te: Consider Clinical Trials as treatment options for eligible patients. This Prostate Cancer treatment consensus algorithm is used as a framework for the application of individualized therapy for patients with prostate cancer at the MD Anderson Cancer Center. The faculty and members of the Genitourinary Center apply this general algorithm to individual patients accommodating patient preference and physician experience in the context of a specific knowledge of prostate cancer.
te: Consider Clinical Trials as treatment options for eligible patients. INITIAL DIAGNOSIS STAGING WORKUP PRESENTING CLINICAL STAGE Prostate biopsy,2 DRE PSA Gleason score Life expectancy greater than or equal to 5 years, or symptomatic from local or metastatic disease Life expectancy less than 5 years and asymptomatic Bone scan if: PSA greater than 5 ng/ml or ct3-ct4 disease or Bone pain or Positive nodes on CT/MRI imaging or Gleason scores of 8-0 or Adverse histologies (e.g. small cell and/or neuroendocrine) CT or MRI considered for high risk patients based on NCCN guidelines 3 FNA if clinically indicated cta ctb, ctc, ct2a, ct2b ct3a ct3b, ct4 Any TN, M0 See Page 3 of this algorithm See Page 4 of this algorithm Follow up annually, no further work up until symptoms, for example, bone pain or voiding dysfunction Symptomatic Perform prostate biopsy if not previously done. If done, MDACC review of prostate biopsy results. 2 Refer to Appendix A Approved MD Anderson Prostate Biomarkers on page 9. 3 http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf Any T or N, M Any N M with Visceral or lytic bone metastases and low PSA
te: Consider Clinical Trials as treatment options for eligible patients. PRESENTING CLINICAL STAGE ctb cta ctc, ct2a, ct2b Life expectancy less than 0 years Life expectancy greater than or equal to 0 years TRUS biopsy Life expectancy greater than or equal to 0 years? TRUS biopsy Low Risk Disease: ct-ct2a and PSA less than 0 ng/ml and Gleason score 2-6 Intermediate Risk Disease: ct2b (but not qualifying for high risk disease) or PSA 0-20 ng/ml or Gleason score 7 High Risk Disease: ct2c-ct3a or PSA greater than 20 ng/ml or Gleason score 8-0 INITIAL THERAPY Active suveillance External beam radiation 4 Brachytherapy 3 Radical prostatectomy 5 Cryotherapy 3,6 See Page 7 for appropriate active surveillance based on initial therapy Monitor patient for symptoms; consider treatment if progression or Consider external beam radiotherapy 2 or cryoablation or hormonal ablation (See Box A, Page 6) Refer to Appendix A Approved MD Anderson Prostate Biomarkers on page 9. 2 All localized treatments: length of follow-up and quality of data differ with each treatment and should be discussed with your treatment team. 3 Brachytherapy and cryotherapy eligibility limited by prostate size, pubic bone geometry, baseline urinary function. 4 External beam radiation should be dose escalated using either IMRT (intensity modulated radiation therapy), or proton therapy. Inflammatory bowel disease and peri-rectal disease may be contraindications. 5 Radical prostatectomy is performed by open retropubic or robot assisted technique. These technique choices, eligibility for a nerve sparing procedure, and the need for a pelvic lymph node dissection should be discussed with your treatment team. 6 External beam radiation and brachytherapy radical prostatectomy have longer duration of follow-up and may be preferred over cryotherapy. This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, TRUS biopsy if Gleason score 8-0 t reclassified to higher risk Reclassified to higher risk Locally Advanced See Page 4 Monitor patient for symptoms; consider treatment if progression Active surveillance or Consider external beam radiotherapy 2 or brachytherapy 3 Radical prostatectomy 2 if life expectancy greater than 20 years Consider treatment based on new stage Brachytherapy 3 (on protocol) Cryotherapy 6 External beam radiation with 4-6 months adjuvant androgen ablation (See Box A, Page 6) Radical prostatectomy Active surveillance (on protocol) Cryotherapy 6 External beam radiation with 2-3 years adjuvant androgen ablation (See Box A, Page 6) Radical prostatectomy See Page 7 for appropriate follow up or active surveillance based on initial therapy
te: Consider Clinical Trials as treatment options for eligible patients. PRESENTING CLINICAL STAGE INITIAL THERAPY FOLLOW-UP Locally Advanced (ct3a, ct3b, ct4) External beam radiotherapy with androgen ablation, 3 or Androgen ablation 3 (See Page 6, Box A) or Consider radical prostatectomy in selected cases or on protocol Any T N Life Expectancy greater than or equal to 5 years or symptomatic? Consider 6-2 months androgen ablation Favorable clinical response Consider androgen ablation 3 (See Page 5 or 6) Consider: Radiotherapy or Consider radical prostatectomy or Clinical trial PSA every 3 months, Radiographic studies if clinically indicated (bone scans, CT of abdomen and pelvis) Any T or N M Androgen ablation 3 (See Page 5 or 6) Any N, M with visceral or lytic bone metastases and low PSA Biopsy 4 metastatic lesions Pathology shows Small Cell component and/or neuroendocrine markers Cisplatin and Etoposide or Clinical Trial or Palliative Care 3D conformal radiotherapy or intensity modulated radiotherapy (IMRT) are standard for external beam radiotherapy. 2 Based on pathologic findings after radical prostatectomy (e.g. path stage, margin status, Gleason score, age), consider adjuvant external beam radiotherapy. 3 Treatment recommendation is dependent of life expectancy. See Page 6. 4 Refer to Appendix A Approved MD Anderson Prostate Biomarkers on page 9.
te: Consider Clinical Trials as treatment options for eligible patients. ANDROGEN ABLATIVE THERAPY Intermittent androgen ablation FOLLOW-UP Follow up visit every 3 months with PSA and testosterone, repeat imaging if rising PSA and/or clinical progression, and liver function tests every month for 3 months if on antiandrogens. Rising PSA or other signs of progression? ANDROGEN-INDEPENDENT SALVAGE THERAPY If on anti-androgen alone, add LHRH agonist; if progression, go to Box C on page 6 If on LHRH agonist alone, switch to continuous androgen ablation and add anti-androgen; if progression, go to Box B on Page 6 Continue follow up and current treatment Progression High volume bone disease 4 Androgen ablative therapy with LHRH analogue plus docetaxel for 6 cycles For Continuous Androgen Ablation, see Box A on Page 6 Consider intermittent androgen ablation for rising PSA only. If skeletal metastases are present, recommend 7 to 4 days of anti-androgen prior to initiation of LHRH agonist to prevent flare. 2 Consider baseline bone density scan and bisphosphonate therapy every 6 months to minimize osteoporosis associated with LHRH agonist use. 3 Check liver function tests month after initiation of anti-androgen and then with each 3 month follow up visit thereafter. 4 Visceral metastasis and/or greater than or equal to 4 bone metastasis
A ANDROGEN ABLATIVE THERAPY Continuous androgen ablation with LHRH agonist alone, 2 or with anti-androgen 3 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, te: Consider Clinical Trials as treatment options for eligible patients. FOLLOW-UP Follow-up Return to clinic every 3 months: Routine labs, PSA, testosterone, and liver function tests. Repeat imaging if rising PSA and/or clinical progression. B Radiographic progression without symptoms of progression Rising PSA 4? ANDROGEN-INDEPENDENT SALVAGE THERAPY C Discontinue antiandrogen Decreasing PSA? Secondary hormone therapies or noncytotoxics Antiandrogen 3, Diethylstibestrol, Abiraterone, Enzalutamide, Sipuleucel-T, Ketoconazole, or low dose Glucorticoids Continue followup without imaging studies unless clinically indicated Radiographic progression with symptoms of progression? Chemotherapy (Docetaxel and Glucocorticoids) or Consider Xofigo Consider Clinical trial or Consider Supportive care Progression Progression without visceral or lytic bone metastases Secondary hormone therapies or noncytotoxics Anti-androgen 3, Diethylstilbestrol, Abiraterone, Enzalutamide, Sipuleucel-T, Ketoconazole, or Low-dose Glucocorticoids if not previously given or Clinical trial or Observation Biopsy metastatic lesion If skeletal metastases are present, recommend 7 to 4 days of antiandrogen prior to initiation of LHRH agonist to prevent flare. 2 Consider baseline bone density scan and bisphosphonate therapy every 6 months to minimize osteoporosis associated with LHRH agonist use. 3 Check Liver Function Tests month after initiation of antiandrogen and then with each 3 month follow up visit thereafter. 4 If testosterone greater than or equal to 50 on LHRH analogue, consider orchiectomy or GNRH receptor antagonist to achieve testosterone less than or equal to 49. 5 Appropriately elevated PSA corresponds to radiographic volume of disease related to PSA. 6 Cytoxan with Vincristine and Dexamethasone; Carboplatin with Taxane; KAVE. Progression with only or predominately visceral metastasis Progression with only or predominately lytic osteoblastic bone metastases Appropriately elevated PSA 5? 70a Clinical trial or Radio-isotopes such as Xofigo, Palliative radiotherapy or Strontium 89, Samarium 53 Cabazitaxel or Salvage chemotherapy 6 or Supportive care Secondary hormone therapies or noncytotoxics Anti-androgen 3, Enzalutamide, Diethylstilbestrol, Abiraterone, Sipuleucel-T, Ketoconazole, or low dose Glucorticoids if not previously given Pathology shows adenocarcinoma Pathology shows small cell component and/or neuroendocrine component Cisplatin and Etoposide or Carboplatin/Docetaxel Clinical Trial or Palliative Care
te: Consider Clinical Trials as treatment options for eligible patients. PATIENT STATUS Patient on active surveillance ACTIVE SURVEILLANCE Consider active surveillance protocol PSA and DRE every 6 months TRUS biopsy at baseline and annually (option to skip years if -2 negative biopsies in a row) Consider active surveillance support group Consider MRI pelvis with endo-rectal coil or targeted MRI/US fusion biopsy of suspicious lesion(s) FOLLOW UP (Continue monitoring until progression) PROGRESSION PSA trend and/or repeat biopsy indicates reclassification to higher risk, or symptomatic, or unable to tolerate further biopsies Refer to appropriate stage on Pages 3 or 4 of this guideline Patient post definitive therapy (i.e. radiotherapy or radical prostatectomy) Symptom evalation -PSA every 3-6 months for 5 years, then every 6-2 months for 5 years, then annually After radiotherapy: -DRE every 6-2 months After radical prostatectomy: -DRE every -3 years with follow-up visit Signs of recurrence or progression? Patient 5 or more years from treatment? See Page 8 for Recurrent Prostate Cancer Transfer to Survivorship Clinic Status post radical prostatectomy with positive surgical margins and/or pt3a or b, and Nx/N0, PSA undetectable after surgery Consider randomized clinical trials supporting the long-term survival benefits of adjuvant radiation weighed against the side effects, continue monitoring
(Recurrence) This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, te: Consider Clinical Trials as treatment options for eligible patients. PROGRESSION SALVAGE THERAPY Patient presents after surgery or radiation with positive DRE or increasing PSA Post- Radiotherapy Post-radical Prostatectomy Bone scan, abdominal and pelvic CT Bone scan and CT scans positive? Bone scan, abdominal and pelvic CT, MRI pelvis with endo-rectal coil, TRUS Consider prostate bed biopsy Consider Prostascint scan with co-registration Androgen ablation (See Page 5 for intermittent or Page 6 for continuous) Consider prostate biopsy Bone scan and CT scans positive? Biopsy positive? or not done Androgen ablation (See Page 5 for intermittent or Page 6 for continuous) Observation External beam radiotherapy 2 or Androgen ablation Consider prostatectomy or Cyoablation or Radio-isotopic implant Androgen ablation Observation Observation Androgen ablation Rising PSA after radical prostatectomy is greater than 0.2 ng/ml Rising PSA after radiotherapy or brachytherapy PSA is greater than 2.0 ng/ml above the nadir (lowest value post treatment off androgen deprivation, or medical castration therapy [ADT]) 2 Numerous studies indicate that salvage external beam radiotherapy is most effective if delivered with a PSA less than 0.5 ng/ml
te: Consider Clinical Trials as treatment options for eligible patients. APPENDIX A: Prostate Cancer Molecular Markers MD ANDERSON APPROVED DISEASE SITE BIOMARKER CELL TYPE FISH IMMUNOHISTOCHEMISTRY MOLECULAR GU Prostate PSA PAP CgA Literature support for MD Anderson approved Biomarkers is available and can be found under Clinical Management Algorithms Biomarkers MD Anderson Approved Literature support for MD Anderson approved Biomarkers is available and can be found under Clinical Management Algorithms Biomarkers MD Anderson Approved Approved by the Executive Committee Department of the of Medical Clinical Staff Effectiveness 0/28/204 V0
te: Consider Clinical Trials as treatment options for eligible patients. SUGGESTED READINGS Abuzallouf S, Dayes I, Lukka H, et al. (2004).Baseline staging of newly diagnosed prostate Cancer: a summary of the literature. Journal of Urology. 7(6 Pt ):22-7. Bolla M, Collette L, Blank L, et al. (2002). 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, 360:0306. Bolla M, van Poppel H, Collette L, et al. (2005). European Organization for Research and Treatment of Cancer. Postoperative radiotherapy after radical prostatectomy: A randomized controlled trial (EORTC trial 229). Lancet, 366:572 8. Chin JL, Pautler SE, Mouraviev V, et al. (200). Results of salvage cryoablation of the prostate after radiation: Identifying predictors of treatment failure and complications. Journal of Urology, 65:937-942. D'Amico AV, Manola J, Loffredo M, et al. (2004). 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA, 292(7):82-827. De La Taille A, Benson MC; Bagiella E, et al. (2000). Cryoablation for clinically localized prostate cancer using an argon-based system: complication rates and biochemical recurrence. BJU International, 85:28-286. Papandreou CN., Daliani DD, Thall PF, et al. (2002). Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate. Journal of Clinical Oncology, 20: 3072-3080. Petrylak DP, Tangen CM, Hussain MHA, et al. (2004). Docetaxel and Estramustine Compared with Mitoxantrone and Prednisone for Advanced Refractory Prostate Cancer. NEJM, 35:53-520. Pollack A, Zagars GK, Antolak, JA, et al. (2002). Prostate biopsy status and PSA nadir level as early surrogates for treatment failure: analysis of a prostate cancer randomized radiation dose escalation trial. International Journal of Radiation Oncology, Biology, Physics, 54:677-685. Pound CR, Partin AW, Eisenberger MA, et al. (999). Natural history of progression after PSA elevation following radical prostatectomy. JAMA, 28: 59-597. Stephenson AJ, Shariat SF, Zelefsky MJ, et al. (2000). Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. JAMA, 29:325-332. Tannock IF, de Wit RB, Berry WR, et al. (2004). Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. NEJM, 35:502-52. TNM Staging, 6th Edition, Copyright 2004 by John Wiley & Sons, Inc. Thompson IM Jr, Tangen CM, Paradelo J, et al. (2006). Adjuvant radiotherapy for pathologically advanced prostate cancer: A randomized clinical trial. JAMA, 296:2329 35. Wiegel T, Bottke D, Steiner U, et al. (2009). 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, 27: 2924-30.
te: Consider Clinical Trials as treatment options for eligible patients. DEVELOPMENT CREDITS This practice consensus algorithm is based on majority expert opinion of the GU Center Faculty at the University of Texas, MD Anderson Cancer Center. It was developed using a multidisciplinary approach that included input from the following medical oncologists, radiation oncologist, and urologic oncologists: Ana Aparicia, MD John Araujo, MD Seungtaek Choi, MD Paul Corn, MD, PhD John W. Davis, MD Colin P Dinney, MD Steven Frank, MD Ashish Kamat, MD Jeri Kim, MD Deborah A Kuban, MD Andrew K. Lee, MD, MPH Christopher J Logothetis, MD Surena Matin, MD Lance C Pagliaro, MD Curtis A Pettaway, MD Louis L Pisters, MD Shi-Ming Tu, MD John F. Ward, MD Amado Zurita-Saavedra, MD Core Development Team