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Prostate Cancer Recurrence in Kidney Transplant Recipient 15 Years After Radical Prostatectomy: A Case Report
Prostate Cancer Recurrence in Kidney Transplant Recipient 15 Years After Radical Prostatectomy: A Case Report Daniele Sforzaa,*, Alessandro Parentea, Marco Pellicciaroa, Marika Morabitoa, Giuseppe Iariaa, Alessandro Anselmoa, Elisa Rossi Lindforsa, Federica Corradoa, Chiara Cacciatorea, Dario Del Fabbrob, Gianluca Ingrossoc, and Giuseppe Tisonea a Department of Hepatobiliary Surgery and Transplant Unit, Tor Vergata University of Rome, Italy; bUrology Unit, Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy; and cDiagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy Unit, Tor Vergata University of Rome, Rome, Italy
ABSTRACT Incidence of malignant tumors in kidney transplant recipients is higher than nontransplanted population due to many factors, such as immunosuppression therapy and complex donorrecipient interaction. Genitourinary malignancies have been reported as the second most common malignancy in kidney transplant recipients. In this regard, prostate cancer is the most common neoplasm. Herein, we describe a rare case of prostate cancer recurrence after 15 years in a patient who underwent kidney transplant after radical prostatectomy.
R
ENAL transplantation is considered as the best therapeutic option for end-stage renal disease. Incidence of malignant tumor in renal transplanted recipients (RTRs) results increased due to many factors, such as impaired immunosurveillance, oncogenic viruses, complex donor-recipient interaction, and, possibly, direct neoplastic action of some immunosuppressive therapy. RTRs have about a 4- to 20-fold higher risk of de novo cancer occurrence compared with the general population [1-3]. Genitourinary malignancies have been reported as the second most common malignancy in RTRs in the United States; among these, prostate cancer (PCa) is the most frequent, with a 3-year cumulative incidence of about 2.5%. The incidence of PCa in RTRs has historically been underestimated, with a commonly accepted greater risk from a 2- to 5-fold greater risk compared to the general population [4]. If the tumor is diagnosed, several treatment options are available for PCa, including radical prostatectomy (RP), radiotherapy (RT), and androgen deprivation therapy alone or in combination, but the recurrence rate remains high regardless of the type of treatment [5]. A recurrence-free period of 2 to 5 years is usually requested in RTRs affected by previous neoplasms to minimize post-transplant recurrence risk. The aim of this paper is to describe a rare case of PCa recurrence after 15 years in a patient who underwent kidney transplant after radical prostatectomy. CASE REPORT A 72-year-old man with end-stage renal disease of unknown etiology was referred in our center in order to be evaluated as a ª 2019 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, XX, 1e3 (2019)
candidate for kidney transplant (KT) from a deceased donor. His general condition was good, without major comorbidities, just arterial hypertension under medical treatment. He had a medical history, at the age of 59 years, of former radical prostatectomy due to prostate adenocarcinoma (histology: G3-G4, Gleason 8; pT2c, N0, M0). Thus, he underwent a kidney transplant when he was 72 years old; the graft was located in right iliac fossa. As induction therapy, he received basiliximab on the first and fourth day after surgery in combination with steroids, tacrolimus, and mycophenolic acid. Within the 10th postoperative day, steroids were progressively withdrawn. He had a delayed graft function that, however, resolved within 1 month, ending in a good graft function (creatinine 1.5 mg/ dL, estimated glomerular filtration rate 53 mL/min/1.73 m2 at 30th postoperative day). During the follow-up, prostate specific antigen (PSA) was constantly monitored and was undetectable until 31 months after KT; 2 years after the transplant, he presented in good clinical status with a good graft function, but his serum PSA level was increased to 5.1 ng/mL. The case was discussed in a multidisciplinary meeting between transplant surgeons, urologists, radiologists, and oncologists in order to decide the therapeutic approach. A choline-positron emission tomography/computed tomography (PET/CT) total body was performed, showing an increased uptake in a right pararectal obturator lymph node (23 mm diameter), diagnostic for PCa recurrence. At this time, patient immunosuppressive therapy was tacrolimus (2.5 mg once a day of prolonged release formulation) and mycophenolic acid (360 mg twice a day). *Address correspondence to Daniele Sforza, MD, PhD, Department of Hepatobiliary Surgery and Transplant Unit, University of Rome “Tor Vergata,” Italy, Policlinico Tor Vergata, Viale Oxford, 81, 00133 Rome, Italy. Tel: 0039 0620901, Fax: 0039 06.2090.0018. E-mail: [email protected] 0041-1345/19 https://doi.org/10.1016/j.transproceed.2019.04.098
1
2 After the diagnosis of tumor recurrence, the dose of mycophenolic acid was reduced to 180 mg twice a day, and tacrolimus was switched to everolimus 0.5 mg twice a day. Targeted RT was started, at which time the serum PSA level was 7.63 ng/mL, creatinine 1.1. mg/dL, and estimated glomerular filtration rate 65 mL/min/1.73 m2. RT ended after 6 months: the serum PSA level was undetectable, and both choline-PET/CT total body and magnetic resonance results were negative for cancer recurrence. Four years after RT, the graft function remains stable, without signs of PCa recurrence.
MATERIALS AND METHODS Three different investigators (M.M., M.P., A.P.) searched, independently, in PubMed, Google Scholar, and Transplant Library for all the literature regarding prostate cancer recurrence in renal transplant recipients from 1990 since early 2018. Key words were “prostate cancer recurrence," “renal transplant recipients," “kidney transplant," “radiotherapy," “fluorocholine pet," and “prostate specific antigen.” A fourth investigator (D.S.) reviewed all the papers selected.
DISCUSSION
The true incidence of PCa in RTRs is difficult to determine because most transplant registry data were obtained before the existence of systematic screening for this disease [6]. PCa is the second most common cause of cancer death in the United States; it is highly age dependent and is most commonly diagnosed after the age of 50 (with the median age of diagnosis being 71 years). The PCa diagnoses will increase in male renal transplant patients with the increasing use of screening tests. The literature has no homogeneous series of RTRs with relatively high prevalence of PCa [7-9]. Although there is no solid evidence of higher incidence of PCa in RTRs, this may be a challenging event since there are no specific guidelines for treatment of these patients, whose prognosis is worsened. Many studies concluded that RTRs have a low but real risk of cancer recurrence and cancer-related death. Low-risk patients may be candidates for transplantation after 2 years without recurrence, while stage III disease patients should have at least a 5-year disease-free period before transplantation [10,11]. In nonimmunosuppressed patients, radiation and surgery are considered potentially curative in localized PCa with roughly equivalent cure rates at 10 years, but surgery may be associated with higher survival at 15 years. In the surgery setting of future KT, retropubic radical prostatectomy can complicate the placement of future renal transplant by causing extraperitoneal fibrosis, whereas the perineal approach preserves the bladder and both iliac fossa for further transplant [12]. Although RP could cause critical surgical problems during transplantation, it is associated with a shorter waiting list, and it ensures the best oncological prognosis both before and after kidney transplantation [10]. There is no uniform definition for “biochemical relapse;” generally, a patient who has undergone RP should have no remaining nonmalignant PSA-producing tissue. Both the American Urological Association and American Society of Radiation Oncology guidelines and the European
SFORZA, PARENTE, PELLICCIARO ET AL
Association of Urology guidelines describe biochemical postprostatectomy recurrence as a detectable or rising PSA value > 0.2 ng/mL with a second confirmation level > 0.2 ng/mL [13e16]. Evidence suggests that choline PET/CT can be helpful for the evaluation of locoregional and distant metastatic disease in men with increasing PSA level, increasing PSA velocity, and decreasing PSA doubling time [17]. In general, choline PET/CT has a low to modest sensitivity and a high specificity for detecting involved nodes in the pelvic region [14,15]. After detection of PCa relapse, it is critical to choose the correct therapy. RT has demonstrated to be helpful and well tolerated in RTRs [18]. It has been suggested that the pharmacologic therapy in RTRs, such as corticosteroids and immunosuppressive drugs, can further increase the risk of RT side effects. It is important that the dose delivered to the graft remains minimal, possibly below the threshold, to affect renal function. Furthermore, checking for a full bladder before irradiation in RTRs may provide a simple but effective means on reducing the risk of late side effects to the donor ureter [19]. CONCLUSIONS
An adequate oncologic follow-up is crucial in kidney transplanted patients with a history of PCa, even after several years of being disease free. Furthermore, we believe that a multidisciplinary approach is paramount in the management of PCa recurrence in the renal transplanted population. REFERENCES [1] Lilja H, Christensson A, Dahlen U, et al. Prostate-specific antigen in serum occurs predominantly in complex with alpha 1antichymotrypsin. Clin Chem. 1991;37:1618e1625. [2] Christensson A, Bjbrk T, Nilsson O, et al. Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J Urol. 1993;150:100e105. [3] Partin AW, Piantadosi S, Subong EN, et al. Clearance rate of serum-free and total PSA following radical retropubic prostatectomy. Prostate Suppl. 1996;7:35e39. [4] Keinclauss FM, Neuzillet Y, Tillou X, et al. Morbidity of retropubic radical prostatectomy for prostate cancer in renal transplant recipients: multicenter study from Renal Transplantation Committee of French Urological Association. Urology. 2008;72: 1366e1370. [5] Beauval JB, Roumiguié M, Filleron T, et al. Biochemical recurrence-free survival and pathological outcomes after radical prostatectomy for high-risk prostate cancer. BMC Urol. 2016;16:26. [6] Penn I. Post-transplant malignancy: the role of immunosuppression. Drug Saf. 2000;23:101e113. [7] Diller R, Gruber A, Wolters H, et al. Therapy and prognosis of tumors of the genitourinary tract after kidney transplantation. Transplant Proc. 2005;37:2089e2092. [8] Cormier L, Lechevallier E, Barrou B, et al. Diagnosis and treatment of prostate cancers in renal transplant recipients. Transplantation. 2003;75:237e239. [9] Malavaud B, Hoff M, Meidouge M, et al. PSA-based screening for prostate cancer after renal transplant. Transplantation. 2000;69:2461e2462. [10] Chahwan C, Doerfler A, Brichart N, et al. Prostate cancer before renal transplantation: a multicentre study. Progrès en urologie. 2017;27:166e175.
PROSTATE CANCER RECURRENCE [11] Tillou X, Chahwan C, Le Gal Sophie, et al. Prostatectomy for localized prostate cancer to prepare for renal transplantation in end-stage renal disease patients. Ann Transplant. 2014;19: 569e575. [12] Yiou R, Salomon L, Colombel M, et al. Perineal approach to radical prostatectomy in kidney transplant recipients with localized prostate cancer. Urology. 1999;53:822e824. [13] Evangelista L, Zattoni F, Rossi E. Early detection of prostate cancer relapse by biochemistry and diagnostic imaging. Q J Nucl Med Mol Imaging. 2015;59:359e373. [14] Thompson IM, Valicenti RK, Albertsen P, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline. J Urol. 2013;190:441e449.
3 [15] Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014;65:467e479. [16] Lilja H, Ulmert D, Vickers AJ. Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer. 2008;8:268e278. [17] Jadvar J. Molecular imaging of prostate cancer with PET. J Nucl Med. 2013;54:1685e1688. [18] Binsaleh S. Diagnosis and treatment of prostate cancer in renal-transplant recipients. Int Urol Nephrol. 2012;44:149e155. [19] Mouzin M, Bachaud JM, Kamar N, et al. Three-dimensional conformal radiotherapy for localized prostate cancer in kidney transplant recipients. Transplantation. 2004;78:1496e1500.
ABSTRACT Incidence of malignant tumors in kidney transplant recipients is higher than nontransplanted population due to many factors, such as immunosuppression therapy and complex donorrecipient interaction. Genitourinary malignancies have been reported as the second most common malignancy in kidney transplant recipients. In this regard, prostate cancer is the most common neoplasm. Herein, we describe a rare case of prostate cancer recurrence after 15 years in a patient who underwent kidney transplant after radical prostatectomy.
R
ENAL transplantation is considered as the best therapeutic option for end-stage renal disease. Incidence of malignant tumor in renal transplanted recipients (RTRs) results increased due to many factors, such as impaired immunosurveillance, oncogenic viruses, complex donor-recipient interaction, and, possibly, direct neoplastic action of some immunosuppressive therapy. RTRs have about a 4- to 20-fold higher risk of de novo cancer occurrence compared with the general population [1-3]. Genitourinary malignancies have been reported as the second most common malignancy in RTRs in the United States; among these, prostate cancer (PCa) is the most frequent, with a 3-year cumulative incidence of about 2.5%. The incidence of PCa in RTRs has historically been underestimated, with a commonly accepted greater risk from a 2- to 5-fold greater risk compared to the general population [4]. If the tumor is diagnosed, several treatment options are available for PCa, including radical prostatectomy (RP), radiotherapy (RT), and androgen deprivation therapy alone or in combination, but the recurrence rate remains high regardless of the type of treatment [5]. A recurrence-free period of 2 to 5 years is usually requested in RTRs affected by previous neoplasms to minimize post-transplant recurrence risk. The aim of this paper is to describe a rare case of PCa recurrence after 15 years in a patient who underwent kidney transplant after radical prostatectomy. CASE REPORT A 72-year-old man with end-stage renal disease of unknown etiology was referred in our center in order to be evaluated as a ª 2019 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, XX, 1e3 (2019)
candidate for kidney transplant (KT) from a deceased donor. His general condition was good, without major comorbidities, just arterial hypertension under medical treatment. He had a medical history, at the age of 59 years, of former radical prostatectomy due to prostate adenocarcinoma (histology: G3-G4, Gleason 8; pT2c, N0, M0). Thus, he underwent a kidney transplant when he was 72 years old; the graft was located in right iliac fossa. As induction therapy, he received basiliximab on the first and fourth day after surgery in combination with steroids, tacrolimus, and mycophenolic acid. Within the 10th postoperative day, steroids were progressively withdrawn. He had a delayed graft function that, however, resolved within 1 month, ending in a good graft function (creatinine 1.5 mg/ dL, estimated glomerular filtration rate 53 mL/min/1.73 m2 at 30th postoperative day). During the follow-up, prostate specific antigen (PSA) was constantly monitored and was undetectable until 31 months after KT; 2 years after the transplant, he presented in good clinical status with a good graft function, but his serum PSA level was increased to 5.1 ng/mL. The case was discussed in a multidisciplinary meeting between transplant surgeons, urologists, radiologists, and oncologists in order to decide the therapeutic approach. A choline-positron emission tomography/computed tomography (PET/CT) total body was performed, showing an increased uptake in a right pararectal obturator lymph node (23 mm diameter), diagnostic for PCa recurrence. At this time, patient immunosuppressive therapy was tacrolimus (2.5 mg once a day of prolonged release formulation) and mycophenolic acid (360 mg twice a day). *Address correspondence to Daniele Sforza, MD, PhD, Department of Hepatobiliary Surgery and Transplant Unit, University of Rome “Tor Vergata,” Italy, Policlinico Tor Vergata, Viale Oxford, 81, 00133 Rome, Italy. Tel: 0039 0620901, Fax: 0039 06.2090.0018. E-mail: [email protected] 0041-1345/19 https://doi.org/10.1016/j.transproceed.2019.04.098
1
2 After the diagnosis of tumor recurrence, the dose of mycophenolic acid was reduced to 180 mg twice a day, and tacrolimus was switched to everolimus 0.5 mg twice a day. Targeted RT was started, at which time the serum PSA level was 7.63 ng/mL, creatinine 1.1. mg/dL, and estimated glomerular filtration rate 65 mL/min/1.73 m2. RT ended after 6 months: the serum PSA level was undetectable, and both choline-PET/CT total body and magnetic resonance results were negative for cancer recurrence. Four years after RT, the graft function remains stable, without signs of PCa recurrence.
MATERIALS AND METHODS Three different investigators (M.M., M.P., A.P.) searched, independently, in PubMed, Google Scholar, and Transplant Library for all the literature regarding prostate cancer recurrence in renal transplant recipients from 1990 since early 2018. Key words were “prostate cancer recurrence," “renal transplant recipients," “kidney transplant," “radiotherapy," “fluorocholine pet," and “prostate specific antigen.” A fourth investigator (D.S.) reviewed all the papers selected.
DISCUSSION
The true incidence of PCa in RTRs is difficult to determine because most transplant registry data were obtained before the existence of systematic screening for this disease [6]. PCa is the second most common cause of cancer death in the United States; it is highly age dependent and is most commonly diagnosed after the age of 50 (with the median age of diagnosis being 71 years). The PCa diagnoses will increase in male renal transplant patients with the increasing use of screening tests. The literature has no homogeneous series of RTRs with relatively high prevalence of PCa [7-9]. Although there is no solid evidence of higher incidence of PCa in RTRs, this may be a challenging event since there are no specific guidelines for treatment of these patients, whose prognosis is worsened. Many studies concluded that RTRs have a low but real risk of cancer recurrence and cancer-related death. Low-risk patients may be candidates for transplantation after 2 years without recurrence, while stage III disease patients should have at least a 5-year disease-free period before transplantation [10,11]. In nonimmunosuppressed patients, radiation and surgery are considered potentially curative in localized PCa with roughly equivalent cure rates at 10 years, but surgery may be associated with higher survival at 15 years. In the surgery setting of future KT, retropubic radical prostatectomy can complicate the placement of future renal transplant by causing extraperitoneal fibrosis, whereas the perineal approach preserves the bladder and both iliac fossa for further transplant [12]. Although RP could cause critical surgical problems during transplantation, it is associated with a shorter waiting list, and it ensures the best oncological prognosis both before and after kidney transplantation [10]. There is no uniform definition for “biochemical relapse;” generally, a patient who has undergone RP should have no remaining nonmalignant PSA-producing tissue. Both the American Urological Association and American Society of Radiation Oncology guidelines and the European
SFORZA, PARENTE, PELLICCIARO ET AL
Association of Urology guidelines describe biochemical postprostatectomy recurrence as a detectable or rising PSA value > 0.2 ng/mL with a second confirmation level > 0.2 ng/mL [13e16]. Evidence suggests that choline PET/CT can be helpful for the evaluation of locoregional and distant metastatic disease in men with increasing PSA level, increasing PSA velocity, and decreasing PSA doubling time [17]. In general, choline PET/CT has a low to modest sensitivity and a high specificity for detecting involved nodes in the pelvic region [14,15]. After detection of PCa relapse, it is critical to choose the correct therapy. RT has demonstrated to be helpful and well tolerated in RTRs [18]. It has been suggested that the pharmacologic therapy in RTRs, such as corticosteroids and immunosuppressive drugs, can further increase the risk of RT side effects. It is important that the dose delivered to the graft remains minimal, possibly below the threshold, to affect renal function. Furthermore, checking for a full bladder before irradiation in RTRs may provide a simple but effective means on reducing the risk of late side effects to the donor ureter [19]. CONCLUSIONS
An adequate oncologic follow-up is crucial in kidney transplanted patients with a history of PCa, even after several years of being disease free. Furthermore, we believe that a multidisciplinary approach is paramount in the management of PCa recurrence in the renal transplanted population. REFERENCES [1] Lilja H, Christensson A, Dahlen U, et al. Prostate-specific antigen in serum occurs predominantly in complex with alpha 1antichymotrypsin. Clin Chem. 1991;37:1618e1625. [2] Christensson A, Bjbrk T, Nilsson O, et al. Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J Urol. 1993;150:100e105. [3] Partin AW, Piantadosi S, Subong EN, et al. Clearance rate of serum-free and total PSA following radical retropubic prostatectomy. Prostate Suppl. 1996;7:35e39. [4] Keinclauss FM, Neuzillet Y, Tillou X, et al. Morbidity of retropubic radical prostatectomy for prostate cancer in renal transplant recipients: multicenter study from Renal Transplantation Committee of French Urological Association. Urology. 2008;72: 1366e1370. [5] Beauval JB, Roumiguié M, Filleron T, et al. Biochemical recurrence-free survival and pathological outcomes after radical prostatectomy for high-risk prostate cancer. BMC Urol. 2016;16:26. [6] Penn I. Post-transplant malignancy: the role of immunosuppression. Drug Saf. 2000;23:101e113. [7] Diller R, Gruber A, Wolters H, et al. Therapy and prognosis of tumors of the genitourinary tract after kidney transplantation. Transplant Proc. 2005;37:2089e2092. [8] Cormier L, Lechevallier E, Barrou B, et al. Diagnosis and treatment of prostate cancers in renal transplant recipients. Transplantation. 2003;75:237e239. [9] Malavaud B, Hoff M, Meidouge M, et al. PSA-based screening for prostate cancer after renal transplant. Transplantation. 2000;69:2461e2462. [10] Chahwan C, Doerfler A, Brichart N, et al. Prostate cancer before renal transplantation: a multicentre study. Progrès en urologie. 2017;27:166e175.
PROSTATE CANCER RECURRENCE [11] Tillou X, Chahwan C, Le Gal Sophie, et al. Prostatectomy for localized prostate cancer to prepare for renal transplantation in end-stage renal disease patients. Ann Transplant. 2014;19: 569e575. [12] Yiou R, Salomon L, Colombel M, et al. Perineal approach to radical prostatectomy in kidney transplant recipients with localized prostate cancer. Urology. 1999;53:822e824. [13] Evangelista L, Zattoni F, Rossi E. Early detection of prostate cancer relapse by biochemistry and diagnostic imaging. Q J Nucl Med Mol Imaging. 2015;59:359e373. [14] Thompson IM, Valicenti RK, Albertsen P, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline. J Urol. 2013;190:441e449.
3 [15] Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014;65:467e479. [16] Lilja H, Ulmert D, Vickers AJ. Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer. 2008;8:268e278. [17] Jadvar J. Molecular imaging of prostate cancer with PET. J Nucl Med. 2013;54:1685e1688. [18] Binsaleh S. Diagnosis and treatment of prostate cancer in renal-transplant recipients. Int Urol Nephrol. 2012;44:149e155. [19] Mouzin M, Bachaud JM, Kamar N, et al. Three-dimensional conformal radiotherapy for localized prostate cancer in kidney transplant recipients. Transplantation. 2004;78:1496e1500.