|Year : 2014 | Volume
| Issue : 4 | Page : 278-285
Saudi oncology society and Saudi urology association combined clinical management guidelines for prostate cancer
Sultan Alkhateeb1, Ashraf Abusamra2, Danny Rabah3, Mohammed Alotaibi4, Rana Mahmood5, Mubarak Almansour6, Esam Murshid7, Abdullah Alsharm8, Ashwaq Alolayan9, Imran Ahmad10, Hussain Alkushi6, Abdullah Alghamdi11, Shouki Bazarbashi12
1 Department of Surgery, Division of Urology, King Abdulaziz Medical City-Riyadh, Saudi Arabia
2 Section of Urology, Department of Surgery, King Khaled Hospital, King Abdulaziz Medical City-Jeddah, Saudi Arabia
3 Department of Surgery, Division of Urology, College of Medicine, King Khalid University Hospital; Princess Al Johora Al-Ibrahim Centre for Cancer Research (Uro-Oncology Research Chair), King Saud University, Riyadh, Saudi Arabia
4 Department of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
5 Section of Radiation Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
6 Oncology department, Princess Noura Oncology Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia
7 Department of Oncology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
8 Department of Oncology, King Fahad Medical City, Riyadh, Saudi Arabia
9 Department of Oncology, King Abdulaziz Medical City-Riyadh, Saudi Arabia
10 Department of Oncology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
11 Department of Urology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
12 Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
|Date of Submission||15-Apr-2014|
|Date of Acceptance||15-Apr-2014|
|Date of Web Publication||18-Sep-2014|
Department of Surgery, Division of Urology, College of Medicine King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, Princess Al-Johora Al-Ibrahim Centre for Cancer Research (Uro-Oncology Research Chair), King Saud University, Riyadh
| Abstract|| |
In this report, updated guidelines for the evaluation, medical, and surgical management of prostate cancer are presented. They are categorized according the stage of the disease using the tumor node metastasis staging system 7 th edition. The recommendations are presented with supporting evidence level.
Keywords: Cancer, guidelines, management, prostate, Saudi
|How to cite this article:|
Alkhateeb S, Abusamra A, Rabah D, Alotaibi M, Mahmood R, Almansour M, Murshid E, Alsharm A, Alolayan A, Ahmad I, Alkushi H, Alghamdi A, Bazarbashi S. Saudi oncology society and Saudi urology association combined clinical management guidelines for prostate cancer. Urol Ann 2014;6:278-85
|How to cite this URL:|
Alkhateeb S, Abusamra A, Rabah D, Alotaibi M, Mahmood R, Almansour M, Murshid E, Alsharm A, Alolayan A, Ahmad I, Alkushi H, Alghamdi A, Bazarbashi S. Saudi oncology society and Saudi urology association combined clinical management guidelines for prostate cancer. Urol Ann [serial online] 2014 [cited 2020 Jan 20];6:278-85. Available from: http://www.urologyannals.com/text.asp?2014/6/4/278/140959
| Manuscript|| |
In Saudi Arabia, prostate cancer is the 6 th most common cancer among men of all ages and the most common cancer among men over the age of 75. It accounts for 6.1% of all newly diagnosed cases among males in year 2010 with an age-standardized incidence rate of 5.5/100,000 among the male population. Stage at the time of diagnosis is localized in 43.9% of cases with the remainder being either locally advanced, metastatic or unknown. 
1. STAGING EVALUATION
Once diagnosis is confirmed, the following staging evaluation should be done:
1.1. Computed tomography (CT) or magnetic resonance imaging (MRI) abdomen and pelvis: Should only be done when the cancer is considered high-risk [Table 1] (EL-2). ,
1.2. Bone scan: Should only be done if any of the following (EL-2): ,
1.2.1. Prostate-specific antigen (PSA) level > 20 ng/mL.
1.2.2. Patients with bony pain.
1.2.3. Gleason score >7.
1.2.4. Patient with clinical stage T3 or T4.
1.2.5. Hypercalcemia, high serum alkaline phosphatase.
2. STAGING CLASSIFICATION
The tumor node metastasis staging will be used 
Primary tumor (T)
TX - Tumor cannot be assessed
T0 - No evidence of the primary tumor
T1 - Clinically neither palpable nor visible by imaging
T1a - Found incidental to other surgery; present in 5% or less of tissue
T1b - Found incidental to other surgery; present in 5% or more of tissue
T1c - Identified by needle biopsy
T2 - Tumor confined within prostate
T2a - Involving one-half of one lobe or less
T2b - Involving more than one-half of one lobe, but not both lobes
T2c - Involving both lobes
T3 - Tumor extends through prostate capsule
T3a - Extracapsular extension (unilateral or bilateral)
T3b - Tumor invades the seminal vesicle (s)
T4 - Involves structures other than seminal vesicles
T4a - Invades adjacent structure (s) other than seminal vesicles: Bladder, external sphincter, or rectum, lavatory muscle and (or) pelvic side walls
T4b - Invades muscles and/or pelvic wall
Regional lymph nodes (N)
NX - Nodes cannot be assessed
N0 - No regional node metastasis
N1 - Metastasis in regional nodes
Distant Metastasis (M)
M0 - No distant metastasis
M1 - Distant metastasis
M1a - Nonregional lymph node (s)
M1b - Bone (s)
M1c - Other site (s) with or without bone disease
3. MANAGEMENT OPTIONS
This will depend on the stage (localized vs. metastatic), the risk group and life expectancy. 
3.1. Localized disease (cT1-cT2)
3.1.1. Low risk: Options of therapy depend on the following factors:
22.214.171.124. If the patient is asymptomatic with life expectancy <5 years: No further intervention required until he becomes symptomatic or clinical progression ,, (EL-2).
126.96.36.199. If asymptomatic with life expectancy between 5 and 10 years: Active surveillance (involves active monitoring of the course of disease with the expectation to intervene with curative intent if the cancer progresses) ,, (EL-2).
188.8.131.52. If asymptomatic with life expectancy >10 years: Options include active surveillance,  radical prostatectomy (RP),  external beam radiation therapy (EBRT),  or brachytherapy  (EL-2).
184.108.40.206. The choice of therapy should depend on the patient's general condition, his preference and side-effect profile.
220.127.116.11. Active surveillance candidates must have all the following criteria: Number of positive cores ≤2, percentage of cancer involvement in any positive core <15%, PSA < 10, PSA density <0.15 and Gleason sum ≤6. Follow-up should entitle history, physical exam and PSA every 3-6 months, and repeated biopsy every 12-18 months; radical therapy should be offered if PSA velocity >0.35 ng/mL/year or progression in any of the aforementioned criteria. ,
18.104.22.168. All RPs should be done in tertiary care centers by high-volume surgeons  (EL-2).
22.214.171.124. Lymphadenectomy can be omitted if the chance of being positive is <5%  (EL-2).
126.96.36.199. Intensity-modulated EBRT is the minimal standard of EBRT, in which the only acceptable biological dose is ≥74 Gy ,,,,, (EL-2).
3.1.2. Intermediate risk: Options of therapy depend on the following factors:
188.8.131.52. If life expectancy is < 5 years: Patient will have no further intervention until he becomes symptomatic or clinical progression ,, (EL-2).
184.108.40.206. If life expectancy is between 5 and 10 years: Options include active surveillance,  EBRT with 6 months of androgen deprivation therapy (ADT), ,, or RP  (EL-2).
220.127.116.11. If life expectancy is more than 10 years: Options are RP with extended lymphadenectomy , (EL-1) or EBRT + 6 months of ADT ,,, (EL-2).
3.1.3. High-risk: Options include EBRT (to include pelvic lymph nodes) with 18-36 months of ADT. ,,,,,, (EL-1) or RP with extended lymphadenectomy , (EL-3). Patients who have advanced local disease and are unfit for the above mentioned two options may be given ADT alone (when PSA level exceeds 10 ng/mL)  (EL-1).
3.1.4. Follow-up after curative therapy: Patients should have a disease-specific history, serum PSA and digital rectal examination at 3, 6, and 12 months after therapy, then every 6 months for 3 years and then annually  (EL-3).
18.104.22.168. Patients who have pT3 with undetectable PSA, may undergo adjuvant EBRT to the prostatic bed (64-66 Gy) ,,,, (EL-2).
22.214.171.124. Patients who have positive (not focal) surgical margins may undergo adjuvant EBRT to the prostatic bed, , or intensive expectant follow-up , (EL-2).
3.1.5. Management of recurrence post RP:
126.96.36.199. Definition: Recurrence post-RP is defined by PSA level >0.2 ng/mL in two consecutive readings. ,
188.8.131.52. Factors helping to differentiate local relapse or distant metastasis are: The timing of PSA increase after surgery, PSA doubling time (PSADT), and the pathological stage and final Gleason score. ,,,,,,,
184.108.40.206. Treatment of local recurrence is salvage EBRT; for treatment of metastatic disease see 3.2.
220.127.116.11.1. Bone scan and CT scan are of no diagnostic value unless PSA value is higher than 20 ng/dl, ,, Gleason >7, or clinically indicated (EL-2).
3.1.6. Management of local recurrence after EBRT
18.104.22.168. Definition: A PSA rise 2 ng/mL above the PSA nadir is the most reliable indication for recurrence , (EL-2). However, local recurrence is defined by the presence of all of the following: , A prostatic biopsy showing malignant cells 18 months or longer after EBRT, associated rise in PSA, and no evidence of distant metastasis documented by CT scan or MRI and bone scan.
22.214.171.124. Options of therapy include: Observation up to PSA of 10 ng/dl, then ADT,  or in carefully selected patients, salvage prostatectomy, or brachytherapy may be considered. ,,,
3.2. Advanced disease (including recurrence and metastasis)
3.2.1. Hormone responsive disease:
126.96.36.199. ADT palliates symptoms and reduces the risk for potentially catastrophic sequelae of advanced disease (spinal cord compression, pathological fractures, ureteral obstruction, and extraskeletal metastasis) ,, (EL-1).
188.8.131.52. Options of ADT include: Orchiectomy, luteinizing hormone releasing hormone (LHRH) antagonist, LHRH agonists, and complete androgen blockade (CAB) continuous or intermittent. ,,
184.108.40.206. When treating with LHRH agonists a concomitant anti-androgen during the initial 4 weeks, to counteract the testosterone surge, must be given; also, it should be preceded with 10 days of antiandrogen in patients with significant disease burden.
220.127.116.11. All patients receiving ADT must be prescribed vitamin D and calcium supplements. 
18.104.22.168. High-risk patients with short PSADT, high initial PSA and symptomatic patients should preferably receive combined androgen blockade ,,,,,, (EL-2).
22.214.171.124. Castrate level of testosterone should be <20 ng/dl (0.7 nmol/L). ,
126.96.36.199. In case of intermittent androgen blockade (EL-2), the following should be observed: ,,,,
188.8.131.52.1. LHRH antagonist or CAB (antiandrogen and LHRH) should be used.
184.108.40.206.2. Initial induction cycle should last 6-9 months.
220.127.116.11.3. Treatment is usually stopped only if the patient is compliant, showing good PSA response with PSA <4 ng/dl in patients with metastatic disease and <0.5 ng/dl in recurrent disease post local therapy.
18.104.22.168.4 Therapy is re-instituted for 3-6 months cycle if PSA reaches 10-15 ng/dl in metastatic disease or 4 ng/dl in recurrent disease post local therapy.
22.214.171.124. In general, use of steroidal anti-androgens should be discouraged.
3.2.2. Castrate resistant prostate cancer (CRPC):
126.96.36.199. Definition: Two consecutive rises in PSA in the presence of castrate testosterone level.
188.8.131.52. Therapy should depend on the presence or absence of metastases.
184.108.40.206.1. In nonmetastatic CRPC treatment secondary hormonal manipulations may be offered by either adding a nonsteroidal anti-androgen, anti -androgen withdrawal, ketoconazole, steroids, diethylstilbestrol, or other estrogens. ,,,,,
220.127.116.11.2. In asymptomatic metastatic CRPC treatment options include abiraterone with prednisone, systemic chemotherapy, or secondary hormonal manipulations (adding a nonsteroidal antiandrogen, or antiandrogen withdrawal). ,,,,
18.104.22.168.3. In symptomatic metastatic CRPC treatment options include abiraterone with prednisone (only in mildly symptomatic patients) or systemic chemotherapy. ,,,,
22.214.171.124.4. Systemic chemotherapy in the form of docetaxel with prednisone should be offered only to patients with performance status 0-2 by Eastern Cooperative Oncology Group scale. ,, (EL-1) The decision when to start chemotherapy should depend on factors like PSADT and presence of symptoms.
126.96.36.199.5. Patients who fail abiraterone may receive docetaxel with prednisone.
188.8.131.52.6. Patients who fail docetaxel, have several options of therapy including: Cabazitaxel with prednisone, abiraterone acetate (if not received in chemo-naive setting), and enzalutamide. ,,,
184.108.40.206.7. Patients who fail docetaxel and have disease limited to the bone can also be offered in addition to (220.127.116.11.6) alpharadin (Radium 223) where available. 
18.104.22.168.8. Patients with CRPC who were on LHRH antagonist/agonists should continue on them indefinitely ,, (EL-3).
22.214.171.124.9. Patients with bony metastatic CRPC should receive rank-ligand antibodies (Denosumab) therapy every 4 weeks (EL-1), but when not available zoledronic acid can be given (EL-1). ,,,,,
| References|| |
|1.||Saudi Cancer Registry Annual Report, 2010. Available from: http://www.scr.org.sa. Accessed 17 May 2014 |
|2.||Makarov DV, Trock BJ, Humphreys EB, Mangold LA, Walsh PC, Epstein JI, et al. Updated nomogram to predict pathologic stage of prostate cancer given prostate-specific antigen level, clinical stage, and biopsy Gleason score (Partin tables) based on cases from 2000 to 2005. Urology 2007;69:1095-101. |
|3.||Hövels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: A meta-analysis. Clin Radiol 2008;63:387-95. |
|4.||Kemp PM, Maguire GA, Bird NJ. Which patients with prostatic carcinoma require a staging bone scan? Br J Urol 1997;79:611-4. |
|5.||Lee N, Fawaaz R, Olsson CA, Benson MC, Petrylak DP, Schiff PB, et al. Which patients with newly diagnosed prostate cancer need a radionuclide bone scan? An analysis based on 631 patients. Int J Radiat Oncol Biol Phys 2000;48:1443-6. |
|6.||Edge SB, Byrd DR, Comton CC, Fritz, A.G., Greene, F.L., Trotti, A.(Eds). AJCC Cancer Staging Manual. 7 th ed. New York: Springer-Verlag; 2010. |
|7.||D′Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998;280:969-74. |
|8.||Chodak GW, Thisted RA, Gerber GS, Johansson JE, Adolfsson J, Jones GW, et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med 1994;330:242-8. |
|9.||Albertsen PC, Hanley JA, Gleason DF, Barry MJ. Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer. JAMA 1998;280:975-80. |
|10.||Klotz L. Active surveillance for prostate cancer: For whom? J Clin Oncol 2005;23:8165-9. |
|11.||Bill-Axelson A, Holmberg L, Ruutu M, Häggman M, Andersson SO, Bratell S, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005;352:1977-84. |
|12.||Kupelian P, Kuban D, Thames H, Levy L, Horwitz E, Martinez A, et al. Improved biochemical relapse-free survival with increased external radiation doses in patients with localized prostate cancer: The combined experience of nine institutions in patients treated in 1994 and 1995. Int J Radiat Oncol Biol Phys 2005;61:415-9. |
|13.||Potters L, Morgenstern C, Calugaru E, Fearn P, Jassal A, Presser J, et al. 12-year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urol 2008;179:S20-4. |
|14.||Klotz L, Zhang L, Lam A, Nam R, Mamedov A, Loblaw A. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010;28:126-31. |
|15.||Tosoian JJ, Trock BJ, Landis P, Feng Z, Epstein JI, Partin AW, et al. Active surveillance program for prostate cancer: An update of the Johns Hopkins experience. J Clin Oncol 2011;29:2185-90. |
|16.||Eastham JA, Kattan MW, Riedel E, Begg CB, Wheeler TM, Gerigk C, et al. Variations among individual surgeons in the rate of positive surgical margins in radical prostatectomy specimens. J Urol 2003;170:2292-5. |
|17.||Cagiannos I, Karakiewicz P, Eastham JA, Ohori M, Rabbani F, Gerigk C, et al. A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer. J Urol 2003;170:1798-803. |
|18.||Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, et al. Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 2008;70:67-74. |
|19.||Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams JA, et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: A randomized controlled trial. JAMA 2005;294:1233-9. |
|20.||Zelefsky MJ, Leibel SA, Gaudin PB, Kutcher GJ, Fleshner NE, Venkatramen ES, et al. Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 1998;41:491-500. |
|21.||Zelefsky MJ, Chan H, Hunt M, Yamada Y, Shippy AM, Amols H. Long-term outcome of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer. J Urol 2006;176:1415-9. |
|22.||Chung P, Haycocks T, Panzarella T, Warde PR, Gospodarowicz MK, Milosevic M, et al. Results of escalated dose 3D conformal radiotherapy for intermediate risk prostate cancer- biochemical response and local control. Radiother Oncol 2002;64 (1): S120 |
|23.||D′Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: A randomized trial. JAMA 2008;299:289-95. |
|24.||Heidenreich A, Ohlmann CH, Polyakov S. Anatomical extent of pelvic lymphadenectomy in patients undergoing radical prostatectomy. Eur Urol 2007;52:29-37. |
|25.||Pollack A, Zagars GK, Smith LG, Lee JJ, von Eschenbach AC, Antolak JA, et al. Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J Clin Oncol 2000;18:3904-11. |
|26.||Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, et al. Prostate cancer radiation dose response: Results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 2002;53:1097-105. |
|27.||Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): A phase III randomised trial. Lancet 2002;360:103-6. |
|28.||Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 1997;337:295-300. |
|29.||Pilepich MV, Winter K, John MJ, Mesic JB, Sause W, Rubin P, et al. Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys 2001;50:1243-52. |
|30.||Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Movsas B, et al. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma - Long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys 2005;61:1285-90. |
|31.||Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H, Venkatesan V, et al. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: The Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol 2003;21:3972-8. Erratum in: J Clin Oncol 2004;22:386. |
|32.||Yossepowitch O, Eggener SE, Bianco FJ Jr, Carver BS, Serio A, Scardino PT, et al. Radical prostatectomy for clinically localized, high risk prostate cancer: Critical analysis of risk assessment methods. J Urol 2007;178:493-9. |
|33.||Lau WK, Bergstralh EJ, Blute ML, Slezak JM, Zincke H. Radical prostatectomy for pathological Gleason 8 or greater prostate cancer: Influence of concomitant pathological variables. J Urol 2002;167:117-22. Erratum in: J Urol 2004;171(2 Pt 1):811. |
|34.||Studer UE, Whelan P, Albrecht W, Casselman J, de Reijke T, Hauri D, et al. Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891. J Clin Oncol 2006;24:1868-76. |
|35.||Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281:1591-7. |
|36.||Bolla M, van Poppel H, Collette L, van Cangh P, Vekemans K, Da Pozzo L, et al. Postoperative radiotherapy after radical prostatectomy: A randomised controlled trial (EORTC trial 22911). Lancet 2005;366:572-8. |
|37.||Van der Kwast TH, Bolla M, Van Poppel H, Van Cangh P, Vekemans K, Da Pozzo L, et al. Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911. J Clin Oncol 2007;25:4178-86. |
|38.||Wiegel T, Bottke D, Steiner U, Siegmann A, Golz R, Störkel S, et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol 2009;27:2924-30. |
|39.||Swanson GP, Thompson IM, Tangen C, Paradelo J, Cany-Hagino E, Crawford ED, et al. Update of SWOG 8794: Adjuvant radiotherapy for pT3 prostate cancer improves metastasis free survival. Int J Rad Oncol Biol Phys 2008;72:S31. |
|40.||Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: Long-term followup of a randomized clinical trial. J Urol 2009;181:956-62. |
|41.||Stephenson AJ, Scardino PT, Kattan MW, Pisansky TM, Slawin KM, Klein EA, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol 2007;25:2035-41. |
|42.||Wiegel T, Lohm G, Bottke D, Höcht S, Miller K, Siegmann A, et al. Achieving an undetectable PSA after radiotherapy for biochemical progression after radical prostatectomy is an independent predictor of biochemical outcome - Results of a retrospective study. Int J Radiat Oncol Biol Phys 2009;73:1009-16. |
|43.||Boccon-Gibod L, Djavan WB, Hammerer P, Hoeltl W, Kattan MW, Prayer-Galetti T, et al. Management of prostate-specific antigen relapse in prostate cancer: A European Consensus. Int J Clin Pract 2004;58:382-90. |
|44.||Moul JW. Prostate specific antigen only progression of prostate cancer. J Urol 2000;163:1632-42. |
|45.||Partin AW, Pearson JD, Landis PK, Carter HB, Pound CR, Clemens JQ, et al. Evaluation of serum prostate-specific antigen velocity after radical prostatectomy to distinguish local recurrence from distant metastases. Urology 1994;43:649-59. |
|46.||Trapasso JG, deKernion JB, Smith RB, Dorey F. The incidence and significance of detectable levels of serum prostate specific antigen after radical prostatectomy. J Urol 1994;152:1821-5. |
|47.||Cheung R, Kamat AM, de Crevoisier R, Allen PK, Lee AK, Tucker SL, et al. Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy. Int J Radiat Oncol Biol Phys 2005;63:134-40. |
|48.||Lee AK, D′Amico AV. Utility of prostate-specific antigen kinetics in addition to clinical factors in the selection of patients for salvage local therapy. J Clin Oncol 2005;23:8192-7. |
|49.||Patel R, Lepor H, Thiel RP, Taneja SS. Prostate-specific antigen velocity accurately predicts response to salvage radiotherapy in men with biochemical relapse after radical prostatectomy. Urology 2005;65:942-6. |
|50.||Stephenson AJ, Shariat SF, Zelefsky MJ, Kattan MW, Butler EB, Teh BS, et al. Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. JAMA 2004;291:1325-32. |
|51.||Ward JF, Zincke H, Bergstralh EJ, Slezak JM, Blute ML. Prostate specific antigen doubling time subsequent to radical prostatectomy as a prognosticator of outcome following salvage radiotherapy. J Urol 2004;172:2244-8. |
|52.||Trock BJ, Han M, Freedland SJ, Humphreys EB, DeWeese TL, Partin AW, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA 2008;299:2760-9. |
|53.||Cher ML, Bianco FJ Jr, Lam JS, Davis LP, Grignon DJ, Sakr WA, et al. Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy. J Urol 1998;160:1387-91. |
|54.||Kane CJ, Amling CL, Johnstone PA, Pak N, Lance RS, Thrasher JB, et al. Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy. Urology 2003;61:607-11. |
|55.||Gomez P, Manoharan M, Kim SS, Soloway MS. Radionuclide bone scintigraphy in patients with biochemical recurrence after radical prostatectomy: When is it indicated? BJU Int 2004;94:299-302. |
|56.||Consensus statement: Guidelines for PSA following radiation therapy. American Society for Therapeutic Radiology and Oncology Consensus Panel. Int J Radiat Oncol Biol Phys 1997;37:1035-41. |
|57.||Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: Recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 2006;65:965-74. |
|58.||Cox JD, Gallagher MJ, Hammond EH, Kaplan RS, Schellhammer PF. Consensus statements on radiation therapy of prostate cancer: Guidelines for prostate re-biopsy after radiation and for radiation therapy with rising prostate-specific antigen levels after radical prostatectomy. American Society for Therapeutic Radiology and Oncology Consensus Panel. J Clin Oncol 1999;17:1155. |
|59.||Taylor JM, Griffith KA, Sandler HM. Definitions of biochemical failure in prostate cancer following radiation therapy. Int J Radiat Oncol Biol Phys 2001;50:1212-9. |
|60.||Pinover WH, Horwitz EM, Hanlon AL, Uzzo RG, Hanks GE. Validation of a treatment policy for patients with prostate specific antigen failure after three-dimensional conformal prostate radiation therapy. Cancer 2003;97:1127-33. |
|61.||Heidenreich A, Richter S, Thüer D, Pfister D. Prognostic parameters, complications, and oncologic and functional outcome of salvage radical prostatectomy for locally recurrent prostate cancer after 21st-century radiotherapy. Eur Urol 2010;57:437-43. |
|62.||Pisters LL, Rewcastle JC, Donnelly BJ, Lugnani FM, Katz AE, Jones JS. Salvage prostate cryoablation: Initial results from the cryo on-line data registry. J Urol 2008;180:559-63. |
|63.||Burri RJ, Stone NN, Unger P, Stock RG. Long-term outcome and toxicity of salvage brachytherapy for local failure after initial radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 2010;77:1338-44. |
|64.||Moman MR, van der Poel HG, Battermann JJ, Moerland MA, van Vulpen M. Treatment outcome and toxicity after salvage 125-I implantation for prostate cancer recurrences after primary 125-I implantation and external beam radiotherapy. Brachytherapy 2010;9:119-25. |
|65.||Seidenfeld J, Samson DJ, Hasselblad V, Aronson N, Albertsen PC, Bennett CL, et al. Single-therapy androgen suppression in men with advanced prostate cancer: A systematic review and meta-analysis. Ann Intern Med 2000;132:566-77. |
|66.||Samson DJ, Seidenfeld J, Schmitt B, Hasselblad V, Albertsen PC, Bennett CL, et al. Systematic review and meta-analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma. Cancer 2002;95:361-76. |
|67.||Iversen P, Tyrrell CJ, Kaisary AV, Anderson JB, Baert L, Tammela T, et al. Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: Results from two multicenter randomized trials at a median follow-up of 4 years. Urology 1998;51:389-96. |
|68.||National Osteoporosis Foundation. National Osteoporosis Foundation clinician′s guide to prevention and treatment of osteoporosis, 2013. Available from: http://www.nof.org/professionals/clinical-guidelines. [Last accessed on 2014 Mar 05]. |
|69.||Moul JW. Twenty years of controversy surrounding combined androgen blockade for advanced prostate cancer. Cancer 2009;115:3376-8. |
|70.||Seidenfeld J, Samson DJ, Aronson N, Albertson PC, Bayoumi AM, Bennett C, et al. Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer. Evidence Report/Technology Assessment No. 4. AHCPR Publication No. 99-E0012. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, US Department of Health and Human Services; 1999. |
|71.||Maximum androgen blockade in advanced prostate cancer: An overview of the randomised trials. Prostate Cancer Trialists′ Collaborative Group. Lancet 2000;355:1491-8. |
|72.||Schmitt B, Bennett C, Seidenfeld J, Samson D, Wilt T. Maximal androgen blockade for advanced prostate cancer. Cochrane Database Syst Rev 1999, Issue 2. Art. No.: CD001526. |
|73.||Schmitt B, Wilt TJ, Schellhammer PF, DeMasi V, Sartor O, Crawford ED, et al. Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: A systematic review. Urology 2001;57:727-32. |
|74.||Collette L, Studer UE, Schröder FH, Denis LJ, Sylvester RJ. Why phase III trials of maximal androgen blockade versus castration in M1 prostate cancer rarely show statistically significant differences. Prostate 2001;48:29-39. |
|75.||Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, et al. Combined androgen blockade with bicalutamide for advanced prostate cancer: Long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer 2009;115:3437-45. |
|76.||Oefelein MG, Feng A, Scolieri MJ, Ricchiutti D, Resnick MI. Reassessment of the definition of castrate levels of testosterone: Implications for clinical decision making. Urology 2000;56:1021-4. |
|77.||Oefelein MG, Cornum R. Failure to achieve castrate levels of testosterone during luteinizing hormone releasing hormone agonist therapy: The case for monitoring serum testosterone and a treatment decision algorithm. J Urol 2000;164:726-9. |
|78.||Abrahamsson PA. Potential benefits of intermittent androgen suppression therapy in the treatment of prostate cancer: A systematic review of the literature. Eur Urol 2010;57:49-59. |
|79.||Hussain M, Tangen CM, Higano C, Schelhammer PF, Faulkner J, Crawford ED, et al. Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: Data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol 2006;24:3984-90. |
|80.||Lane TM, Ansell W, Farrugia D, Wilson P, Williams G, Chinegwundoh F, et al. Long-term outcomes in patients with prostate cancer managed with intermittent androgen suppression. Urol Int 2004;73:117-22. |
|81.||Mottet N, Goussard M, Loulidi S, Wolff J. Intermittent versus continuous maximal androgen blockade in metastatic (D2) prostate cancer patients. A randomized trial. Eur Urol Suppl 2009;8:131. [Abstract 44]. |
|82.||Verhagen PC, Wissenburg LD, Wildhagen MF, Bolle WA, Verkerk AM, Schröder FH, et al. Quality of life effects of intermittent and continuous hormonal therapy by cyproterone acetate (CPA) for metastatic prostate cancer. Eur Urol Suppl 2008;7:206. [Abstract 541]. |
|83.||Tunn UW, Canepa G, Hillger H, Fuchs W. Intermittent androgen deprivation in patients with PSA relapse after radical prostatectomy-final results of a European randomized prospective phase-III clinical trial, AUO study AP 06/95, EC 507. American Urological Association; 2007. [Abstract 600]. |
|84.||de Leval J, Boca P, Yousef E, Nicolas H, Jeukenne M, Seidel L, et al. Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naive prostate cancer: Results of a prospective randomized multicenter trial. Clin Prostate Cancer 2002;1:163-71. |
|85.||Miller K, Steiner U, Lingnau A, Keilholz U, Witzsch U, Haider A, et al. Randomised prospective study of intermittent versus continuous androgen suppression in advanced prostate cancer. J Clin Oncol 2007;25(18):5015. |
|86.||Calais da Silva FE, Bono AV, Whelan P, Brausi M, Marques Queimadelos A, Martin JA, et al. Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: Results from a randomised phase 3 study of the South European Uroncological Group. Eur Urol 2009;55:1269-77. |
|87.||Irani J, Celhay O, Hubert J, Bladou F, Ragni E, Trape G, et al. Continuous versus six months a year maximal androgen blockade in the management of prostate cancer: A randomised study. Eur Urol 2008;54:382-91. |
|88.||Higano C, Shields A, Wood N, Brown J, Tangen C. Bone mineral density in patients with prostate cancer without bone metastases treated with intermittent androgen suppression. Urology 2004;64:1182-6. |
|89.||Cherrier MM, Aubin S, Higano CS. Cognitive and mood changes in men undergoing intermittent combined androgen blockade for non-metastatic prostate cancer. Psychooncology 2009;18:237-47. |
|90.||Shaw GL, Wilson P, Cuzick J, Prowse DM, Goldenberg SL, Spry NA, et al. International study into the use of intermittent hormone therapy in the treatment of carcinoma of the prostate: A meta-analysis of 1446 patients. BJU Int 2007;99:1056-65. |
|91.||Salonen AJ, Viitanen J, Lundstedt S, Ala-Opas M, Taari K, Tammela TL, et al. Finnish multicenter study comparing intermittent to continuous androgen deprivation for advanced prostate cancer: Interim analysis of prognostic markers affecting initial response to androgen deprivation. J Urol 2008;180:915-9. |
|92.||Boccon-Gibod L, Hammerer P, Madersbacher S, Mottet N, Prayer-Galetti T, Tunn U. The role of intermittent androgen deprivation in prostate cancer. BJU Int 2007;100:738-43. |
|93.||Small EJ, Vogelzang NJ. Second-line hormonal therapy for advanced prostate cancer: A shifting paradigm. J Clin Oncol 1997;15:382-8. |
|94.||Ryan CJ, Small EJ. Role of secondary hormonal therapy in the management of recurrent prostate cancer. Urology 2003;62 Suppl 1:87-94. |
|95.||Dupont A, Gomez JL, Cusan L, Koutsilieris M, Labrie F. Response to flutamide withdrawal in advanced prostate cancer in progression under combination therapy. J Urol 1993;150:908-13. |
|96.||Sartor AO, Tangen CM, Hussain MH, Eisenberger MA, Parab M, Fontana JA, et al. Antiandrogen withdrawal in castrate-refractory prostate cancer: A Southwest Oncology Group trial (SWOG 9426). Cancer 2008;112:2393-400. |
|97.||Small EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, Picus J, et al. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: A phase III trial (CALGB 9583). J Clin Oncol 2004;22:1025-33. |
|98.||Oh WK, Kantoff PW, Weinberg V, Jones G, Rini BI, Derynck MK, et al. Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. J Clin Oncol 2004;22:3705-12. |
|99.||Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013;368:138-48. |
|100.||Suzuki H, Okihara K, Miyake H, Fujisawa M, Miyoshi S, Matsumoto T, et al. Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade. J Urol 2008;180:921-7. |
|101.||Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351:1502-12. |
|102.||Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: Updated survival in the TAX 327 study. J Clin Oncol 2008;26:242-5. |
|103.||Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513-20. |
|104.||de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364:1995-2005. |
|105.||Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: Final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2012;13:983-92. |
|106.||Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367:1187-97. |
|107.||de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: A randomised open-label trial. Lancet 2010;376:1147-54. |
|108.||Parker C, Nilsson S, Heinrich D, Helle SI, O′Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213-23. |
|109.||Manni A, Bartholomew M, Caplan R, Boucher A, Santen R, Lipton A, et al. Androgen priming and chemotherapy in advanced prostate cancer: Evaluation of determinants of clinical outcome. J Clin Oncol 1988;6:1456-66. |
|110.||Taylor CD, Elson P, Trump DL. Importance of continued testicular suppression in hormone-refractory prostate cancer. J Clin Oncol 1993;11:2167-72. |
|111.||Hussain M, Wolf M, Marshall E, Crawford ED, Eisenberger M. Effects of continued androgen-deprivation therapy and other prognostic factors on response and survival in phase II chemotherapy trials for hormone-refractory prostate cancer: A Southwest Oncology Group report. J Clin Oncol 1994;12:1868-75. |
|112.||Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 2009;361:745-55. |
|113.||Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: Results of a phase 3, randomised, placebo-controlled trial. Lancet 2012;379:39-46. |
|114.||Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94:1458-68. |
|115.||Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004;96:879-82. |
|116.||Aapro M, Abrahamsson PA, Body JJ, Coleman RE, Colomer R, Costa L, et al. Guidance on the use of bisphosphonates in solid tumours: Recommendations of an international expert panel. Ann Oncol 2008;19:420-32. |
|117.||Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: A randomised, double-blind study. Lancet 2011;377:813-22. |