Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması

Önal, Cem; GÜRDALLI, Salih; ÖZYİĞİT, Gökhan; SARI, Sait; akyol, fadıl; YAPICI, Bülent

Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması

Gökhan ÖZYİĞİT, (Hacettepe Üniversitesi, Tıp Fakültesi, Radyasyon Onkolojisi Anabilim Dalı, Ankara, Türkiye)

Fadıl AKYOL, (Girilmedi)

Cem ÖNAL, (Girilmedi)

Sait SARI, (Girilmedi)

Salih GÜRDALLI, (Girilmedi)

Bülent YAPICI (Girilmedi)

Türk Hematoloji Onkoloji Dergisi

2 0

Yıl: 2003 Cilt: 13 Sayı: 4 Sayfa Aralığı: 177 - 189 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması

Öz:

Prospektif olarak planlanan bu çalışma protokolüne, AJCC 1997 evreleme sistemine göre Tl-T3b NO MÖ prostat adenokanseri tanısı almış hastalar alınmıştır. Ekstrakapsüler yayılım, PSA $qeg$ 10ng/dL, Gleason skorunun 7 ve üzeri olması yüksek risk kriteri olarak kabul edilmekte ve bu kriterlerden birini taşıyan hasta yüksek risk grubuna ayrılmıştır. Bu kriterlerden hiçbirini taşımayan düşük riskli hasta grubuna 12 hafta süresince Triptorelin Asetat 3.75 mg İM 4 haftada bir ve 2 haftada bir Siproterin Asetat 300 mg IM'den oluşan hormon tedavisi sonrası küratif radyoterapi uygulanırken, yüksek riskli hasta grubunda radyoterapi sonrası 24 hafta süresince hormon tedavisine devam edilmiştir. Radyoterapi, prostat ve seminal vezikülleri l cm. emniyet sınırı ile kapsayacak şekilde 3 boyutlu planlama yapıldıktan sonra 200 cGy günlük fraksiyonlarla yedi ayrı alandan toplam 70 Gy olacak şekilde verilmiştir. Bu çalışmada Ocak 1998 - Aralık 2000 tarihleri arasında radyoterapisi tamamlanmış olan 50 hastanın ön değerlendirme sonuçları verilmektedir. Hastaların yaşları 53-76 (medyan 68 yaş) arasında değişmektedir. Yirmi bir hasta (% 42) T2a, 7 hasta (% 14) T2b, 18 hasta (%36) T3a ve 4 hasta (%8) T3b evrelerindedir. 22 hastanın Gleason skoru 7 ve üzerindedir. Biyop-si öncesi PSA değerleri 3.4-76.Ing/mL (medyan 15 ng/mL) arasındadır. Bu kriterlere göre 10 hasta düşük risk grubuna, 40 hasta yüksek risk grubuna alınmıştır. Çalışmaya alınan hastaların izlem süresi medyan 36 ay'dır. Neoad-juvan hormonoterapi sonrası PSA değerleri 0.02-16.7ng/mL (medyan 1.05 ng/mL), radyoterapi sonrası ise 0.01-10 ng/mL (medyan 0.67 ng/mL) arasındadır. Transrektal ultrasonografi ile ölçülen prostat hacimleri hormonoterapi önce-si 15-105 cc (medyan 38 cc), radyoterapi öncesi 14.5-65 cc (medyan 28 cc) olarak bulundu. Protokole dahil edilen yüksek risk grubundaki 11 hastada ve düşük risk grubunda l hastada biyokimyasal relaps tespit edildi. Bu hastalardan altısında radyoterapi sonrası uzak metastazlar gelişti. Üç olgu uzak metastaz sonrası, 3 olgu ise hastalık dışı nedenlerle kaybedilmiştir. RTOG kriterlerine göre 22 grade 1,18 grade II, 7 grade III akut rektal, 22 grade 1,23 grade II ve 2 grade III akut üretral toksisite saptandı. Radyoterapi sonrası en az 6 ay takip edilen hastalarımızda ciddi bir geç toksisite saptanmamıştır. Tedavi süresince, PSA düşüşü ve prostat hacim azalması istatistiki olarak anlamlı bulunmuştur. Bu çalışmada erken ve geç toksisiteler kabul edilebilir düzeyde görünmektedir.

Anahtar Kelime: Triptorelin Prostata özgü antijen Radyoterapi Adenokarsinom Prostat neoplazmları Siproteron asetat Antineoplastik ajanlar, hormonal

Konular: Tıbbi Araştırmalar Deneysel Üroloji ve Nefroloji Onkoloji

Combined hormonotherapy and definitive radiation therapy in localized prostate adenocarcinoma

Öz:

In this prospective study, according to AJCC 1997 staging system Tl-T3b histologically proven prostate adenocarci-noma patients were treated. Extracapsular extension, PSA$qeg$ 10 ng/dL and gleason score 7 and above were considered as high risk criteria and in case one of them is positive, the patient considered in the high risk group, otherwise treated in low risk group. Low risk patients were administered neoadjuvant hormonotherapy with Triptorelin acetate 3.75 mg/month IM and siproterin acetate 300 mg/15 days IM for only 12 weeks and thereafter were given radiotherapy. In high risk patients, we continued on hormonotherapy for 24 weeks more after the termination of radiotherapy. A total dose of 70 Gy external radiotherapy with 200 cGy daily fraction doses was delivered. In this study the preliminary results of 50 patients who completed radiotherapy between January 1998 and December 2000 were given. The medi-an age was 68 years (range 53-76). Their stages were distributed as follows: 21 (42%) T2a, 7 (14%) T2b, 18 (36%) T3a and 4 (8%). Twenty two patients had a gleason score above 6. Their pre-biopsy PSA levels ranged between 3,4 and 76.1 ng/mL (median 15 ng/mL). According to our risk criterias 10 patients were in the low risk group. Median follow up was 36 months. PSA levels measured before the initiation of radiotherapy were 0.02-16.7 ng/mL (median 1.05 ng/mL). This change in PSA levels before and after hormonotherapy was statistically significant (p<0.001). Prostate volumes that were measured at the beginning of therapy ranged between 15-105 cc (median 38 cc) and before radiotherapy were between 14.5-65 cc (median 28 cc). This volume change was also significant (p<0.001). Twelve patients had biochemical failures. Consequently two of six developed distant metastasis. Three patients died of prostate cancer, while 3 patients died of other medical diseases. Twenty two grade 1,18 grade II and 7 grade III acute rectal toxicity; 22 grade I, 23 grade II, 2 grade III acute urethral toxicity were observed according to RTOG/EORTC toxicity criteria. No serious late toxicity was observed in our patients who completed 6 months of follow up after radiotherapy. Neoadjuvant hormonotherapy seems to be effective in decreasing PSA levels and prostate volumes. The acute and subacute toxicities of this protocol also seem to be feasible.

Anahtar Kelime: Adenocarcinoma Prostatic Neoplasms Cyproterone Acetate Antineoplastic Agents, Hormonal Triptorelin Prostate-Specific Antigen Radiotherapy

Konular: Tıbbi Araştırmalar Deneysel Üroloji ve Nefroloji Onkoloji

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Edwards BK, Howe HL, Ries LA, et al. Annual report to the nation on the status of cancer, 1973-1999, featuring implications of age and aging on U.S. cancer burden. Cancer 94:2766-2792,2002.
2. Wingo PA, Ries LA, Rosenberg HM, et al. Cancer incidence and mortality, 1973-1995: a report card for the U.S. Cancer 82:1197-1207,1998.
3. Bagshaw MA, Ray GR, Cox RS. Radiotherapy of prostatic carcinoma: long- or short-term efficacy (Stanford University experience). Urology 25:17-23,1985.
4. Bagshaw MA, Cox RS, Ray GR. Status of radiation treatment of prostate cancer at Stanford University. NCI Monogr:47-60,1988.
5. Hanks GE, Martz KL, Diamond JJ. The effect of dose on local control of prostate cancer. Int J Radiat Oncol Biol Phys 15:1299-1305,1988.
6. Leibel SA, Hanks GE, Kramer S. Patterns of care outcome studies: results of the national practice in adenocarcinoma of the prostate. Int J Radiat Oncol Biol Phys 10:401-409,1984.
7. Paulson DF, Lin GH, Hinshaw W, et al. Radical surgery versus radiotherapy for adenocarcinoma of the prostate. J Urol 128:502-504,1982.
8. Teh BS, Aguilar E, Aguilar L, et al. Late toxicity of a phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonotherapy in the treatment of prostate cancer. 45th Annual meeting of the American society for Therapeutic Radiology and Oncology. Salt Lake City, USA; 2003.
9. King CR, Lehmann J, Adler JR, et al. CyberKnife radiotherapy for localized prostate cancer: rationale and technical feasibility. Technol Cancer Res Treat 2:25-30,2003.
10. Zelefsky MJ, Fuks Z, Hunt M, et al. High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Phys 53:1111-1116,2002.
11. ICRU. Prescribing, recording, and reporting photon beam therapy. Washington, DC: ICRU: International Commission on Radiation Units and Measurements; 1993.
12. ICRU. International Commission on Radiation Units and Measurements Report #62: Prescribing, recording, and reporting photon beam therapy (Supplement to ICRU Report 50). Washington, DC; 1999.
13. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the Euopean Organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341-1346,1995.
14. Consensus statement: guidelines for PSA following radiation therapy. American Society for Therapeutic Radiology and Oncology Consensus Panel. Int J Radiat Oncol Biol Phys 37:1035- 1041,1997.
15. D'Amico AV, Whittington R, Malkowicz SB, et al. A multivariate analysis of clinical and pathological factors that predict for prostate specific antigen failure after radical prostatectomy for prostate cancer. J Urol 154:131-138,1995.
16. Ritter MA, Messing EM, Shanahan TG, et al. Prostate-specific antigen as a predictor of radiotherapy response and patterns of failure in localized prostate cancer. J Clin Oncol 10:1208- 1217,1992.
17. Critz FA, Levinson K, Williams WH, et al. Prostate-specific antigen nadir of 0.5 ng/ml or less defines disease freedom for surgically staged men irradiated for prostate cancer. Urology 49:668-672,1997.
18. Schellhammer PF, el-Mahdi AM, Kuban DA, et al. Prostate-specific antigen after radiation therapy. Prognosis by pretreatment level and posttreatment nadir. Urol Clin North Am 24:407- 414,1997.
19. Keyser D, Kupelian PA, Zippe CD, et al. Stage T1-2 prostate cancer with pretreatment prostate specific antigen level _____ or = 10 ng/ml: radiation therapy or surgery? Int J Radiat Oncol Biol Phys 38:723-729,1997.
20. Pollack A, Zagars GK, Antolak JA, et al. Prostate biopsy status and PSA nadir level as early surrogates for treatment failure: analysis of a prostate cancer randomized/radiation dose escalation trial. Int J Radiat Oncol Biol Phys 54:677-685,2002.
21. Zelefsky MJ, Leibel SA, Burman CM, et al. Neoadjuvant hormonal therapy improves the therapeutic ratio in patients with bulky prostatic cancer treated with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys 29:755-761,1994.
22. Bolla M, Gonzalez D, Warde P, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 337:295-300,1997.
23. Bolla M, Collette L, Blank L, 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 360:103- 106,2002.
24. Pilepich MV, Winter K, John MJ, 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 50:1243-1252,2001.
25. Pilepich MV, Çaplan R, Byhardt RW, et al. Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31. J Clin Oncol 15:1013- 1021,1997.
26. Horwitz EM, Winter K, Hanks GE, et al. Subset analysis of RTOG 85-31 and 86-10 indicates an advantage for long-term vs. short-term adjuvant hormones for patients with locally advanced nonmetastatic prostate cancer treated with radiation therapy. Int J Radiat Oncol Biol Phys 49:947-956,2001.
27. Kuban DA, el-Mahdi AM, Schellhammer P. The significance of post-irradiation prostate biopsy with long-term follow-up. Int J Radiat Oncol Biol Phys 24:409-414,1992.
28. Kabalin JN, Hodge KK, McNeal JE, et al. Identification of residual cancer in the prostate following radiation therapy: role of transrectal ultrasound guided biopsy and prostate specific antigen. J Urol 142:326-331,1989.
29. Scardino PT, Wheeler TM. Local control of prostate cancer with radiotherapy: frequency and prognostic significance of positive results of postirradiation prostate biopsy. NCI Monogr:95- 103,1988.
30. Prestidge BR, Kaplan I, Cox RS, et al. The clinical significance of a positive post-irradiation prostatic biopsy without metastases. Int J Radiat Oncol Biol Phys 24:403-408,1992.
31. Zelefsky MJ, Leibel S A, Gaudin PB, et al. Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 41:491- 500,1998.
32. Shipley WU, Zietman AL, Hanks GE, et al. Treatment related sequelae following external beam radiation for prostate cancer: a review with an update in patients with stages Tl and T2 tumor. J Urol 152:1799-1805,1994.
33. Pilepich MV, Krall JM, Johnson RJ, et al. Extended field (periaortic) irradiation in carcinoma of the prostate—analysis of RTOG 75-06.Int J Radiat Oncol Biol Phys 12:345-351,1986. 34. Lee WR, Schultheiss TE, Hanlon AL, et al. Urinary incontinence following external-beam radiotherapy for clinically localized prostate cancer. Urology 48:95-99,1996.
35. Soffen EM, Hanks GE, Hunt MA, et al. Conformal static field radiation therapy treatment of early prostate cancer versus non-conformal techniques: a reduction in acute morbidity. Int J Radiat Oncol Biol Phys 24:485-488,1992.
36. Ten Haken RK, Perez-Tamayo C, Tesser RJ, et al. Boost treatment of the prostate using shaped, fixed fields. Int J Radiat Oncol Biol Phys 16:193-200,1989.
37. Pollack A, Zagars GK, Starkschall G, et al. Conventional vs. conformal radiotherapy for prostate cancer: preliminary results of dosimetry and acute toxicity. Int J Radiat Oncol Biol Phys 34:555-564,1996.

APA	ÖZYİĞİT G, akyol f, Önal C, SARI S, GÜRDALLI S, YAPICI B (2003). Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması. , 177 - 189.
Chicago	ÖZYİĞİT Gökhan,akyol fadıl,Önal Cem,SARI Sait,GÜRDALLI Salih,YAPICI Bülent Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması. (2003): 177 - 189.
MLA	ÖZYİĞİT Gökhan,akyol fadıl,Önal Cem,SARI Sait,GÜRDALLI Salih,YAPICI Bülent Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması. , 2003, ss.177 - 189.
AMA	ÖZYİĞİT G,akyol f,Önal C,SARI S,GÜRDALLI S,YAPICI B Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması. . 2003; 177 - 189.
Vancouver	ÖZYİĞİT G,akyol f,Önal C,SARI S,GÜRDALLI S,YAPICI B Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması. . 2003; 177 - 189.
IEEE	ÖZYİĞİT G,akyol f,Önal C,SARI S,GÜRDALLI S,YAPICI B "Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması." , ss.177 - 189, 2003.
ISNAD	ÖZYİĞİT, Gökhan vd. "Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması". (2003), 177-189.

APA	ÖZYİĞİT G, akyol f, Önal C, SARI S, GÜRDALLI S, YAPICI B (2003). Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması. Türk Hematoloji Onkoloji Dergisi, 13(4), 177 - 189.
Chicago	ÖZYİĞİT Gökhan,akyol fadıl,Önal Cem,SARI Sait,GÜRDALLI Salih,YAPICI Bülent Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması. Türk Hematoloji Onkoloji Dergisi 13, no.4 (2003): 177 - 189.
MLA	ÖZYİĞİT Gökhan,akyol fadıl,Önal Cem,SARI Sait,GÜRDALLI Salih,YAPICI Bülent Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması. Türk Hematoloji Onkoloji Dergisi, vol.13, no.4, 2003, ss.177 - 189.
AMA	ÖZYİĞİT G,akyol f,Önal C,SARI S,GÜRDALLI S,YAPICI B Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması. Türk Hematoloji Onkoloji Dergisi. 2003; 13(4): 177 - 189.
Vancouver	ÖZYİĞİT G,akyol f,Önal C,SARI S,GÜRDALLI S,YAPICI B Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması. Türk Hematoloji Onkoloji Dergisi. 2003; 13(4): 177 - 189.
IEEE	ÖZYİĞİT G,akyol f,Önal C,SARI S,GÜRDALLI S,YAPICI B "Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması." Türk Hematoloji Onkoloji Dergisi, 13, ss.177 - 189, 2003.
ISNAD	ÖZYİĞİT, Gökhan vd. "Lokalize prostat adenokanserlerinde hormon tedavisi ile birlikte küratif radyoterapi uygulaması". Türk Hematoloji Onkoloji Dergisi 13/4 (2003), 177-189.