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Are we able to correctly identify prostate cancer patients who could be adequately treated by focal therapy?
Urologic Oncology: Seminars and Original Investigations 30 (2012) 794 –797
Original article
Are we able to correctly identify prostate cancer patients who could be adequately treated by focal therapy? Betina Katz, M.D.a, Miguel Srougi, M.D., Ph.D.b, Marcos Dall’Oglio, M.D., Ph.D.b, Adriano J. Nesrallah, M.D., Ph.D.b, Alexandre C. Sant’Anna, M.D., Ph.D.a, José Pontes Jr., M.D., Ph.D.b, Sabrina T. Reis, M.Sc.b, Adriana Sañudo, Ph.D.b, Luiz H. Camara-Lopes, M.D.a, Katia R.M. Leite, M.D., Ph.D.a,b,* b
a Laboratory of Surgical and Molecular Pathology, Sao Paulo, Brazil Laboratory of Medical Investigation, Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil
Received 26 July 2010; received in revised form 31 August 2010; accepted 29 October 2010
Abstract Introduction and Objective: Because of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer (PC) has been proposed for patients with low-risk disease. Such treatment would allow the control of cancer, thereby diminishing side effects, such as urinary incontinence and sexual dysfunction, which have an enormous impact on quality of life. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy. Our aim is to determine whether there is any preoperative feature that can help select the ideal patient for focal therapy. Material and methods: A total of 599 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy followed by radical prostatectomy to treat PC were examined in our laboratory between 2001 and 2009. We established very restricted criteria to select patients with very-low-risk disease for whom focal therapy would be suitable (only 1 biopsy core positive, tumor no larger than 80% of a single core, no perineural invasion, PSA serum level ⬍ 10 ng/ml, Gleason score ⬍ 7 and clinical stage T1c, T2a– b). We defined 2 groups of patients who would be either adequately treated or not treated by focal therapy. The primary endpoint was the evaluation of preoperative features in order to identify which parameters should be considered when choosing good candidates for focal therapy. Results: Fifty-six out of 599 patients met our criteria. The mean age was 59 years, and the mean number of biopsy cores was 14.4. Forty-seven (83.9%) were staged T1c, and 9 (16.1%) were staged T2a– b. Forty-four (78.6%) patients could be considered to have been adequately treated by focal therapy, and 12 (21.4%) could not. There was no statistical difference between the 2 groups considering age, clinical stage, PSA levels, Gleason score, and tumor volume in the biopsy. All 12 patients who could be considered inadequately treated had a bilateral, significant secondary tumor, 58.3% had Gleason ⱖ 7, and 25% were staged pT3. Conclusion: Although focal therapy might be a good option for patients with localized prostate cancer, we are so far unable to select which of them would benefit from it based on preoperative data, even using very restricted criteria, and a considerable proportion of men would still be left undertreated. © 2012 Elsevier Inc. All rights reserved. Keywords: Focal therapy; Risk stratification multifocal; Index lesion
1. Introduction Because of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer has been proposed for patients with very-low-risk or low-risk disease [1]. Such treatment ranges from precise lesion targeted ablation to subtotal gland treat* Corresponding author. Tel.: ⫹55-11-30617183; fax: ⫹55-11-32312249. E-mail address: [email protected] (K.R. Moreira Leite). 1078-1439/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.urolonc.2010.10.010
ment and has been offered as a means of treating with efficacy prostate cancer diminishing possible damage to the vital structures essential for maintaining normal urinary and sexual function without compromising cancer control [2]. An increasing number of men with low-risk prostate cancer may be overtreated with the conventional whole gland therapy: 11% of those submitted to radical prostatectomy (RP), and 45% received radiation therapy [3]. Even though many of them would have the option of active surveillance, this approach has not gained popularity be-
B. Katz et al. / Urologic Oncology: Seminars and Original Investigations 30 (2012) 794 –797
795
Fig. 1. Classification of patients as either adequately or inadequately treated by focal therapy.
cause observational strategies can lead to significant anxiety [2,4]. It is believed that 20% to 30% of men with low-risk prostate cancer in the U.S. could be candidates for parenchyma-preserving approaches [3]. The main challenge is to preoperatively identify the patients who have real low-grade adenocarcinoma based on the clinical and biopsy data. Nonetheless, the question as to whether these data are sufficiently accurate to decide for a partial ablation of the prostate while guaranteeing cancer curability still remains. The aim of our study is to determine which preoperative features can help select the ideal patients for focal therapy in a highly restricted group of patients regarded as harboring a very-low-risk adenocarcinoma.
was bilateral or there was a clinically significant secondary lesion, characterized by tumor volume ⬎ 0.05 cm3, Gleason score ⬎ 6, positive surgical margins, or extraprostatic extension. The primary endpoint was to determine the preoperative features that could correctly identify which patients should be considered good candidates for focal therapy. Statistical analyses were performed by using SPSS ver. 15.0 (SPSS Inc., Chicago, IL), and for standardization the non-parametric Mann-Whitney test was used for all numeric parameters. The exact Fisher test was used for categorical parameters. Statistical significance was considered when P ⬍ 0.05.
3. Results 2. Materials and methods A total of 599 patients who underwent transrectal ultrasound-guided prostate biopsy followed by RP for prostate cancer were examined in our laboratory from January 2001 to October 2009. All patients were treated by a single surgeon, and all the biopsies and surgical specimens were examined by the same uropathologist. The RP specimens were always examined in toto. Patients with low-risk features for whom focal therapy would be suitable were selected based on the following inclusion criteria: a single biopsy core positive; tumor extent present in less than 80% of a single core; no perineural invasion identified; PSA serum level ⬍ 10 ng/ml; Gleason score ⬍ 7; and clinical stage T1c, T2a, or T2b. In total, 56 patients met the inclusion criteria, and after treatment they were divided into 2 groups (Fig. 1). The first group was defined as adequately treated, which means that the tumor was unilateral and the secondary lesion, if present, was not clinically significant. The other group was defined as inadequately treated; in these patients the tumor
Of 599 men, 56 patients met our criteria. Forty-seven (83.9%) were staged T1c and 9 (16.1%) were staged T2a– b. The clinical and histologic data of all patients are presented in Table 1. Analyzing the radical prostatectomy specimens, 34 (60.7%) adenocarcinomas were bilateral and 30 (53.6%) were multifocal. The mean volume of the index tumor was 1.8 cm3, median 1.4 cm3, ranging from 0.3 to 8.3 cm3. Only 1 patient had an insignificant index tumor. The secondary,
Table 1 Clinical and histopathologic data of patients that could be eligible for focal therapy
Mean Median Minimum Maximum
Age (years)
N of cores
Gleason score
Greatest % of a single core
Total % of tumor
59 59 39 76
14.4 14 6 28
5.8 6 4 6
23.2 20 5 70
1.9 1.4 0.4 12
796
B. Katz et al. / Urologic Oncology: Seminars and Original Investigations 30 (2012) 794 –797
smaller tumors ranged from 0.1 to 4.9 cm3, median 0.4 cm3 and mean 0.84 cm3. Twelve (21.4%) index tumors were present at the contralateral lobe considering the biopsy result, 3 of them containing Gleason pattern 4. Twenty-two (39.2%) patients had the Gleason score increased from ⱕ6 to ⱖ7. Only 4 patients had extraprostatic extension, and only 3 patients had positive margins. Of the 56 patients, 44 (78.6%) could be adequately treated, meaning that the biopsy results localized the correct lobe affected by the index tumor. Another factor we considered a positive correlation was the detection of an insignificant secondary tumor (⬍0.5 cm3, Gleason ⬍7, organconfined) at the RP. Twelve (21.4%) patients would not have been adequately treated with focal therapy because the tumor was bilateral and/or the secondary tumor could not be considered insignificant. Seven (58.3%) had Gleason 7 or 8, and 3 (25%) were staged pT3a. The patients were distributed as follows: 5 (41.7%) had secondary tumor with Gleason score 7 and significant tumor volume (⬎0.5 cm3); 3 (25.0%) had Gleason score 7 or 8, significant tumor volume and were staged pT3, and 4 (33.3%) had tumor larger than 0.5 cm3. After analyzing whether any preoperative feature would help us to determine the patient’s suitability for focal therapy, neither clinical nor histologic characteristics were able to identify the correct group of tumors (Table 2).
4. Discussion By selecting a very restricted group of patients and considering only the most favorable preoperative data, we were able to show that 78.6% of patients would be treated appropriately by focal therapy, which means that an isolated or an index significant tumor would be ablated. Curiously, no preoperative data were able to identify the 21.4% of patients with significant contralateral adenocarcinomas. Table 2 Clinical and histopathologic data of patients that could or could not be treated adequately with focal therapy Treatment
Age (mean) Clinical stage T1 T2 PSA (ng/ml) Gleason score 4 5 6 Total % of tumor (mean) Greatest % of tumor in a single core (mean)
P
Inadequate 12 (21.4%)
Adequate 44 (78.6%)
61.7
58.2
10 (83.3%) 2 (16.7%) 6.6
37 (84.1%) 7 (15.9%) 5.1
⬎0.999 0.355
0 3 (25%) 9 (75%) 2 25.8
1 (2.3%) 5 (11.4%) 38 (86.4%) 1.8 22.5
0.491 0.494 0.457
0.317
Other researchers have also tried to determine whether it is possible to identify the ideal candidates for preservative therapies, but the preoperative aspects were not as restrictive as ours [1,2]. The strong point of our study is the high restraining clinical and histopathologic criteria that could indicate the ideal candidate for the focal treatment. Similar to our findings, Scales et al. [5] described patients with low-risk prostate cancer (stage T1c or T2a, PSA levels ⬍ 10, Gleason ⱕ 6, 1 or 2 ipsilateral positive cores), showing that only 35.1% had unilateral disease in RP specimens and that no clinical or pathologic feature was related to pathologically unilateral or bilateral disease on the multivariate analysis. In contrast to our data, Bolenz et al. [6] found that higher PSA levels, higher clinical stage, and a higher Gleason score at biopsy were independent predictors of tumor upgrading. In their series, 40.3% of tumors involved the prostatic capsule on the negative biopsy side. But in their study, the only criterion for selection of the patients was the occurrence of a unilateral tumor at the biopsy; almost one-third of the biopsies scored Gleason 7 or higher. Some authors argue that focal treatment is inadequate for a multifocal and heterogeneous tumor such as prostate cancer. Multifocal prostate cancer is present in up to 87% of RP specimens [7], and the efficacy of biopsy in identifying laterality still remains poor. In addition, only 15% to 35% of men with unilateral disease on biopsy have unilateral cancer in the RP specimen [5]. However, about 80% of non-index tumors could be considered insignificant, with small volume (ⱕ0.5 cm) and without the most aggressive Gleason pattern (Gleason 4 or 5), suggesting that the index tumor is the main determinant of prognosis and that focal therapy would eradicate the known cancer focus with the highest likelihood of progression [2,7]. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy to recommend subtotal therapy. Only a few studies determined the correlation between prostate biopsy findings and pathologic outcome after RP. Prostate biopsy accounts for significant undergrading in up to one-third of all patients [8], and an initial transrectal ultrasound (TRUS) biopsy might miss tumor areas in up to 30% of patients. The most frequent location of undetected cancer is in the dorsolateral region, anterior, and the apex of the prostate, which are not always represented in current biopsy strategies [6]. The number of cores needed to adequately sample the prostate is unknown and has been related to the size of the gland. In our study, the mean and median number of cores was 14.4 and 14, respectively, with a number higher than the 10 to 12 recommended for prostate cancer diagnosis. Some authors have proposed using extended prostate biopsy strategies to help increase cancer detection and the identification of tumors with unfavorable characteristics that would impose a more aggressive treatment [9]. Falzarano et al. found that all bilateral tumors detected by extended biopsy were confirmed to be bilateral in the RP, but only
B. Katz et al. / Urologic Oncology: Seminars and Original Investigations 30 (2012) 794 –797
10% of the patients with unilateral adenocarcinomas had unilateral cancer. However, most missed tumor foci (76%) were clinically insignificant [10]. Therefore, a negative extended biopsy does not confirm the absence of cancer in the corresponding side of the gland and cannot be used as a single determinant when considering a patient for focal treatment. Modern imaging technology, especially MRI and magnetic resonance spectroscopic imaging, could help in directing the needle toward areas of suspected cancer involvement [11]. Also, imaging before treatment could determine the tumor’s location as well as its volume and could exclude a more extensive cancer [12]. MRI of the prostate using novel techniques such as dynamic contrast enhancement and diffusion-weighted imaging are increasingly being used to stage primary prostate cancer, with excellent results. The evaluation of outcome and follow-up of patients submitted to focal therapy is still unknown, and there is no data on long-term outcomes such as functional status, oncologic efficacy, and the impact on subsequent therapy. If patients with true unilateral disease have better outcome, whole gland treatment could be avoided in these patients. The difficulty still lies in identifying which men could benefit from a less aggressive modality of treatment without compromising cancer curability.
5. Conclusion Even though focal therapy might be a good option for patients with localized prostate cancer, as of now there is no data that could adequately select which of them would benefit from it based on preoperative data, even being extremely restricted in the selection of patients. Characteristics such as age, clinical stage, PSA levels, percentage of the tumor in a single core, and total percentage of the tumor in
797
the biopsy did not add any further information about the ideal patient for focal therapy.
References [1] Mayes JM, Mouraviev V, Sun L, et al. Can the conventional sextant prostate biopsy accurately predict unilateral prostate cancer in lowrisk, localized, prostate cancer? Urol Oncol 2011;29(2):166 –70. [2] Tareen B, Godoy G, Sankin A, et al. Laterality alone should not drive selection of candidates for hemi-ablative focal therapy. J Urol 2009; 181:1082–90. [3] Mouraviev V, Mayes JM, Polascik TJ. Pathologic basis of focal therapy for early-stage prostate cancer. Nat Rev Urol 2009;6:205–15. [4] Eggener S, Salomon G, Scardino PT, et al. Focal Therapy for prostate cancer: Possibilities and limitations. Eur Urol 2010;58:57– 64. [5] Scales CD Jr., Presti JC Jr., Kane CJ, et al. Predicting unilateral prostate cancer based on biopsy features: Implications for focal ablative therapy—results from the SEARCH database. J Urol 2007;178: 1249 –52. [6] Bolenz C, Gierth M, Grobholz R, et al. Clinical staging error in prostate cancer: Localization and relevance of undetected tumor areas. BJU Int 2009;103:1184 –9. [7] Bostwick DG, Waters DJ, Farley ER, et al. Group consensus reports from the Consensus Conference on Focal Treatment of Prostatic Carcinoma, Celebration, Florida, February 24, 2006. Urology 2007; 70(6 Suppl):42– 4. [8] Moreira Leite KR, Camara-Lopes LH, Dall’Oglio MF, et al. Upgrading the Gleason score in extended prostate biopsy: Implications for treatment choice. Int J Radiat Oncol Biol Phys 2009;73:252– 6. [9] Ahyai SA, Isbarn H, Karakiewicz PI, et al. The presence of prostate cancer on saturation biopsy can be accurately predicted. BJU Int 2010;105:636 – 41. [10] Falzarano SM, Zhou M, Hernandez AV, et al. Can saturation biopsy predict prostate cancer localization in radical prostatectomy specimens: A correlative study and implications for focal therapy. J Urol 2010;76:682–7. [11] Kirkham AP, Emberton M, Allen C. How good is MRI at detecting and characterizing cancer within the prostate? Eur Urol 2006;50: 1163–74. [12] Sartor AO, Hricak H, Wheeler TM, et al. Evaluating localized prostate cancer and identifying candidates for focal therapy. J Urol 2008; 72(6 Suppl.):12–24.
Original article
Are we able to correctly identify prostate cancer patients who could be adequately treated by focal therapy? Betina Katz, M.D.a, Miguel Srougi, M.D., Ph.D.b, Marcos Dall’Oglio, M.D., Ph.D.b, Adriano J. Nesrallah, M.D., Ph.D.b, Alexandre C. Sant’Anna, M.D., Ph.D.a, José Pontes Jr., M.D., Ph.D.b, Sabrina T. Reis, M.Sc.b, Adriana Sañudo, Ph.D.b, Luiz H. Camara-Lopes, M.D.a, Katia R.M. Leite, M.D., Ph.D.a,b,* b
a Laboratory of Surgical and Molecular Pathology, Sao Paulo, Brazil Laboratory of Medical Investigation, Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil
Received 26 July 2010; received in revised form 31 August 2010; accepted 29 October 2010
Abstract Introduction and Objective: Because of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer (PC) has been proposed for patients with low-risk disease. Such treatment would allow the control of cancer, thereby diminishing side effects, such as urinary incontinence and sexual dysfunction, which have an enormous impact on quality of life. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy. Our aim is to determine whether there is any preoperative feature that can help select the ideal patient for focal therapy. Material and methods: A total of 599 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy followed by radical prostatectomy to treat PC were examined in our laboratory between 2001 and 2009. We established very restricted criteria to select patients with very-low-risk disease for whom focal therapy would be suitable (only 1 biopsy core positive, tumor no larger than 80% of a single core, no perineural invasion, PSA serum level ⬍ 10 ng/ml, Gleason score ⬍ 7 and clinical stage T1c, T2a– b). We defined 2 groups of patients who would be either adequately treated or not treated by focal therapy. The primary endpoint was the evaluation of preoperative features in order to identify which parameters should be considered when choosing good candidates for focal therapy. Results: Fifty-six out of 599 patients met our criteria. The mean age was 59 years, and the mean number of biopsy cores was 14.4. Forty-seven (83.9%) were staged T1c, and 9 (16.1%) were staged T2a– b. Forty-four (78.6%) patients could be considered to have been adequately treated by focal therapy, and 12 (21.4%) could not. There was no statistical difference between the 2 groups considering age, clinical stage, PSA levels, Gleason score, and tumor volume in the biopsy. All 12 patients who could be considered inadequately treated had a bilateral, significant secondary tumor, 58.3% had Gleason ⱖ 7, and 25% were staged pT3. Conclusion: Although focal therapy might be a good option for patients with localized prostate cancer, we are so far unable to select which of them would benefit from it based on preoperative data, even using very restricted criteria, and a considerable proportion of men would still be left undertreated. © 2012 Elsevier Inc. All rights reserved. Keywords: Focal therapy; Risk stratification multifocal; Index lesion
1. Introduction Because of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer has been proposed for patients with very-low-risk or low-risk disease [1]. Such treatment ranges from precise lesion targeted ablation to subtotal gland treat* Corresponding author. Tel.: ⫹55-11-30617183; fax: ⫹55-11-32312249. E-mail address: [email protected] (K.R. Moreira Leite). 1078-1439/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.urolonc.2010.10.010
ment and has been offered as a means of treating with efficacy prostate cancer diminishing possible damage to the vital structures essential for maintaining normal urinary and sexual function without compromising cancer control [2]. An increasing number of men with low-risk prostate cancer may be overtreated with the conventional whole gland therapy: 11% of those submitted to radical prostatectomy (RP), and 45% received radiation therapy [3]. Even though many of them would have the option of active surveillance, this approach has not gained popularity be-
B. Katz et al. / Urologic Oncology: Seminars and Original Investigations 30 (2012) 794 –797
795
Fig. 1. Classification of patients as either adequately or inadequately treated by focal therapy.
cause observational strategies can lead to significant anxiety [2,4]. It is believed that 20% to 30% of men with low-risk prostate cancer in the U.S. could be candidates for parenchyma-preserving approaches [3]. The main challenge is to preoperatively identify the patients who have real low-grade adenocarcinoma based on the clinical and biopsy data. Nonetheless, the question as to whether these data are sufficiently accurate to decide for a partial ablation of the prostate while guaranteeing cancer curability still remains. The aim of our study is to determine which preoperative features can help select the ideal patients for focal therapy in a highly restricted group of patients regarded as harboring a very-low-risk adenocarcinoma.
was bilateral or there was a clinically significant secondary lesion, characterized by tumor volume ⬎ 0.05 cm3, Gleason score ⬎ 6, positive surgical margins, or extraprostatic extension. The primary endpoint was to determine the preoperative features that could correctly identify which patients should be considered good candidates for focal therapy. Statistical analyses were performed by using SPSS ver. 15.0 (SPSS Inc., Chicago, IL), and for standardization the non-parametric Mann-Whitney test was used for all numeric parameters. The exact Fisher test was used for categorical parameters. Statistical significance was considered when P ⬍ 0.05.
3. Results 2. Materials and methods A total of 599 patients who underwent transrectal ultrasound-guided prostate biopsy followed by RP for prostate cancer were examined in our laboratory from January 2001 to October 2009. All patients were treated by a single surgeon, and all the biopsies and surgical specimens were examined by the same uropathologist. The RP specimens were always examined in toto. Patients with low-risk features for whom focal therapy would be suitable were selected based on the following inclusion criteria: a single biopsy core positive; tumor extent present in less than 80% of a single core; no perineural invasion identified; PSA serum level ⬍ 10 ng/ml; Gleason score ⬍ 7; and clinical stage T1c, T2a, or T2b. In total, 56 patients met the inclusion criteria, and after treatment they were divided into 2 groups (Fig. 1). The first group was defined as adequately treated, which means that the tumor was unilateral and the secondary lesion, if present, was not clinically significant. The other group was defined as inadequately treated; in these patients the tumor
Of 599 men, 56 patients met our criteria. Forty-seven (83.9%) were staged T1c and 9 (16.1%) were staged T2a– b. The clinical and histologic data of all patients are presented in Table 1. Analyzing the radical prostatectomy specimens, 34 (60.7%) adenocarcinomas were bilateral and 30 (53.6%) were multifocal. The mean volume of the index tumor was 1.8 cm3, median 1.4 cm3, ranging from 0.3 to 8.3 cm3. Only 1 patient had an insignificant index tumor. The secondary,
Table 1 Clinical and histopathologic data of patients that could be eligible for focal therapy
Mean Median Minimum Maximum
Age (years)
N of cores
Gleason score
Greatest % of a single core
Total % of tumor
59 59 39 76
14.4 14 6 28
5.8 6 4 6
23.2 20 5 70
1.9 1.4 0.4 12
796
B. Katz et al. / Urologic Oncology: Seminars and Original Investigations 30 (2012) 794 –797
smaller tumors ranged from 0.1 to 4.9 cm3, median 0.4 cm3 and mean 0.84 cm3. Twelve (21.4%) index tumors were present at the contralateral lobe considering the biopsy result, 3 of them containing Gleason pattern 4. Twenty-two (39.2%) patients had the Gleason score increased from ⱕ6 to ⱖ7. Only 4 patients had extraprostatic extension, and only 3 patients had positive margins. Of the 56 patients, 44 (78.6%) could be adequately treated, meaning that the biopsy results localized the correct lobe affected by the index tumor. Another factor we considered a positive correlation was the detection of an insignificant secondary tumor (⬍0.5 cm3, Gleason ⬍7, organconfined) at the RP. Twelve (21.4%) patients would not have been adequately treated with focal therapy because the tumor was bilateral and/or the secondary tumor could not be considered insignificant. Seven (58.3%) had Gleason 7 or 8, and 3 (25%) were staged pT3a. The patients were distributed as follows: 5 (41.7%) had secondary tumor with Gleason score 7 and significant tumor volume (⬎0.5 cm3); 3 (25.0%) had Gleason score 7 or 8, significant tumor volume and were staged pT3, and 4 (33.3%) had tumor larger than 0.5 cm3. After analyzing whether any preoperative feature would help us to determine the patient’s suitability for focal therapy, neither clinical nor histologic characteristics were able to identify the correct group of tumors (Table 2).
4. Discussion By selecting a very restricted group of patients and considering only the most favorable preoperative data, we were able to show that 78.6% of patients would be treated appropriately by focal therapy, which means that an isolated or an index significant tumor would be ablated. Curiously, no preoperative data were able to identify the 21.4% of patients with significant contralateral adenocarcinomas. Table 2 Clinical and histopathologic data of patients that could or could not be treated adequately with focal therapy Treatment
Age (mean) Clinical stage T1 T2 PSA (ng/ml) Gleason score 4 5 6 Total % of tumor (mean) Greatest % of tumor in a single core (mean)
P
Inadequate 12 (21.4%)
Adequate 44 (78.6%)
61.7
58.2
10 (83.3%) 2 (16.7%) 6.6
37 (84.1%) 7 (15.9%) 5.1
⬎0.999 0.355
0 3 (25%) 9 (75%) 2 25.8
1 (2.3%) 5 (11.4%) 38 (86.4%) 1.8 22.5
0.491 0.494 0.457
0.317
Other researchers have also tried to determine whether it is possible to identify the ideal candidates for preservative therapies, but the preoperative aspects were not as restrictive as ours [1,2]. The strong point of our study is the high restraining clinical and histopathologic criteria that could indicate the ideal candidate for the focal treatment. Similar to our findings, Scales et al. [5] described patients with low-risk prostate cancer (stage T1c or T2a, PSA levels ⬍ 10, Gleason ⱕ 6, 1 or 2 ipsilateral positive cores), showing that only 35.1% had unilateral disease in RP specimens and that no clinical or pathologic feature was related to pathologically unilateral or bilateral disease on the multivariate analysis. In contrast to our data, Bolenz et al. [6] found that higher PSA levels, higher clinical stage, and a higher Gleason score at biopsy were independent predictors of tumor upgrading. In their series, 40.3% of tumors involved the prostatic capsule on the negative biopsy side. But in their study, the only criterion for selection of the patients was the occurrence of a unilateral tumor at the biopsy; almost one-third of the biopsies scored Gleason 7 or higher. Some authors argue that focal treatment is inadequate for a multifocal and heterogeneous tumor such as prostate cancer. Multifocal prostate cancer is present in up to 87% of RP specimens [7], and the efficacy of biopsy in identifying laterality still remains poor. In addition, only 15% to 35% of men with unilateral disease on biopsy have unilateral cancer in the RP specimen [5]. However, about 80% of non-index tumors could be considered insignificant, with small volume (ⱕ0.5 cm) and without the most aggressive Gleason pattern (Gleason 4 or 5), suggesting that the index tumor is the main determinant of prognosis and that focal therapy would eradicate the known cancer focus with the highest likelihood of progression [2,7]. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy to recommend subtotal therapy. Only a few studies determined the correlation between prostate biopsy findings and pathologic outcome after RP. Prostate biopsy accounts for significant undergrading in up to one-third of all patients [8], and an initial transrectal ultrasound (TRUS) biopsy might miss tumor areas in up to 30% of patients. The most frequent location of undetected cancer is in the dorsolateral region, anterior, and the apex of the prostate, which are not always represented in current biopsy strategies [6]. The number of cores needed to adequately sample the prostate is unknown and has been related to the size of the gland. In our study, the mean and median number of cores was 14.4 and 14, respectively, with a number higher than the 10 to 12 recommended for prostate cancer diagnosis. Some authors have proposed using extended prostate biopsy strategies to help increase cancer detection and the identification of tumors with unfavorable characteristics that would impose a more aggressive treatment [9]. Falzarano et al. found that all bilateral tumors detected by extended biopsy were confirmed to be bilateral in the RP, but only
B. Katz et al. / Urologic Oncology: Seminars and Original Investigations 30 (2012) 794 –797
10% of the patients with unilateral adenocarcinomas had unilateral cancer. However, most missed tumor foci (76%) were clinically insignificant [10]. Therefore, a negative extended biopsy does not confirm the absence of cancer in the corresponding side of the gland and cannot be used as a single determinant when considering a patient for focal treatment. Modern imaging technology, especially MRI and magnetic resonance spectroscopic imaging, could help in directing the needle toward areas of suspected cancer involvement [11]. Also, imaging before treatment could determine the tumor’s location as well as its volume and could exclude a more extensive cancer [12]. MRI of the prostate using novel techniques such as dynamic contrast enhancement and diffusion-weighted imaging are increasingly being used to stage primary prostate cancer, with excellent results. The evaluation of outcome and follow-up of patients submitted to focal therapy is still unknown, and there is no data on long-term outcomes such as functional status, oncologic efficacy, and the impact on subsequent therapy. If patients with true unilateral disease have better outcome, whole gland treatment could be avoided in these patients. The difficulty still lies in identifying which men could benefit from a less aggressive modality of treatment without compromising cancer curability.
5. Conclusion Even though focal therapy might be a good option for patients with localized prostate cancer, as of now there is no data that could adequately select which of them would benefit from it based on preoperative data, even being extremely restricted in the selection of patients. Characteristics such as age, clinical stage, PSA levels, percentage of the tumor in a single core, and total percentage of the tumor in
797
the biopsy did not add any further information about the ideal patient for focal therapy.
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