergoing salvage cryotherapy at an academic urology unit for biopsy-proven locally recurrent prostate cancer after RT from 1995 to 2004. Patients’ preoperative, perioperative, and postoperative data were reviewed and recorded. Intervention: Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon. Measurements: The primary outcome was survival. Secondary outcomes were disease-free survival (DFS), metastasis-free survival, and progression to androgen-deprivation therapy. Results and Limitations: Of 187 patients, 176 had records available for follow-up (follow-up rate: 94%). Mean follow-up was 7.46 yr (range: 1-14 yr). Fifty-two patients were followed for ⬎10 yr. DFS at 10 yr was 39%. Risk factors for recurrence were presalvage prostate-specific antigen (PSA), preradiation, and presalvage Gleason score. A PSA nadir ⬎1.0 ng/dl was highly predictive of early recurrence. Conclusions: Salvage cryotherapy led to an acceptable 10-yr DFS. Presalvage PSA and Gleason score were the best predictors of disease recurrence. A PSA nadir ⬎1 ng/dl following cryotherapy indicated a poor prognosis, and recurrence of disease was universal in these patients. Editorial Comment: Although I have never been enthusiastic about advising salvage cryotherapy for patients who have recurrence following radiation therapy, I learned from this article who should not receive it. These authors report that men who had a PSA greater than 10 ng/ml at the time of recurrence were not good candidates because treatment was unlikely to control their disease. Conversely although men with Gleason scores of 7 or higher on their presalvage biopsy had a higher risk of recurrence than patients with lower scores, the failure rate in patients with Gleason scores 7, 8 or 9 were still acceptable at 33%. Patrick C. Walsh, M.D.
Re: Risk of Colorectal Cancer in Men on Long-Term Androgen Deprivation Therapy for Prostate Cancer S. Gillessen, A. Templeton, G. Marra, Y. F. Kuo, E. Valtorta and V. B. Shahinian Department of Medical Oncology, Kantonsspital, St. Gallen, Switzerland J Natl Cancer Inst 2010; 102: 1760 –1770.
Background: Androgen deprivation with gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is a common but controversial treatment for prostate cancer. Uncertainties remain about its use, particularly with increasing recognition of serious side effects. In animal studies, androgens protect against colonic carcinogenesis, suggesting that androgen deprivation may increase the risk of colorectal cancer. Methods: We identified 107x859 men in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were diagnosed with prostate cancer in 1993 through 2002, with follow-up available through 2004. The primary outcome was development of colorectal cancer, determined from SEER files on second primary cancers. Cox proportional hazards regression was used to assess the influence of androgen deprivation on the outcome, adjusted for patient and prostate cancer characteristics. All statistical tests were two-sided. Results: Men who had orchiectomies had the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95% confidence interval [CI] ⫽ 5.3 to 7.5), followed by men who had GnRH agonist therapy (4.4 per 1000 person-years; 95% CI ⫽ 4.0 to 4.9), and men who had no androgen deprivation (3.7 per 1000
TESTIS CANCER
905
person-years; 95% CI ⫽ 3.5 to 3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose-response effect (P(trend) ⫽ .010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (hazard ratio [HR] ⫽ 1.31, 95% CI ⫽ 1.12 to 1.53) or with orchiectomy (HR ⫽ 1.37, 95% CI ⫽ 1.14 to 1.66). Conclusion: Long-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cancer. Editorial Comment: We can now add a new side effect to the list of complications following long-term androgen deprivation— colorectal cancer. This study showed a 30% to 40% relative increase in the rate of colorectal cancer among men treated with androgen deprivation. The longer they received it, the greater their risk. Patrick C. Walsh, M.D.
Urological Oncology: Testis Cancer Organ-Sparing Surgery for Adult Testicular Tumours: A Systematic Review of the Literature G. Giannarini, K. P. Dieckmann, P. Albers, A. Heidenreich and G. Pizzocaro Department of Urology, University of Pisa, Pisa, Italy Eur Urol 2010; 57: 780 –790.
Context: According to current guidelines, radical orchidectomy is the standard treatment for testis tumours of malignant and unknown origin. Testis-sparing surgery (TSS) has recently been proposed as an alternative option in selected cases. Objective: Our aim was to analyse the cumulative evidence for TSS in the treatment of adult malignant tumours of different histology, including notes on operative technique, indications, complications, and oncologic and functional outcome. Evidence Acquisition: A systematic literature search of the Medline/PubMed database for full-length papers reporting on TSS for adult malignant tumours was performed up to September 2009. Bibliographies of retrieved articles and review articles were also examined. Only those articles with complete data on operative technique, complications, and oncologic or functional outcome were selected. Furthermore, published abstracts at major urologic meetings in the last decade (1999 –2009) and guidelines on testis cancer from major oncologic and urologic medical associations were searched and evaluated. Evidence Synthesis: No randomised controlled trials have compared TSS and radical orchidectomy; only retrospective outcome studies and case reports on TSS are available. In patients with small malignant germ cell tumours arising in both or in solitary testes, TSS coupled with local adjuvant radiotherapy ensures good oncologic control and is associated with a preserved endocrine function in most cases. In patients with small Leydig cell tumours, TSS can also be performed with elective indications (healthy contralateral testes), provided that pathology fails to reveal aggressive features. Finally, TSS is an option for patients with small ultrasound-detected, nonpalpable tumours even with elective indications because the incidence of benign definitive histology is high at approximately 80%. The overall complication rate is low (⬍6%). Data on exocrine and endocrine gonadal function, male body image, and health-related quality of life after TSS are still immature. Conclusions: TSS can be safely adopted for the treatment of carefully selected cases of tumours of different histology. Prospective multicentre studies are warranted to further qualify TSS as a treatment option to be recommended as an alternative to radical orchidectomy and to explore the perceived functional advantages of testis preservation. Editorial Comment: Improvements in imaging of the testis, especially high frequency scrotal ultrasound, have resulted in identification of smaller intratesticular lesions,
PROSTATE CANCER
Disease-Free Survival Following Salvage Cryotherapy for Biopsy-Proven Radio-Recurrent Prostate Cancer A. K. Williams, C. H. Martínez, C. Lu, C. K. Ng, S. E. Pautler and J. L. Chin Departments of Urology and Oncology, University of Western Ontario, London, Ontario, Canada Eur Urol 2010; Epub ahead of print.
Background: The optimum treatment of prostate cancer recurrence following radiation therapy (RT) remains controversial due to the lack of long-term data. Objective: Our aim was to review the survival of patients who underwent salvage cryotherapy to the prostate gland for biopsy-proven recurrent prostate cancer and establish prognostic indicators. Design, Setting, and Participants: A retrospective analysis was performed on all patients undergoing salvage cryotherapy at an academic urology unit for biopsy-proven locally recurrent prostate cancer after RT from 1995 to 2004. Patients’ preoperative, perioperative, and postoperative data were reviewed and recorded. Intervention: Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon. Measurements: The primary outcome was survival. Secondary outcomes were disease-free survival (DFS), metastasis-free survival, and progression to androgen-deprivation therapy. Results and Limitations: Of 187 patients, 176 had records available for follow-up (follow-up rate: 94%). Mean follow-up was 7.46 yr (range: 1-14 yr). Fifty-two patients were followed for ⬎10 yr. DFS at 10 yr was 39%. Risk factors for recurrence were presalvage prostate-specific antigen (PSA), preradiation, and presalvage Gleason score. A PSA nadir ⬎1.0 ng/dl was highly predictive of early recurrence. Conclusions: Salvage cryotherapy led to an acceptable 10-yr DFS. Presalvage PSA and Gleason score were the best predictors of disease recurrence. A PSA nadir ⬎1 ng/dl following cryotherapy indicated a poor prognosis, and recurrence of disease was universal in these patients. Editorial Comment: Although I have never been enthusiastic about advising salvage cryotherapy for patients who have recurrence following radiation therapy, I learned from this article who should not receive it. These authors report that men who had a PSA greater than 10 ng/ml at the time of recurrence were not good candidates because treatment was unlikely to control their disease. Conversely although men with Gleason scores of 7 or higher on their presalvage biopsy had a higher risk of recurrence than patients with lower scores, the failure rate in patients with Gleason scores 7, 8 or 9 were still acceptable at 33%. Patrick C. Walsh, M.D.
Re: Risk of Colorectal Cancer in Men on Long-Term Androgen Deprivation Therapy for Prostate Cancer S. Gillessen, A. Templeton, G. Marra, Y. F. Kuo, E. Valtorta and V. B. Shahinian Department of Medical Oncology, Kantonsspital, St. Gallen, Switzerland J Natl Cancer Inst 2010; 102: 1760 –1770.
Background: Androgen deprivation with gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is a common but controversial treatment for prostate cancer. Uncertainties remain about its use, particularly with increasing recognition of serious side effects. In animal studies, androgens protect against colonic carcinogenesis, suggesting that androgen deprivation may increase the risk of colorectal cancer. Methods: We identified 107x859 men in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were diagnosed with prostate cancer in 1993 through 2002, with follow-up available through 2004. The primary outcome was development of colorectal cancer, determined from SEER files on second primary cancers. Cox proportional hazards regression was used to assess the influence of androgen deprivation on the outcome, adjusted for patient and prostate cancer characteristics. All statistical tests were two-sided. Results: Men who had orchiectomies had the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95% confidence interval [CI] ⫽ 5.3 to 7.5), followed by men who had GnRH agonist therapy (4.4 per 1000 person-years; 95% CI ⫽ 4.0 to 4.9), and men who had no androgen deprivation (3.7 per 1000
TESTIS CANCER
905
person-years; 95% CI ⫽ 3.5 to 3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose-response effect (P(trend) ⫽ .010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (hazard ratio [HR] ⫽ 1.31, 95% CI ⫽ 1.12 to 1.53) or with orchiectomy (HR ⫽ 1.37, 95% CI ⫽ 1.14 to 1.66). Conclusion: Long-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cancer. Editorial Comment: We can now add a new side effect to the list of complications following long-term androgen deprivation— colorectal cancer. This study showed a 30% to 40% relative increase in the rate of colorectal cancer among men treated with androgen deprivation. The longer they received it, the greater their risk. Patrick C. Walsh, M.D.
Urological Oncology: Testis Cancer Organ-Sparing Surgery for Adult Testicular Tumours: A Systematic Review of the Literature G. Giannarini, K. P. Dieckmann, P. Albers, A. Heidenreich and G. Pizzocaro Department of Urology, University of Pisa, Pisa, Italy Eur Urol 2010; 57: 780 –790.
Context: According to current guidelines, radical orchidectomy is the standard treatment for testis tumours of malignant and unknown origin. Testis-sparing surgery (TSS) has recently been proposed as an alternative option in selected cases. Objective: Our aim was to analyse the cumulative evidence for TSS in the treatment of adult malignant tumours of different histology, including notes on operative technique, indications, complications, and oncologic and functional outcome. Evidence Acquisition: A systematic literature search of the Medline/PubMed database for full-length papers reporting on TSS for adult malignant tumours was performed up to September 2009. Bibliographies of retrieved articles and review articles were also examined. Only those articles with complete data on operative technique, complications, and oncologic or functional outcome were selected. Furthermore, published abstracts at major urologic meetings in the last decade (1999 –2009) and guidelines on testis cancer from major oncologic and urologic medical associations were searched and evaluated. Evidence Synthesis: No randomised controlled trials have compared TSS and radical orchidectomy; only retrospective outcome studies and case reports on TSS are available. In patients with small malignant germ cell tumours arising in both or in solitary testes, TSS coupled with local adjuvant radiotherapy ensures good oncologic control and is associated with a preserved endocrine function in most cases. In patients with small Leydig cell tumours, TSS can also be performed with elective indications (healthy contralateral testes), provided that pathology fails to reveal aggressive features. Finally, TSS is an option for patients with small ultrasound-detected, nonpalpable tumours even with elective indications because the incidence of benign definitive histology is high at approximately 80%. The overall complication rate is low (⬍6%). Data on exocrine and endocrine gonadal function, male body image, and health-related quality of life after TSS are still immature. Conclusions: TSS can be safely adopted for the treatment of carefully selected cases of tumours of different histology. Prospective multicentre studies are warranted to further qualify TSS as a treatment option to be recommended as an alternative to radical orchidectomy and to explore the perceived functional advantages of testis preservation. Editorial Comment: Improvements in imaging of the testis, especially high frequency scrotal ultrasound, have resulted in identification of smaller intratesticular lesions,