{"id":1081,"date":"2022-05-06T16:32:39","date_gmt":"2022-05-06T16:32:39","guid":{"rendered":"https:\/\/www.cetruc.pt\/?p=1081"},"modified":"2022-10-28T15:49:55","modified_gmt":"2022-10-28T15:49:55","slug":"tratamentos-locais-alternativos","status":"publish","type":"post","link":"https:\/\/www.cetruc.pt\/en\/tratamentos-locais-alternativos\/","title":{"rendered":"Alternative Local Treatments"},"content":{"rendered":"
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1. Introduction:<\/strong><\/p>

Cryosurgery of the prostate (ACSC) and focused high-intensity ultrasound (HIFU) are currently considered as alternative therapeutic options in patients with PCa, especially if clinically localized (1-4).
Although HIFU is still considered an experimental treatment, ACSC has been recognized as a true therapeutic alternative, according to the guidelines of the American Urological Association. Both, HIFU and ACSC, were developed as minimally invasive procedures, with therapeutic efficacy, constituting important therapeutic alternatives associated with less morbidity.<\/p>

2 - Prostate surgery (CSAP)<\/strong><\/p>

The first principle of cryosurgery is the use of freezing techniques to induce cell death by:
\u2022 dehydration resulting in protein denaturation;
\u2022 direct disruption of cell membranes by ice crystals;
\u2022 vascular stasis and microthrombi, resulting in stagnation of microcirculation and ischemia;
\u2022 promotion of apoptosis (1-4).
The second principle of successful cryosurgery is related to the procedural factors that maximize neoplastic cell death, such as freezing rate, freezing time or repetition of freeze-heat cycles.
The historical evolution of cryosurgery shows us that:
\u2013 there is evidence of clinical benefit
- the morbidity associated with the procedure has greatly decreased with the emergence of new improvements in the technique.<\/p>

Freezing of the prostate is ensured by several 12-15 gauge needles placed perineally and guided by transrectal echo (TRUS). Thermal sensors are also placed at the level of the external sphincter and bladder neck, and a urethral heater is also inserted. Two freeze-thaw cycles are used under the guidance of TRUS.<\/p>

2.1 - Indication for ACSC<\/p>

Cryosurgery can be used as primary therapy or as a salvage therapy for prostate cancer.<\/p>

2.1.1 - Cryosurgery as primary therapy<\/p>

ACSC is an option in the primary treatment of organ-confined prostate cancer of any grade without evidence of metastasis (1-3). High-risk patients may undergo multimodal therapy. There are some studies concerning locally invasive disease (cT3), but the role of cryosurgery is still undetermined.
The volume and configuration of the prostate are factors to be taken into account, since the larger the volume, the more difficult it is to obtain uniform cooling of the gland, or even to have access to the entire organ through the interposition of the pubic arch. Ideally, the volume should be less than 40cc. In the case of larger prostates, patients can be submitted to neoadjuvant hormone therapy for their reduction (4a;4b).
Although many patients with elevated PSA are treated with cryosurgery, the best results were obtained with PSA below 10 ng\/ml (4a,4b).
A previous TURP may be a relative contraindication, especially if the prostatic location is large, due to difficulty in heating the urethra, with a greater risk of urethral necrosis and acute urinary retention due to clots and debris (4a,4b).
Cryosurgery is therefore a minimally invasive option for men who refuse radical prostatectomy or who are not good candidates for radical prostatectomy (comorbidities, previous pelvic surgery, obesity or narrow pelvis) and who cannot undergo radiation therapy (previous radiation therapy, inflammatory bowel disease or rectal pathology).<\/p>

2.1.2 - Cryosurgery as salvage therapy<\/p>

Cryosurgery can be considered as a therapeutic option with curative intent in patients with radiotherapy failure (external or brachytherapy). The most appropriate candidates are those with a positive biopsy for persistent organ-confined disease, no metastases and no evidence of seminal vesicle invasion, a PSA of less than 10 ng\/ml, a long PSA doubling time, and a life expectancy greater than 10 years. (4c,4d,4e). Prostate volume is not as important a factor as in the case of primary therapy, but prior TURP with a large location remains a relative contraindication.
Although there are no established parameters to define success after salvage cryosurgery, non-persistence of disease diagnosed by biopsy and a stable PSA value of less than 0.5 ng\/ml are generally used to define the technique's effectiveness.
In conclusion, cryosurgery is an option for the recurrence of organ-confined prostate cancer after radiotherapy and should be considered early in these patients. Refinements in technique and equipment have resulted in a significant reduction in morbidity and encouraging short-term results.<\/p>

2.2 - The results of cryosurgery<\/p>

When comparing treatment modalities, it is important to keep in mind that in patients with clinically organ-confined RP, there is a very low risk (2.4%) of dying from PCa 10 years after surgery (5). Therapeutic outcomes have improved over time with refinement of the technique, such as new probes and the placement of transperineal probes, as used in third-generation cryosurgery (6-11).
With regard to the second generation of ACSC, if a PSA nadir Long et al. (6) performed a retrospective analysis of the results of 975 patients undergoing ACSC, subdivided into three risk groups. Using PSA thresholds of 1.0 ng\/mL and \u2022 76% and 60%, respectively, for the low-risk group;
\u2022 71% and 45%, respectively, for the intermediate risk group;
\u2022 61% and 36%, respectively, for the high-risk group.
Cryosurgery showed progression-free survival (PFS) of 36-92% (projected 1-7 years). Negative biopsies were observed in 72-87% of cases, but there are no biopsy data for the third generation of cryotherapy.
Bahn et al. (9) analyzed 590 patients undergoing ACSC due to clinically localized and locally advanced PCa. Using a PSA level Unfortunately, we do not yet have long-term data on this technique.<\/p>

2.3 - Complications of CSAP<\/p>

Short-term complications (one week to four months) include acute urinary retention, genital swelling, and penile paresthesia.
Long-term complications include rectal fistula, urinary incontinence and erectile dysfunction.
Erectile dysfunction occurs in approximately 80% (49-93%) of patients and remains a consistent complication of the procedure, regardless of the generation of the system used. Complication rates reported in third-generation cryosurgery include tissue shedding in about 3%, incontinence in 4.4%, pelvic pain in 1.4%, and urinary retention in about 2% of patients (6-11). Fistula development is generally rare, being less than 0.2% in recent series. About 5% of patients require transurethral resection of the prostate (TURP) for obstruction.<\/p>

3 \u2013 HIFU<\/strong><\/p>

HIFU consists of the use of ultrasound waves emitted from a transducer, which cause tissue damage by mechanical and thermal effects, causing prostate cavitation (16). The purpose of HIFU is to heat malignant tissues above 65\u00b0C so that they are destroyed by coagulation necrosis.
HIFU is performed under general or locoregional anesthesia, with the patient lying in the lateral position. The procedure is time-consuming, with about 10 g of treated prostate tissue per hour.<\/p>

3.1 The HIFU results<\/p>

As with ACSC, it appears to be difficult to interpret oncological results in patients undergoing HIFU because the criteria for biochemical failure are heterogeneous and there is no international consensus.
According to a recent review (12), HIFU showed PFS (based on PSA \u00b1 biopsy) of 63-87% (projected to 3-5 years), but mean follow-up time in the studies ranged from 12-24 months only.
In one of the largest known studies, the results of 227 patients were analyzed after a mean follow-up of 27 months (range: 12-121 months) (17). At 5 years the BDFS was 66%, or only 57% if patients had displayed a pre-therapy PSA value of 4-10 ng\/ml.
Due to the lack of long-term follow-up, the procedure is still considered experimental. As a primary therapy, HIFU is indicated in patients over 70 years of age with organ-confined disease, although it has been used with encouraging results as a first-line salvage therapy after definitive treatment, particularly in patients with low\/medium risk disease. , or in locally advanced disease (T3,T4).<\/p>

3.2 - Complications of HIFU<\/p>

Morbidity is low and includes acute urinary retention, urethral stricture, urinary incontinence, erectile dysfunction and urethrorectal fistula.
Urinary retention appears to be one of the most common side effects of HIFU, developing in almost all patients between 12 and 35 days (16-18). Stress urinary incontinence occurs in about 12%. A subsequent TURP or bladder neck incision to treat the obstruction is common, and is sometimes performed at the time of HIFU. Erectile dysfunction occurs in 55-70% of patients.
Eltherman et al. (27) treated 95 patients using the Sonablate-500 device, and assessed the type and frequency of treatment-associated complications. With a minimum follow-up of 6 months, 17% (7\/41) of men had significant incontinence and 2% had erectile dysfunction. Early and late obstruction requiring surgical treatment occurred in 17 (17.9%) and 20 (21.1%) patients, respectively.<\/p>

4 - Focal therapy<\/strong><\/p>

During the last two decades, there has been a trend towards early diagnosis of PC due to greater public and professional awareness, leading to the adoption of both formal and informal screening strategies. The effect of this has been to identify men with early-stage tumors that occupy only 5-10% of the prostate volume, with a greater propensity for unifocal or unilateral disease (28-30).
Focal therapies, to date, have been achieved with ablative technologies such as cryotherapy, HIFU or photodynamic therapy. Some groups have proposed a more localized therapy, in the expectation that the genitourinary functions will be preserved and the tumor treated properly (31-33). Although focal therapy is not currently the standard for men with organ-confined PCa, it is a therapeutic approach with future potential. Although it is a conceptually attractive technique, clinical experience is limited and long-term results are unknown.<\/p>

4.1 Pre-therapeutic assessment of patients<\/p>

The current standard for characterization is prostate biopsy using a model-guided mapping approach. A 5 mm sampling frame is used to discard foci > 0.5 and 0.2 ml volume, with a 90% certainty (36). Thus, the exact location of the anatomical lesion defined as the most biologically aggressive can be accurately determined.<\/p>

4.2 Selection of patients for focal therapy<\/p>

The main goal of treatment should be the eradication of the measurable and biologically aggressive disease. However, although treatment is generally intended to be one-time, patients should know that treatment may still be necessary in the future.(34,35)
Patient selection criteria are not defined, but candidates are likely to be men with an indication for active surveillance but who prefer to be treated, or men with unilateral organ confined disease.
Based on published data, the following criteria are useful in identifying potential candidates for trials currently undergoing focal treatment:<\/p>

\u2022 Candidates for focal therapy should ideally have transperineal mapping biopsies. MRI-guided biopsies may be used alternatively.
\u2022 Focal therapy should be limited to patients at low to moderate risk. The clinical stage of the tumor should be \u2022 Patients with previous prostate surgery should be advised carefully, as there is little data on functional and oncological outcomes available.
Patients should be informed that the therapy is still experimental and that there is a possibility of repeat treatment.<\/p>

\u2022 Fahmy WE, Bissada NK. Cyrosurgery for prostate cancer. Arch Androl 2003 Sep-Oct;49(5):397-407. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12893518
\u2022 Rees J, Patel B, Macdonagh R, et al. Cryosurgery for prostate cancer. BJU Int 2004 Apr;93(6):710-4. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/15049977
\u2022 Han KR, Belldegrun AS. Third-generation cryosurgery for primary and recurrent prostate cancer. BJU Int 2004 Jan;93(1):14-8. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/14678360
\u2022 Beerlage HP, Th\u00fcroff S, Madersbacher S, et al. Current status of minimally invasive treatment options \u2028for localized prostate carcinoma. Eur Urol 2000 Jan;37(1):2-13. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/10671777<\/p>

4 a . Long JP: Is there a role for cryoablation of the prostate in the management of
localized prostate carcinoma? Hematol Oncol Clin North Am 1996; 10: 675.
4b. Bahn DK, Lee F, Silverman P, Bahn E, Badalament R, Kumar A et al: Salvage
cryosurgery for recurrent prostate cancer after radiation therapy: a seven-year
follow-up. Clin Prostate Cancer 2003; 2: 111.<\/p>

4c. Ng CK, Moussa M, Downey DB and Chin JL: Salvage cryoablation of the prostate:
followup and analysis of predictive factors for outcome. J Urol 2007; 178: 1253.
4d. Nguyen PL, D\u2019amico AV, Lee AK and Suh WW: Patient selection, cancer control,
and complications after salvage local therapy for postradiation prostate-specific
antigen failure: a systematic review of the literature. Cancer 2007; 110: 1417.
4e. Pound CR, Partin AW, Epstein JI and Walsh PC: Prostate-specific antigen after
anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer
control. Urol Clin North Am 1997; 24: 395.<\/p>

\u2022 Hull GW, Rabbani F, Abbas F, et al. Cancer control with radical prostatectomy alone in 1,000 \u2028consecutive patients. J Urol 2002 Feb;167(2Pt1):528-34. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/11792912
\u2022 Long JP, Bahn D, Lee F, et al. Five-year retrospective, multi-institutional pooled analysis of cancer- \u2028related outcomes after cryosurgical ablation of the prostate. Urology 2001 Mar;57(3):518-23. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/11248631
\u2022 Donelly BJ, Saliken JC, Ernst DS, et al. Prospective trial of cryosurgical ablation of the prostate: five \u2028year results. Urology 2002 Oct;60(4):645-9. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12385926
\u2022 Han K, Cohen J, Miller R, et al. Treatment of organ confined prostate cancer with third generation \u2028cryosurgery: preliminary multicentre experience. J Urol 2003 Oct;170(4Pt1):1126-30. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/14501706
\u2022 Bahn DK, Lee F, Baldalament R, et al. Targeted cryoablation of the prostate: 7-year outcomes in the \u2028primary treatment of prostate cancer. Urology 2002 Aug;60(2 Suppl 1):3-11. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12206842
\u2022 Koppie TM, Shinohara K, Grossfeld GD, et al. The efficacy of cryosurgical ablation of prostate cancer: \u2028the University of California, San Francisco experience. J Urol 1999 Aug;162(2):427-32. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/10411051
\u2022 De La Taille A, Benson MC, Bagiella E, et al. Cryoablation for clinically localized prostate cancer using \u2028an argon-based system: complication rates and biochemical recurrence. BJU Int 2000 Feb;85(3): 281-6.\u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/10671882
\u2022 Aus G. Current status of HIFU and cryotherapy in prostate cancer-a review. Eur Urol 2006 Nov;50(5):927-34. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16971038
\u2022 Onik G, Narayan P, Vaughan D, et al. Focal \u2018nerve-sparing\u2019 cryosurgery for treatment of primary \u2028prostate cancer: a new approach to preserving potency. Urology 2002 Jul;60(1):109-14. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12100934
\u2022 Robinson JW, Donnelly BJ, Saliken JC, et al. Quality of life and sexuality of men with prostate cancer 3 \u2028years after cryosurgery. Urology 2002 Aug;60(2 Suppl 1):12-8. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12206843
\u2022 Robinson JW, Donnelly BJ, Siever JE, et al. A randomized trial of external beam radiotherapy \u2028versus cryoablation in patients with localized prostate cancer: quality of life outcomes. Cancer 2009 Oct;115(20):4695-704.\u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19691092
\u2022 Madersbacher S, Marberger M. High-energy shockwaves and extracorporeal high-intensity focused ultrasound. J Endourol 2003 Oct;17(8):667-72.\u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/14622487
\u2022 Poissonnier L, Chapelon JY, Rouviere O, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol 2007 Feb;51(2):381-7.\u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16857310
\u2022 Gelet A, Chapelon JY, Bouvier R, et al. Local control of prostate cancer by transrectal high intensity focused ultrasound therapy: preliminary results. J Urol 1999 Jan;161(1):156-62. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/10037389
\u2022 Elterman DS, Barkin J, Radomski SB, et al. Results of high intensity focused ultrasound treatment of prostate cancer: early Canadian experience at a single center. Can J Urol 2011 Dec;18(6):6037-42. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22166332
\u2022 Mouraviev V, Mayes JM, Polascik TJ. Pathologic basis of focal therapy for early-stage prostate cancer. Nat Rev Urol 2009 Apr;6(4):205-15. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19352395
\u2022 Cooperberg MR, Broering JM, Kantoff PW, et al. Contemporary trends in low risk prostate cancer: risk \u2028assessment and treatment. J Urol 2007 Sep;178(3Pt 2):S14-9. \u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17644125
\u2022 Polascik TJ, Mayes JM, Sun L, et al. Pathologic stage T2a and T2b prostate cancer in the \u2028recent prostate-specific antigen era: implications for unilateral ablative therapy. Prostate 2008 Sep;68(13):1380-6.\u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18543281
\u2022 Ahmed HU, Pendse D, Illing R, et al. Will focal therapy become standard of care for men with localized prostate cancer? Nat Clin Pract Oncol 2007 Nov;4(11):632-42. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17965641
\u2022 Eggener SE, Scardino PT, Carroll PR, et al; International Task Force on Prostate Cancer and the Focal Lesion Paradigm. Focal therapy for localized prostate cancer: a critical appraisal of rationale and modalities. J Urol 2007 Dec;178(6):2260-7.\u2028http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17936815
\u2022 Crawford ED, Barqawi A. Targeted focal therapy: a minimally invasive ablation technique for early prostate cancer. Oncology (Williston Park) 2007 Jan;21(1):27-32. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17313155
\u2022 Onik G, Miessau M, Bostwick DG. Three-dimensional prostate mapping biopsy has a potentially significant impact on prostate cancer management. J Clin Oncol 2009 Sep;10:27(26):4321-6. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19652073
\u2022 Onik G, Barzell W. Transperineal 3D mapping biopsy of the prostate: an essential tool in selecting patients for focal prostate cancer therapy. Urol Oncol 2008 Sep-Oct;26(5):506-10. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18774464
\u2022 Crawford ED, Wilson SS, Torkko KC, et al. Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy. BJU Int 2005 Nov;96(7):999-1004. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16225516<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>","protected":false},"excerpt":{"rendered":"

1- Introdu\u00e7\u00e3o: A criocirurgia da pr\u00f3stata (CSAP) e os ultra sons de alta intensidade focalizados (HIFU) s\u00e3o, hoje em dia, considerados como op\u00e7\u00f5es terap\u00eauticas alternativas em pacientes com CaP, sobretudo se clinicamente localizado (1-4). Embora o HIFU seja ainda considerado um tratamento experimental, a CSAP tem sido reconhecida como uma verdadeira alternativa terap\u00eautica, de acordo […]<\/p>\n","protected":false},"author":3,"featured_media":3243,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"ngg_post_thumbnail":0,"cybocfi_hide_featured_image":"","footnotes":""},"categories":[1],"tags":[],"class_list":["post-1081","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"yoast_head":"\nTratamentos Locais Alternativos – CETRUC<\/title>\n<meta name=\"description\" content=\"Tratamentos Locais Alternativos – Tratamentos m\u00e9dicos que s\u00e3o utilizados em vez das terapias tradicionais (mainstream).\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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