Year XVII n. 4/01

As life expectancy increases, symptoms caused by prostatic pathologies are getting to be more and more a socially relevant problem, since it is well-known that they affect a growing number of males over 50 years of age.

Suffice it to think that in Italy, the percentage of men under 50 affected by adenomatous hyperplasia (benign prostatic hypertrophy - BPH) is approximately 15%, while it rises to 50% in the 50-to-60 age range, and is more than 80% in men over 80; a similar trend is found, albeit with obviously much lower percentages, in prostate cancer, which is man’s most common cancer in the western world. We must moreover remember also inflammatory pathologies of the prostatic gland which affect also – and mostly - young males aged between 20 and 40 years, and cause disturbances not only to micturition but also to erection and fertility.

The increase of prostatic pathologies has naturally lead to a growing increase of interest in these diseases, that has brought extraordinary progress in scientific achievements, from both a diagnostic and a therapeutic point of view.

Step by step diagnostic procedure First step of the diagnostic procedure is to make general practitioners fully aware of the importance of early diagnosis of this type of diseases, bearing in mind that if BPH and prostatitis may give early symptoms, prostatic cancer causes symptoms only at a very advanced stage. Therefore, even if there are no symptoms, it is important that men over 50 have a check-up done by a urologist, who will be able to determine size and consistency of the prostate by means of a rectal examination.

The next step is to determine PSA values (prostate-specific antigene); should the rectal examination be negative and PSA values within a limit of 4 ng/ml, an asymptomatic patient might be reasonably told to return for another checkup after one year.

If PSA values are normal, and the examination suggests an enlargement of the prostate, an abdominal ultrasound is indicated (Fig. 1) in order to evaluate the urinary system, besides a baseline urodynamic study which, by means of a urinary flow study (Fig. 2), will allow us to evaluate any degree of obstruction caused by prostatic hypertrophy.

If PSA values are elevated, with values ranging from 4 to 10 ng/ml, the ratio between FREE PSA and TOTAL PSA , must be controlled: if values are under 15% , the elevation of PSA is most probably due to a neoplastic process, while if the ratio is over 15%, the altered PSA value might be caused by hypertrophy of the prostate.

In case the PSA values are over 10 ng/ml it will not be necessary to check the free-to-total PSA ratio, since the PSA value by itself is suggestive of neoplastic degeneration.

So, should the PSA present an altered value, or the rectal examination have detected any suspect area, the next diagnostic “step” will be to perform a “Transrectal ultrasound image of the prostate” (Fig. 3) which is more invasive than the abdominal examination but allows for a much more scrupulous and accurate morphologic evaluation.

It has recently become possible to associate the ultrasound examination with a Color-Doppler study of the prostate (fig. 4), which allows to evaluate any hypervascularization of the echographically suspect areas.

If at this point the transrectal ultrasound has confirmed the suggestion of neoplasm or if the PSA value is higher than 10 ng/ml, a prostate biopsy under echo guidance ought to be performed (Fig. 5), specifically aimed at echographically evident lesions, or “random” if no suspect areas are evident at ultrasound imaging.

If positive for neoplasia, the analysis of the samples of prostatic tissue will allow us to determine the degree of anaplasia of the tumor, according to a scale from 2 to 10 (Gleason score), the higher the Gleason score is, greater is the degree of malignancy.

If, on the other hand, no tumor is found, it will in any case be possible to check for any precancerous abnormalities in the intraepithelial cells (PIN), should any be found, it will be possible to foresee the future development of the neoplasia: a “low grade” PIN is considered to be uncertain for future malignancy, while a “high grade” PIN is more and more considered to be almost on a par with a hystologically confirmed malignancy.

To date, the debate as to the opportunity of running yearly mass screening checkups of all men over 50 is ongoing in Italy and elsewhere; recently, in the United States it became once again a popular topic when the US Postal Service issued stamps on this theme, thus giving rise to controversies between pro and con groups.

It is easy to foresee that a mass “screening” for prostatic pathologies, besides having elevated social costs, might also lead to phenomena of “overtreatment” of tumors which are at times so slow in developing that they would not cause in any case the death of the patient, or might give rise to diagnostic uncertainty (such as in the case of continuously elevated PSA values, with no clinical or echographic evidence of suspect prostatic areas, and negative biopsies) thus being very stressful and distressing for the patient; on the other hand we feel that the possibility of reaching an early diagnosis of cancer and thus giving the patient therapeutic options which may lead to full recovery is so important that we advocate the opportunity of performing similar controls.

Therapy Once BPH has been diagnosed, decisions have to made as to the therapy.

Before analyzing all the various therapeutic possibilities, we ought to stop and consider the etiopathogenetic mechanisms of prostatic hypertrophy. The many clinical symptoms caused by the enlargement of the prostate are the result of the related urinary flow obstruction.

Such obstruction has both a static and a dynamic component: the static component is caused by the compression exerted on the easily depressible walls of the intraprostatic urethra by the enlarged adenoma as it grows in size; the dynamic component instead refers to an alpha-1-adrenergic-mediated hypertonia of the smooth muscles of bladder neck, intraprostatic urethra and prostatic stroma.

Thus pharmacological studies have aimed at reducing the size of the gland or at decreasing the tension of the smooth muscles of the prostate. Among the medications which act by reducing size of the prostate, besides the well-known vegetable extract and mepartricin preparations and the estrogens and antiandrogens which are rather difficult to manage, there currently is finasteride: this molecule is an competitive inhibitor of 5-alpha-reductase, which is an enzyme essential to the transformation of testosterone into di-hydrotestosterone; since di-hydrotestosterone is the main hormone involved in prostatic growth, the use of finasteride may block the enlargement of the prostate and reduce its size up to 20%.

Therefore it is indicated for patients who, when diagnosed, present a moderately enlarged prostate; it must be said however that this medication is not very easy to use since it has a rather long latency period (it starts giving results after at least 3 months of administration), it has significant side effects for those patients who are still sexually active (decrease of libido and of erectile capability) and finally artificially masks the elevation of PSA values (so that it should not be used in cases where there is a suggestion of cancer in association with hypertrophy).

Among medications that are active by decreasing muscle hypertonia there currently is the class of alpha-1-litics, which by blocking the alpha-1-adrenergic receptors act by relaxing the vesico-cervico-prostatic smooth musculature, thus reducing resistance to urinary flow and consequently improving symptoms caused by the dynamic component of the obstruction.

The side effects which cause more discomfort are related to hypotensive episodes (alpha-lytics are antihypertensive drugs), have been gradually solved by pharmacological research, after identifying molecules which are selectively active on a subgroup of adrenergic receptors, alpha-1A receptors, which are present almost exclusively at the level of the bladder neck and the prostate and absent at the level of the large blood vessels. Therefore these superselective drugs may be prescribed with the utmost confidence and are indicated for those conditions where obstructive symptoms seem to be mostly related to the dynamic component (moderate enlargement of the prostate). Although medical therapy can be effective, there still remains a certain percentage of patients for whom this approach does not solve obstructive symptoms adequately or for a long enough period; this is the reason why also surgical techniques have, in the past few years, been greatly improved from a quality point of view, so that nowadays in the United States an endoscopic disobstructive procedure, the transurethral resection of the prostatic adenoma (TURP), is the most common therapeutic approach for BPH and is the second most frequent operation on males (drawing no. 1).

The possibility of carrying out these procedures no longer having to look directly through the endoscopic resector optic but more comfortably by looking at a monitor connected to the instrument, and which is by now routinely done at more and more urology centres, has allowed to improve not only procedure time, therefore extending indication of the procedure also to prostates larger than 80 cc, but making this technique easier to learn, so that it no longer is the prerogative of a single surgeon. All this has made TURP a very safe operation, although it has not eliminated all complications (hemorrhages, incontinence, infections, impotence) and mortality, which, however, is very low (< 1%). Moreover, in about 10% of all cases, the procedure is not completely decisive so that the patient must resort to another surgical procedure within 10 years of the first TURP.

An alternative to endoscopic procedures which is becoming less commonly used is the “open surgery” Prostatic adenectomy, which can be performed either by tranvesical or retropubic route and is used only for cases where the adenoma is greatly enlarged, since it is of greater magnitude, with risks of heavier bleeding and with longer periods of hospitalisation as compared to endoscopic procedures.

Laser (TULIP) may be used on patients for whom anesthesia is not recommended for any reason, in order to obtain an at least partial endoscopic disobstruction performed with local anesthesia and practically no perioperative bleeding. If instead the obstruction depends on the bladder neck being rigid or on the prostate being small and fibrous, then it will be possible to perform several endoscopic incisions (TUIP), since by removing no tissue, being an extremely quick operation and entailing no risks of hemorrhages it will allow for micturition to be restored easily and without hindrance.

We will give our opinion concerning the new techniques presented during the 1999 conference of the Society of American Urologists, such as the possibility of “deflating” the prostate by means of injections of denaturated alcohol, a quick procedure which is performed on an outpatient basis, with local anesthesia, only after more details and data are made available, although experience has taught us to be sceptical about these innovations which so often seem to disappear just as fast as they have appeared.

If instead at the end of the diagnostic procedure we unfortunately get a diagnosis of prostatic neoplasm, most appropriate therapy will have to be determined. Association of PSA values with Gleason score gives us a nomogram which allows to evaluate in percentage the likelihood of the cancer spreading beyond the prostate and will therefore be a crucial factor in deciding on the therapeutic approach. Should staging demonstrate the disease is still localized to the prostatic gland, the first choice therapy will be radical surgery with complete removal of the prostate.

This procedure, which until just a few years ago was performed by retropubic access, through an abdominal incision, and was considered to be among the so-called “major” operations, i.e. a serious surgical procedure, entailing great intraoperative bleeding, elevated risk of embolies, with a long and complex period of hospitalisation and post-operative recovery, in the past few years has been greatly improved with reduction of bleeding, embolic complications and postoperative hospitalisation thanks to possibility of reaching the prostate by means of a perineal incision (between testes and anus), and is therefore now quite rightly considered to be one of the so-called “mini-invasive” surgical procedures.

The diffusion of the perineal approach to radical prostatectomy in the United States has greatly contributed to its success, along with the new opportunities of patient follow-up in the following months and years, with diagnostic instruments that allow us an early detection of a possible recurrence of cancer.

Our group at San Giuseppe Hospital has perfected and standardized a perineal procedure for radical Prostatectomy which differs slightly from the classic version used in the United States by Paulson and Weldon but that has managed to optimise the operation by reducing complications to a minimum and by turning the perineal procedure from a “major” operation which presented risks of infection due to contact with feces, into a “minor”, intraoperatively aseptical, “clean” operation, with a close to zero bleeding risk. For this reason, since it no longer entails an elevated cost/benefit ratio, we are able to “routinely” use this procedure in clinical T2 cases, with PSA < 29 and a Gleason score of <7, where we can reasonably assume the tumor to be strictly localized to the prostate.

In selected cases it can be used also for clinical T2 cases that present higher PSA values, with a view to perform debulking surgery, i.e., a reduction of the organic neoplastic mass to ensure a better quality of life in case of progression of the disease and in order to eliminate all the bladder and rectal symptoms such as retention, urgency, pollukiuria and dysuria. It has recently become possible to evaluate even minimal alterations of PSA values (Ultrasensitive PSA) so that it is no longer necessary to remove pelvic lymph nodes together with the prostate for a positive staging of disease, in order to initiate postoperative hormonal chemotherapy should the examination of the removed lymph nodes prove that the tumor has extended beyond the prostate. It is more and more widely believed that the decision to start hormonal chemotherapy after surgery may be taken on the basis of an elevation of PSA values, which after radical prostatectomy drop to zero (biochemical recurrence).

When diagnostic examinations show instead a condition of neoplasia extending beyond the prostate, it is evident that the surgical operation no longer has an intent to cure but being so little invasive at the perineal access, can be used anyway, naturally in association with medical therapy in order to remove the main cause of disease (debulking) and to eliminate all symptoms deriving from the difficult micturition caused by the enlarged prostate. Also in this field, in the past few years, there has been an evolution of the classic theories on LHRH-antagonist hormonotherapy, possibly in association with antiandrogens that have for a long time crystallized the therapeutic approach to locally advanced or metastized prostatic cancer. Having determined beyond a doubt that prostatic cancer cells progressively become refractory to hormonal therapy, many researchers are now evaluating other therapeutic options, with studies assessing efficacy of combinations of drugs, often integrated by radiotherapy or by disobstructive surgery; the first results are encouraging.

Urinary incontinence is the most feared amongst post-operative complications that require rehabilitation.

A preoperative urodynamic study will permit to select those patients who, either due to bladder pathology (detrusor instability) or urethral pathology (neurogenic or myogenic impairment of the sphinterical system) present an elevated risk for developing incontinence.

A period of about two months post-surgery is usually to be allowed to solve sphinterical incontinence, which is the physiopathologic root of the problem; in case of incomplete recovery, one or two cycles of rehabilitation of the perineal plane and biofeedback ought to be sufficient to solve the problem.

In cases where after one year post-surgery incomplete incontinence still persists (2-4%), it will be necessary to proceed to surgical correction with the insertion of an artificial sphinterical prosthesis. Another complication which might occur is urethral stenosis at the level of the anastomosis to the bladder (2%), and which almost always can be solved by endoscopic urethrotomy. Intra-operative bleedings are usually mild (approximately 100-200 cc).

Postoperative impotence requires a complex analysis, since maintaining sexual function is more and more of a primary consideration, even though prostate cancer is such a clinically severe pathology. On one hand more attention has been given to sexuality-related issues, on the other the diffusion of early screenings have brought a greater number of patients to be operated on at a younger age than what was usual in the past and therefore at an age when maintaining sexual function is considered of paramount importance.

Erectile deficits which follow a radical prostatectomy are related to the autonomic innervation of the cavernous bodies while the pudendal nerve is not involved: these patients in fact present penile sensibility on the surface and can climax without attaining rigidity.

Other factors that affect erectile capability are age, quality of prior erectile function and preoperative hormonotherapy when administered: the most damaging factor is hormonal therapy, as compared to surgery, since no remedies are effective for cases where there has been a total loss of libido, while effective remedies are available for cases with preserved libido.

Localized diffusion of the tumor is, in our opinion, not as important, since we focus our attention on oncologic radicality rather than on the postoperative erectile deficit which is easily curable, also since we do not believe that nerve-sparing techniques are entirely effective, so that we aim at an early erectile rehabilitation after surgery.

That having been said, we must now remember that two therapeutic options are available: pharmacotherapy, either systemic with Sildenafil or intracavernous with PGE1 and the possible implantation of a penile prosthesis: it is important to stress that in the case of pharmacological treatment, therapy should be initiated early, that it has rehabilitative intents and that it is advisable to proceed starting from Day 10-15 post surgery.

The early recovery of erectile functions aims at blocking the metabolic-histal mechanism that leads to a chronic fibrosis-anoxia which is at the bottom of the post-operative venocclusive erectile pathology. In fact nowadays the spontaneous, nocturnal erections are considered to be a phyisiologic mechanism of defence against cavernous fibrotic involution.

Hence the importance of an early administration of pharmaco-infusive therapy or of Sildenafil; the latter, increasing the cavernous capacity of the final chemical mediator at erection, might help the erection itself even if a iatrogenic neurologic lesion reduces impulse conduction. Postoperative checkups, in the case of surgery for BPH, will just control the recovery of urinary flow, performing a urine flow study about 3 months after surgery and a yearly specialist checkup after having PSA values tested; neoplasm might develop in the residual prostatic tissue (capsule).

Follow-up of radical prostatectomy patients is quite a different consideration, since like for all neoplastic patients it is necessary to perform accurate, frequent checkups over a long period of time.

Regardless of the result of histology, all patients operated on at our Division have their PSA tested by Ultrasensitive PSA method (a technique which practically rules out any chance of analizing device errors in very low PSA values, ranging from 0.003 and 0.01) monthly for the first 6 months and afterwards, should values found to be consistently zero, every 3 months for the next 5 years; moreover, they will undergo a transrectal ultrasound every 6 months and a total body bone scintigraphy yearly, for 5 years.

Finally, treatment is completely different when the prostatic pathology is an inflammation (prostatitis), as it often recurring and chronic. This pathology typically affects younger males, aged between 20 and 40 and causes irritative sympatoms rather than obstructive ones.

Only elderly in patients, when an acute inflammatory condition (prostatic adenomitis) is associated with a condition of primary BPH, symptoms might be those of an acute obstruction (urinary retention) due to the congestive enlargement of the already hypertrophic prostate. Generally speaking, prostatic inflammations can be bacterial or congestive. Bacterial inflammations may derive from urethral infections that reach the prostate travelling up the urethral canal (prostatitis caused by urethritis) and often are the consequence of infections contracted during intercourse (drawing no. 2).

They must be treated vigorously with antibiotic therapy.

More frequently, the bacteria which contaminate the prostate do not originate from the urethral canal, but descend through the lymphatic system or by proximity to the bowel (drawing no. 3). In these cases an appropriate therapy aims at re-establishing the normal bacterial flora of the intestine besides fighting the pathogenic germs which have reached the prostate. Diet, control of the neurovegetative system and of the intestine bacterial flora are the main therapeutical actions in the treatment of the very frequent Congestive Prostatitis, which is the expression of a pelvic vascular congestion, characterized by a congestive inflammation of the prostate and at times by the growth of hemorrhoids. In these cases, excessive sexual activity might be a concomitant factor causing congestion.

Among therapeutic means available nowadays, besides the classical prostatic massage (to void the congested gland) there are also ultrasound or laser endorectal probes, which have a decongestant effect on the prostatic parenchyma and that may successfully integrate the other therapeutic options.

(traduzione dell’Autore)

Edoardo Austoni

Cattedra di Urologia Clinica Urologica

Università di Milano

DIS. 1 In nero è raffigurata la parte adenomatosa della prostata che nell’IPB provoca i fenomeni ostruttivi. Nel disegno a destra, il risultato della disostruzione chirurgica.

The adenomatous area of the prostate, which causes BPH obstructive symptoms is shown in black. The figure to the right shows the result of surgical disobstruction

DIS. 2 Patogenesi “ascendente” delle infezioni prostatiche.

“Ascending” pathogenesis of prostatic infections

DIS. 3 Patogenesi “discendente” delle infezioni prostatiche.

“Descending” pathogenesis of prostatic infections

FIG. 1 Ecografia addominale: scansione longitudinale di grosso lobo medio prostatico che aggetta in vescica.

Abdominal ultrasound: longitudinal scansion of a large prostatic middle lobe which protrudes into the bladder.

FIG. 2 Tracciato uroflussimetrico: nel tracciato inferiore la pressione minzionale è ridotta mentre il tempo di svuotamento è allungato.

Urine flow study tracing: in the lower tracing micturition pressure is reduced while the voiding time is longer.

FIG. 3 Ecografia transrettale: area ipoecogena paramediana sinistra.

Transrectal ultrasound: hypoechogenic area in the left paramedian region

FIG. 4 Ecocolordoppler della prostata: segni di ipervascolarizzazione a livello di nodulo iperecogeno.

Echo-color-Doppler imaging of the prostate: evidence of hypervascularization at the level of a hyperechogenic nodule.

FIG. 5 Agobiopsia prostatica ecoguidata: in alto a destra si vede il segnale dell’ago che sta entrando nel tessuto prostatico.

Needle biopsy of the prostate under echographic guidance: the signal of the needle entering the prostatic tissue is visible at the right upper hand

FIG. 6 Posizione del malato durante la prostatectomia perineale.

Position of the patient for a perineal prostatectomy

FIG. 7 Un telino sterile viene suturato al labbro inferiore dell’incisione chirurgica per garantire un completo isolamento del campo operatorio dal retto.

A small sterile drape is sewn to the lower edge of the surgical incision in order to ensure complete isolation of rectal surgical field.

FIG. 8 Incisione chirurgica.

Surgical incision

FIG. 9 Enucleazione in blocco della prostata, delle vescicole seminali e dei monconi dei dotti deferenti.

Complete removal of prostate, seminal vesicles and the stumps of the vasa deferens.

FIG. 10 Sutura cutanea al termine dell’intervento

Suture of the skin at the end of the procedure

FIG. 11 Pezzo operatorio.

Surgical specimen