DOI: 10.5301/urologia.5000034
Urologia 2014 ; 81 ( 1): 46-50
ORIGINAL ARTICLE
Salvage low-dose-rate brachytherapy for prostate cancer local recurrence after radical prostatectomy: our first three patients Emilio Gastaldi, Fabrizio Gallo, Luciano Chiono, Claudio Giberti Department of Urology, San Paolo Hospital, Savona - Italy
Purpose of the study: To present our initial experience with brachytherapy (BT) as a primary salvage procedure for the treatment of prostate cancer (PCa) local recurrence following radical retropubic prostatectomy (RRP). Methods: From December 2009 to May 2010, three patients underwent salvage BT due to local recurrences of high risk PCa after extrafascial RRP without additional adjuvant therapies. Local recurrence was confirmed by prostate biopsy and the relapse was well defined by endorectal ultrasonography and magnetic resonance imaging. Metastatic screening was negative. The patients were followed-up according to the American Brachytherapy Society guidelines. Results: The median dose delivered to 90% of the local relapse (D90) was 115 Gy. The three patients reached a prostate specific antigen (PSA) nadir value within the first year that remained stable at a mean follow-up of 32 months. As regards morbidity, moderate de novo urgency was reported by only one patient. Conclusions: We think that our data confirms the feasibility and safety of salvage BT as a possible alternative option to external beam radiotherapy (EBRT) for the treatment of locally recurrent PCa in selected patients when performed by experienced centers. However, larger series of patients with longer follow-ups are needed to define the oncologic role of this procedure. Key words: Salvage therapies, Brachytherapy, Prostate cancer, Prostatectomy Accepted: July 29, 2013
Introduction Radical prostatectomy (RP) is a well-established and effective option for the management of localized prostate carcinoma (PCa) (1). However, in spite of the good oncologic results reported after this procedure, a significant risk for PCa recurrence still remains. In fact, 10-50% of patients with localized PCa will have a biochemical recurrence within 10 years of initial therapy with evidence of a local relapse in 16-81% (2-6). Local recurrences after RP are generally treated with salvage radiotherapy (RT) usually 46
in combination with androgen deprivation therapy (ADT) with reported complete responses in ≥60% of patients (7-9). However, a considerable risk of adverse events, such as gastrointestinal and genitourinary symptoms, sexual dysfunction or metabolic and cardiovascular complications are commonly reported after RT and ADT, respectively (10-11). In this setting, the development of alternative options, which could provide similar good oncologic results with a lower toxicity, is an interesting and current topic for urologists. In the last decade, brachytherapy (BT) has emerged as an alternative treatment option for localized
© 2013 Wichtig Editore - ISSN 0391-5603
Gastaldi et al
PCa reporting promising mid-term results with all the advantages of a single day procedure (12). Only a few papers are reported in literature regarding the use of BT as a salvage procedure for local PCa recurrence, usually after external beam radiotherapy (EBRT) failure (13-17). Based on these few cases, it is very difficult to assess the real role of BT as a salvage procedure due to the influence of the previous EBRT on the cancer tissue. Very few studies have been published regarding the possible use of BT as a primary salvage procedure for local PCa recurrence (18-19). The aim of this paper is to present and critically evaluate our initial experience with BT as a salvage procedure for the treatment of PCa local relapse following RP.
Methods From December 2009 to May 2010, three patients underwent salvage BT due to local recurrences of high risk PCa. They had previously been treated with extrafascial radical retropubic prostatectomy (RRP) at other institutions, without additional adjuvant therapies (Tab. I). All patients had pathologic confirmation of local recurrence by prostate biopsy, and the relapse was clearly evident and well defined by endorectal ultrasonography and magnetic resonance imaging (Fig. 1). In one case (patient number 3), the local recurrence was also palpable at the digital recTable I - Patients’ characteristics before BT
Age (yr) Pathologic report after RRP
Patient nº 1
Patient nº 2
Patient nº 3
74
71
72
Staging T3aG3N0 T3bG3N0 T3bG3N0 GS
3+4
4+3
4+4
No
Yes
Yes
Interval to local recurrence (years)
6.4
6.2
5.1
Size of recurrence (cm3)
5.4
7.5
18
Pre-BT PSA (ng/mL)
2
1.58
7
Pre-BT IPSS value
4
4
10
3+4
4+4
4+4
PSM
Relapse GS
GS: Gleason score; PSM: Positive surgical margin; PSA: Prostate specific antigen; IPSS: International Prostate Symptom Score.
Fig. 1 - The PCa relapse is well defined by transrectal ultrasonography.
tal examination. Metastatic screenings with radionuclide bone scanning and positron emission tomography were negative. None of the patients reported iatrogenic urinary incontinence. The median time interval between RRP and salvage BT was 5.9 years. The Quick-Link system (Bard Medical Division, 8195 Industrial Boulevard, Covington, GA 30014, USA) was used to implant I-125 seeds using a real-time transperineal ultrasound-guided technique. Intraoperative planning with Variseed 8,1 (Varian Medical System, 3100 Hansen Way Palo Alto, CA 94304-1038, USA) was used and the prescribed dose to treat the relapse was 100-120 Gy. The planning target volume ranged from 5.40 to 18 cm3, the number of seeds ranged from 17 to 30 and the number of needles ranged from 5 to 10. The insertion of the needles was performed in a manner identical to a typical prostate implantation procedure (20). The needles were placed into the neoplastic relapse under transversal ultrasound control but their progression was monitored on a longitudinal scan to determine the insertion depth for each needle more precisely. The treatment was planned taking care to keep the needle position one centimeter from the urethrovesical anastomosis and the anterior rectal wall, in order to limit both urinary and rectal morbidities. Patients were discharged the day after BT and no additio-
© 2013 Wichtig Editore - ISSN 0391-5603
47
Salvage brachytherapy in prostate cancer
nal therapy was planned after this procedure. Patients underwent computed tomography-based dosimetry 1 month after implantation. The dose delivered to the local relapse was determined from a dose-volume histogram analysis and defined as the dose delivered to 90% of the local relapse (D90). All doses were defined according to the American Association of Physicists in Medicine Radiation Therapy Committee Task Group 43 (21). Follow-up visits were scheduled every 3 months for the first year after BT and then every 6 months. Post-operative evaluation was performed in accordance with the American Brachytherapy Society guidelines including history, physical examination, prostate specific antigen (PSA) assay and International Prostate Symptom Score (IPSS) questionnaire compilation (22-23). Mean follow-up was 32 months.
Results Patients’ characteristics at salvage brachytherapy are shown in Table I and post-operative outcomes are reported in Table II. The median D90 of nodule was 115 Gy. After BT, all three patients reached a PSA nadir value Table II - Patients’ outcomes after BT Patient nº 1
Patient nº 2
Patient nº 3
100
120
115
Number of I-125 seeds implanted (n)
17
18
30
I-125 seeds total activity (mCi)
4.5
5.35
18.3
Number of needles positioned (n)
5
6
10
V150 Urethra (cm )
0
0.01
0.37
V100 Rectum (cm )
0.01
0.02
1.68
0.1
0.01
0.1
9
12
12
PSA value at last follow-up visit (ng/mL)
0.1
0.01
0.1
Morbidity (de novo urgency)
None
None
Yes
35
33
28
D90 of nodule (Gy)
3
3
PSA nadir value after salvage BT (ng/mL) Interval to PSA nadir value (mo)
Follow-up (months)
D90: minimal dose received by 90% of target volume; V150 Urethra: volume of the urethra receiving over 150% of the prescribed dose; V100 Rectum: volume of the rectum receiving over 100% of the prescribed dose; PSA: Prostate specific antigen.
48
Fig. 2 - Dose distribution achieved during post-implant planning at 1 month. Local relapse and I-125 seeds implanted are well shown.
within the first year that remained stable at a mean followup of 32 months. As regards morbidity, de novo urgency, with moderate increase of the pre-operative IPSS score, was only reported by the third patient. None of the patients reported urinary incontinence, hematuria or proctitis. All of the patients reported erectile dysfunction before BT and this was unchanged in post-procedural follow-up. None of the patients received ADT after the procedure. Figure 2 shows the dose distribution achieved during postimplant planning at 1 month.
Discussion There are very few reported series of patients undergoing salvage BT after RP and those that have been published generally involve small numbers of patients treated with BT and combined EBRT or after EBRT failure (13-17). Based on these few cases, it is very difficult to assess the real role of BT as a primary salvage procedure due to the influence of the EBRT on the cancer tissue. More recently, Traudt et al. reported an initial experience with salvage BT for local recurrence of PCa after radical
© 2013 Wichtig Editore - ISSN 0391-5603
Gastaldi et al
prostatectomy without any other adjuvant treatment. The authors showed a remarkable decline in PSA level and a very low morbidity rate in all the five patients treated at a median follow-up of 13 months (18). Similar promising outcomes have been reported in the newer review by Gomez-Veiga et al. at a follow-up of 5 years (19). Our data confirmed a progressive decline of PSA values up to the nadir value (0.1 ng/ mL) within 12 months from implantation, which remained stable at a mean follow-up of 32 months. This decrease of PSA has been even quicker than the one we are used to seeing after BT for primary PCa. This aspect could be due to the elective implantation of the seeds into the tumor, which is a smaller target than the entire prostate, producing an earlier PSA response. However, this hypothesis greatly needed to be confirmed in the future. Furthermore, we did not assess any particular morbidity after salvage BT, except for a moderate urgency in one patient. As already pointed out by Traudt et al., these results seemed to compare favorably with those reported after EBRT, showing a good control of PCa local recurrence but a higher genitourinary and gastrointestinal toxicity (18-19, 24-25). These aspects could suggest the potential role of salvage BT as an alternative option to EBRT for PCa local recurrence due to the promising short-term oncologic results and the lower toxicity rate, with the additional advantages of patient convenience (18-19). However, some important aspects tend to limit the role of salvage BT for the treatment of local PCa recurrence. Firstly, our data, as well as the few others available in literature, are based on a small number of patients and a short follow-up. Thus, before reaching any oncologic conclusion, further results are strongly needed in order to compare BT versus EBRT for this particular condition. Secondly, the identification of a visible target by transrectal ultrasonography is an indispensable requirement in order to perform salvage BT, representing an important limit for its reproducibility in most cases of PCa local recurrences. Thirdly, an extended skill in BT for primary PCa is real-
References 1.
ly advisable before performing a salvage BT procedure. In fact, particular accuracy in the volume study and preplan dosimetry assessments are mandatory in order to evaluate the adequate dose coverage of the target and to spare the surrounding critical organs. Furthermore, the insertion of the needles must be performed very carefully due to the small dimension and the critical position of the target. Finally, as already reported and confirmed by our present experience, the use of stranded seeds, which provides a more stable seed envelope and prevents their migration or displacement, seems to be much more useful in these cases due to the asymmetry and irregularity of the local recurrence (13, 19, 26). This aspect would also suggest the importance of skill in the use of stranded seeds in order to achieve better results with lower morbidity. Basing on these aspects we think that our data confirm the feasibility and safety of salvage BT as a possible alternative option to EBRT for the treatment of PCa local recurrence in selected patients when performed by experienced centers. Larger series of patients with longer follow-ups are needed to define the oncologic role of this procedure. Disclaimers Informed consent: Informed consent was obtained by all participants. The manuscript does not report the results of an experimental investigation on human subjects. Financial support: The authors did not receive any financial support for this study. Conflict of interest: No conflict of interest was identified.
Corresponding Author: Fabrizio Gallo Department of Urology San Paolo Hospital Via Genova 30 17100 Savona, Italy [email protected]
2.
Mottet N, Bellmunt J, Bolla M, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing and castration-resistant prostate cancer. Eur Urol. 2011;59: 572-583.
3.
Boorjian S.A, Thompson R.H, Tollefson MK, et al. Long-term risk of clinical progression after biochemical recurrence following radical prostatectomy: the impact of time from surgery to recurrence. Eur Urol. 2011;57:893-899. Kupelian PA, Elshaikh M, Reddy CA, Zippe C, Klein EA. Comparison of the efficacy of local therapies for localized
© 2013 Wichtig Editore - ISSN 0391-5603
49
Salvage brachytherapy in prostate cancer
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prostate cancer in the prostate-specific antigen era: a large single-institution experience with radical prostatectomy and external-beam radiotherapy. J Clin Oncol. 2002;20: 3376-3385. Stephenson AJ, Scardino PT, Eastham JA, et al. Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Natl Cancer Inst. 2006;98:715-717. Raj GV, Partin AW, Polascik TJ. Clinical utility of indium 111-capromab pendetide immunoscintigraphy in the detection of early, recurrent prostate carcinoma after radical prostatectomy. Cancer. 2002;94:987-996. Sella T, Schwartz LH, Swindle PW, et al. Suspected local recurrence after radical prostatectomy: endorectal coil MR imaging. Radiology. 2004;231:379-385. Stephenson AJ, Scardino PT, Kattan MW, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol. 2007;25: 2035-2041. Katz MS, Zelefsky MJ, Venkatraman ES, Fuks Z, Hummer A, Leibel SA. Predictors of biochemical outcome with salvage conformal radiotherapy after radical prostatectomy for prostate cancer. J Clin Oncol. 2003;21:483-489. Pazona JF, Han M, Hawkins SA, Roehl KA, Catalona WJ. Salvage radiation therapy for prostate specific antigen progression following radical prostatectomy: 10 years outcome estimates. J Urol. 2005;174:1282-1286. Wu AK, Cooperberg MR, Sadetsky N, Carroll PR. Health related quality of life in patients treated with multimodal therapy for prostate cancer. J Urol. 2008;180:2415-2418. Smith MR. Changes in fat and lean body mass during androgen deprivation therapy for prostate cancer. Urology. 2004;63:742-745. Crook J. The role of brachytherapy in the definitive management of prostate cancer. Cancer Radiother. 2011;15: 230-237. Losa A, Nava LD, Di Muzio N, et al. Salvage brachytherapy for local recurrence after radical prostatectomy and subsequent external beam radiotherapy. Urology. 2003;62: 1068-1072. Niehoff P, Loch T, Nurnberg N, et al. Feasibility and preliminary outcome of salvage combined HDR brachytherapy and external beam radiotherapy (EBRT) for local recur-
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rences after radical prostatectomy. Brachytherapy. 2005;4: 141-145. Lee HK, Adams MT, Motta J. Salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy. Brachytherapy. 2008;7:17-21. Burri RJ, Stone NN, Unger P, Stock RG. Long term outcome and toxicity of salvage brachytherapy for local failure after initial radiotherapy for prostate. Int J Radiat Oncol Biol Phys. 2010;77:1338-1344. Gaztanaga M, Crook JM. Permanent seed brachytherapy for locally recurrent prostate cancer after radical prostatectomy: A case report and review of the literature. Brachytherapy. 2012; 27. Traudt K, Ciezki J, Klein EA. Low-dose-rate brachytherapy as salvage treatment of local prostate cancer recurrence after radical prostatectomy. Urology. 2011;77:1416-1419. Gomez-Veiga F, Marino A, Alvarez L, et al. Brachytherapy for the treatment of recurrent prostate cancer after radiotherapy or radical prostatectomy. BJU Int. 2012;1:17-21. Stone NN, Stock RG. Permanent seed implantation for localized adenocarcinoma of the prostate. Curr Urol Rep. 2002;3:201-206. Williamson JF, Butler W, Dewerd LA, et al. Recommendations of the American Association of Physicist in Medicine regarding the impact of implementing the 2004 task group 43 report on dose specification for 103 Pd and 125 I interstitial brachytherapy. Med Phys. 2005;32:1424-1439. Nag S, Bice W, De Wyngaert JK, Prestidge B, Stock R, Yu Y. The American Brachytherapy Society recommendations for permanent prostate brachytherapy postimplant dosimetric analysis. Int J Radiat Oncol Biol Phys. 2000;46:221-230. Barry MJ, Fowler FJ, O’Leary MP, et al. The American Urological Association symptom index for benign prostatic hyperplasia. J Urol. 1992;148:1549-1556. Choo R. Salvage radiotherapy for patients with PSA relapse following radical prostatectomy: issues and challenges. Cancer Res Treat. 2010;42:1-11. Brooks JP, Albert PS, Wilder RB, Gant DA, McLeod DG, Poggi MM. Long-term salvage radiotherapy outcome after radical prostatectomy and relapse predictors. J Urol. 2005;174:2204-2208. Gastaldi E, Chiono L, Gallo F, et al. Brachytherapy in prostate cancer: the use of QuickLink® system within the real-time technique. A new technique is presented. Urologia. 2009;76: 41-44.
© 2013 Wichtig Editore - ISSN 0391-5603
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Urologia 2014 ; 81 ( 1): 46-50
ORIGINAL ARTICLE
Salvage low-dose-rate brachytherapy for prostate cancer local recurrence after radical prostatectomy: our first three patients Emilio Gastaldi, Fabrizio Gallo, Luciano Chiono, Claudio Giberti Department of Urology, San Paolo Hospital, Savona - Italy
Purpose of the study: To present our initial experience with brachytherapy (BT) as a primary salvage procedure for the treatment of prostate cancer (PCa) local recurrence following radical retropubic prostatectomy (RRP). Methods: From December 2009 to May 2010, three patients underwent salvage BT due to local recurrences of high risk PCa after extrafascial RRP without additional adjuvant therapies. Local recurrence was confirmed by prostate biopsy and the relapse was well defined by endorectal ultrasonography and magnetic resonance imaging. Metastatic screening was negative. The patients were followed-up according to the American Brachytherapy Society guidelines. Results: The median dose delivered to 90% of the local relapse (D90) was 115 Gy. The three patients reached a prostate specific antigen (PSA) nadir value within the first year that remained stable at a mean follow-up of 32 months. As regards morbidity, moderate de novo urgency was reported by only one patient. Conclusions: We think that our data confirms the feasibility and safety of salvage BT as a possible alternative option to external beam radiotherapy (EBRT) for the treatment of locally recurrent PCa in selected patients when performed by experienced centers. However, larger series of patients with longer follow-ups are needed to define the oncologic role of this procedure. Key words: Salvage therapies, Brachytherapy, Prostate cancer, Prostatectomy Accepted: July 29, 2013
Introduction Radical prostatectomy (RP) is a well-established and effective option for the management of localized prostate carcinoma (PCa) (1). However, in spite of the good oncologic results reported after this procedure, a significant risk for PCa recurrence still remains. In fact, 10-50% of patients with localized PCa will have a biochemical recurrence within 10 years of initial therapy with evidence of a local relapse in 16-81% (2-6). Local recurrences after RP are generally treated with salvage radiotherapy (RT) usually 46
in combination with androgen deprivation therapy (ADT) with reported complete responses in ≥60% of patients (7-9). However, a considerable risk of adverse events, such as gastrointestinal and genitourinary symptoms, sexual dysfunction or metabolic and cardiovascular complications are commonly reported after RT and ADT, respectively (10-11). In this setting, the development of alternative options, which could provide similar good oncologic results with a lower toxicity, is an interesting and current topic for urologists. In the last decade, brachytherapy (BT) has emerged as an alternative treatment option for localized
© 2013 Wichtig Editore - ISSN 0391-5603
Gastaldi et al
PCa reporting promising mid-term results with all the advantages of a single day procedure (12). Only a few papers are reported in literature regarding the use of BT as a salvage procedure for local PCa recurrence, usually after external beam radiotherapy (EBRT) failure (13-17). Based on these few cases, it is very difficult to assess the real role of BT as a salvage procedure due to the influence of the previous EBRT on the cancer tissue. Very few studies have been published regarding the possible use of BT as a primary salvage procedure for local PCa recurrence (18-19). The aim of this paper is to present and critically evaluate our initial experience with BT as a salvage procedure for the treatment of PCa local relapse following RP.
Methods From December 2009 to May 2010, three patients underwent salvage BT due to local recurrences of high risk PCa. They had previously been treated with extrafascial radical retropubic prostatectomy (RRP) at other institutions, without additional adjuvant therapies (Tab. I). All patients had pathologic confirmation of local recurrence by prostate biopsy, and the relapse was clearly evident and well defined by endorectal ultrasonography and magnetic resonance imaging (Fig. 1). In one case (patient number 3), the local recurrence was also palpable at the digital recTable I - Patients’ characteristics before BT
Age (yr) Pathologic report after RRP
Patient nº 1
Patient nº 2
Patient nº 3
74
71
72
Staging T3aG3N0 T3bG3N0 T3bG3N0 GS
3+4
4+3
4+4
No
Yes
Yes
Interval to local recurrence (years)
6.4
6.2
5.1
Size of recurrence (cm3)
5.4
7.5
18
Pre-BT PSA (ng/mL)
2
1.58
7
Pre-BT IPSS value
4
4
10
3+4
4+4
4+4
PSM
Relapse GS
GS: Gleason score; PSM: Positive surgical margin; PSA: Prostate specific antigen; IPSS: International Prostate Symptom Score.
Fig. 1 - The PCa relapse is well defined by transrectal ultrasonography.
tal examination. Metastatic screenings with radionuclide bone scanning and positron emission tomography were negative. None of the patients reported iatrogenic urinary incontinence. The median time interval between RRP and salvage BT was 5.9 years. The Quick-Link system (Bard Medical Division, 8195 Industrial Boulevard, Covington, GA 30014, USA) was used to implant I-125 seeds using a real-time transperineal ultrasound-guided technique. Intraoperative planning with Variseed 8,1 (Varian Medical System, 3100 Hansen Way Palo Alto, CA 94304-1038, USA) was used and the prescribed dose to treat the relapse was 100-120 Gy. The planning target volume ranged from 5.40 to 18 cm3, the number of seeds ranged from 17 to 30 and the number of needles ranged from 5 to 10. The insertion of the needles was performed in a manner identical to a typical prostate implantation procedure (20). The needles were placed into the neoplastic relapse under transversal ultrasound control but their progression was monitored on a longitudinal scan to determine the insertion depth for each needle more precisely. The treatment was planned taking care to keep the needle position one centimeter from the urethrovesical anastomosis and the anterior rectal wall, in order to limit both urinary and rectal morbidities. Patients were discharged the day after BT and no additio-
© 2013 Wichtig Editore - ISSN 0391-5603
47
Salvage brachytherapy in prostate cancer
nal therapy was planned after this procedure. Patients underwent computed tomography-based dosimetry 1 month after implantation. The dose delivered to the local relapse was determined from a dose-volume histogram analysis and defined as the dose delivered to 90% of the local relapse (D90). All doses were defined according to the American Association of Physicists in Medicine Radiation Therapy Committee Task Group 43 (21). Follow-up visits were scheduled every 3 months for the first year after BT and then every 6 months. Post-operative evaluation was performed in accordance with the American Brachytherapy Society guidelines including history, physical examination, prostate specific antigen (PSA) assay and International Prostate Symptom Score (IPSS) questionnaire compilation (22-23). Mean follow-up was 32 months.
Results Patients’ characteristics at salvage brachytherapy are shown in Table I and post-operative outcomes are reported in Table II. The median D90 of nodule was 115 Gy. After BT, all three patients reached a PSA nadir value Table II - Patients’ outcomes after BT Patient nº 1
Patient nº 2
Patient nº 3
100
120
115
Number of I-125 seeds implanted (n)
17
18
30
I-125 seeds total activity (mCi)
4.5
5.35
18.3
Number of needles positioned (n)
5
6
10
V150 Urethra (cm )
0
0.01
0.37
V100 Rectum (cm )
0.01
0.02
1.68
0.1
0.01
0.1
9
12
12
PSA value at last follow-up visit (ng/mL)
0.1
0.01
0.1
Morbidity (de novo urgency)
None
None
Yes
35
33
28
D90 of nodule (Gy)
3
3
PSA nadir value after salvage BT (ng/mL) Interval to PSA nadir value (mo)
Follow-up (months)
D90: minimal dose received by 90% of target volume; V150 Urethra: volume of the urethra receiving over 150% of the prescribed dose; V100 Rectum: volume of the rectum receiving over 100% of the prescribed dose; PSA: Prostate specific antigen.
48
Fig. 2 - Dose distribution achieved during post-implant planning at 1 month. Local relapse and I-125 seeds implanted are well shown.
within the first year that remained stable at a mean followup of 32 months. As regards morbidity, de novo urgency, with moderate increase of the pre-operative IPSS score, was only reported by the third patient. None of the patients reported urinary incontinence, hematuria or proctitis. All of the patients reported erectile dysfunction before BT and this was unchanged in post-procedural follow-up. None of the patients received ADT after the procedure. Figure 2 shows the dose distribution achieved during postimplant planning at 1 month.
Discussion There are very few reported series of patients undergoing salvage BT after RP and those that have been published generally involve small numbers of patients treated with BT and combined EBRT or after EBRT failure (13-17). Based on these few cases, it is very difficult to assess the real role of BT as a primary salvage procedure due to the influence of the EBRT on the cancer tissue. More recently, Traudt et al. reported an initial experience with salvage BT for local recurrence of PCa after radical
© 2013 Wichtig Editore - ISSN 0391-5603
Gastaldi et al
prostatectomy without any other adjuvant treatment. The authors showed a remarkable decline in PSA level and a very low morbidity rate in all the five patients treated at a median follow-up of 13 months (18). Similar promising outcomes have been reported in the newer review by Gomez-Veiga et al. at a follow-up of 5 years (19). Our data confirmed a progressive decline of PSA values up to the nadir value (0.1 ng/ mL) within 12 months from implantation, which remained stable at a mean follow-up of 32 months. This decrease of PSA has been even quicker than the one we are used to seeing after BT for primary PCa. This aspect could be due to the elective implantation of the seeds into the tumor, which is a smaller target than the entire prostate, producing an earlier PSA response. However, this hypothesis greatly needed to be confirmed in the future. Furthermore, we did not assess any particular morbidity after salvage BT, except for a moderate urgency in one patient. As already pointed out by Traudt et al., these results seemed to compare favorably with those reported after EBRT, showing a good control of PCa local recurrence but a higher genitourinary and gastrointestinal toxicity (18-19, 24-25). These aspects could suggest the potential role of salvage BT as an alternative option to EBRT for PCa local recurrence due to the promising short-term oncologic results and the lower toxicity rate, with the additional advantages of patient convenience (18-19). However, some important aspects tend to limit the role of salvage BT for the treatment of local PCa recurrence. Firstly, our data, as well as the few others available in literature, are based on a small number of patients and a short follow-up. Thus, before reaching any oncologic conclusion, further results are strongly needed in order to compare BT versus EBRT for this particular condition. Secondly, the identification of a visible target by transrectal ultrasonography is an indispensable requirement in order to perform salvage BT, representing an important limit for its reproducibility in most cases of PCa local recurrences. Thirdly, an extended skill in BT for primary PCa is real-
References 1.
ly advisable before performing a salvage BT procedure. In fact, particular accuracy in the volume study and preplan dosimetry assessments are mandatory in order to evaluate the adequate dose coverage of the target and to spare the surrounding critical organs. Furthermore, the insertion of the needles must be performed very carefully due to the small dimension and the critical position of the target. Finally, as already reported and confirmed by our present experience, the use of stranded seeds, which provides a more stable seed envelope and prevents their migration or displacement, seems to be much more useful in these cases due to the asymmetry and irregularity of the local recurrence (13, 19, 26). This aspect would also suggest the importance of skill in the use of stranded seeds in order to achieve better results with lower morbidity. Basing on these aspects we think that our data confirm the feasibility and safety of salvage BT as a possible alternative option to EBRT for the treatment of PCa local recurrence in selected patients when performed by experienced centers. Larger series of patients with longer follow-ups are needed to define the oncologic role of this procedure. Disclaimers Informed consent: Informed consent was obtained by all participants. The manuscript does not report the results of an experimental investigation on human subjects. Financial support: The authors did not receive any financial support for this study. Conflict of interest: No conflict of interest was identified.
Corresponding Author: Fabrizio Gallo Department of Urology San Paolo Hospital Via Genova 30 17100 Savona, Italy [email protected]
2.
Mottet N, Bellmunt J, Bolla M, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing and castration-resistant prostate cancer. Eur Urol. 2011;59: 572-583.
3.
Boorjian S.A, Thompson R.H, Tollefson MK, et al. Long-term risk of clinical progression after biochemical recurrence following radical prostatectomy: the impact of time from surgery to recurrence. Eur Urol. 2011;57:893-899. Kupelian PA, Elshaikh M, Reddy CA, Zippe C, Klein EA. Comparison of the efficacy of local therapies for localized
© 2013 Wichtig Editore - ISSN 0391-5603
49
Salvage brachytherapy in prostate cancer
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
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