9. Aftercare – Prostate Cancer

Background information

Re: Recommendation 9.1

Follow-up is an integral part of medical care in the treatment context: meeting the patient's need for discussion, educating and guiding the patient on the one hand, and detecting recurrence at a treatable stage on the other.

In this context, the PSA value has an outstanding significance for treatment monitoring. After local therapy, a baseline value should be established within six to twelve weeks in order to draw further therapeutic consequences, e.g., from a lack of PSA drop after radical prostatectomy.

Re: Recommendation 9.2

The diagnosis of a recurrence is primarily based on the detection of a PSA rise, i.e. biochemically. A PSA rise after radical prostatectomy or curatively intended radiotherapy may be due to either local recurrence or metastases. The localization of the recurrence is of crucial importance only if local recurrence therapy is an option for the patient. If this is ruled out because of a high risk of complications, serious concomitant diseases, or the patient's refusal to undergo this measure, no diagnosis is necessary because of the lack of consequence. In the further course of the disease, examinations should be symptom-oriented.

Re: Recommendation 9.3

A DRE is useful in the detection and staging of prostate cancer. In contrast, the method is superfluous in follow-up after radical prostatectomy and radical radiotherapy (percutaneous and/or brachytherapy), since recurrence is indicated much earlier and more reliably by PSA rise than by DRE. Therefore, regular PSA checks should be performed to exclude recurrences. Regular DRE should be limited to patients with tumors that do not secrete PSA [1024].

Re: Recommendation 9.4

In the case of biochemical recurrence, various imaging techniques with different sensitivity and specificity can be used to confirm local recurrence. Conventional methods such as CT and TRUS are rarely able to localize recurrences with sufficient diagnostic accuracy. MRI (especially with endorectal coil) is more informative, supplemented by magnetic resonance spectroscopy, as it can excellently visualize extracapsular tumor spread and seminal vesicle infiltration. It therefore seems to be the method of choice in the diagnosis of recurrence [222]. For planning salvage therapy, according to various publications, dynamic contrast-enhanced MRI is better in detecting and localizing the recurrence in the peripheral zone after percutaneous irradiation compared to T2 weighting [1025].

Recurrence therapy is more successful the lower the rising PSA level. Since the informative value of all imaging techniques is dependent on tumor size, this is limited in the case of relatively low PSA values or early recurrences (see also Chapter Staging).

Background information

Re: Recommendation 9.5

The symptoms of testosterone deficiency are well known in the context of the various diseases of the hypogonadism group. Urologists are also familiar with the effects of testosterone deficiency as an iatrogenic condition in the context of androgen deprivation therapy for the treatment of PCa. Thus, testosterone levels achieved in the castration range in the context of GnRH agonist therapy have been found to lead to severe osteoporosis and increased fracture risk [1029], as well as an increased incidence of diabetes and cardiovascular disease [1030], and increased mortality from myocardial infarction [D'Amico, A.V. et al. 2007]. In a review paper, Pinthus et al. [1032] concluded: "Cardiovascular disease is the most common cause of death in men with prostate cancer, more often than the malignancy itself". Epidemiological studies of patients with Klinefelter syndrome, who usually have testosterone deficiency from the beginning of the third decade of life, show an increased general morbidity and mortality of these men compared to the normal population [1033], [1034].

These objectifiable findings and the suffering of the many patients suffering from testosterone deficiency who are treated for prostate cancer raise the question of whether PCa patients can be substituted with testosterone after successful cancer treatment with curative intent.

Against this background, therapists have started treatment with testosterone in individual cases after successful therapy of a PCa (e.g. by castration) and an adequate recurrence-free interval. Three published case series are available on this topic: Kaufman and Graydon [1028] report seven hypogonadal patients after curative radical prostatectomy who did not have recurrence of PCa with testosterone therapy. Agarwal and Oefelein [1027] describe ten more such patients, and Sarosdy [1026] reports 31 PCa patients treated with testosterone 4.5 (0.5-8.5) years after brachytherapy without recurrence. It is not reported for how long testosterone substitution was used. However, the case series described cannot provide evidence that testosterone substitution after curative therapy is harmless, both because of their number of cases and the lack of a control group.

The authors of this guideline see the need for a statement on testosterone substitution in clinically severely symptomatic patients with proven testosterone deficiency after curative therapy for prostate cancer. Since testosterone substitution may provide a reduction in symptoms and risks of testosterone deficiency for these patients and also a substantial increase in quality of life, its use in this patient population should not be categorically excluded. However, due to the insufficient evidence regarding the occurrence of recurrences during therapy and in the absence of approval of testosterone in patients with PCa, special attention should be paid to detailed education and close monitoring.

Re: Recommendation 9.6 and 9.7

In order to assess a response to hormone deprivation, regular monitoring is required. The history and examination serve both to evaluate the clinical findings and to diagnose possible side effects of hormone-ablation therapy (for ADRs of hormone-ablative therapy and their treatment, see Table 19 in the chapter on supportive and palliative treatment). Side effects can thus be detected and treated at an early stage.

A three-month examination interval has proven effective; this can also be changed on an individual basis. The determination of the PSA baseline is important for further monitoring [190], [746].

In any case, it is important to assess the current medical history in order to determine new symptoms or changes in existing symptoms (e.g. bone pain). In addition, elicitation of physical status (e.g., skin coloration, weight changes) is necessary.

A digital-rectal examination may be useful in locally advanced prostate cancer. Otherwise, a digital-rectal examination is not always necessary in patients undergoing hormone ablation therapy, but should be performed on a symptom-oriented basis. In any case, it is necessary to check the PSA value in order to monitor the response to hormone ablation therapy and the further effectiveness of this measure. In addition, a determination of the serum testosterone value may be necessary in case of non-response.

In stable disease after verified effective initiation of hormone ablation therapy, the frequency of check-ups may also be reduced, especially in the early phase of this disease phase, but should be performed at least twice a year. Other laboratory tests routinely performed during follow-up have no proven diagnostic or therapeutically relevant effect [190], [1035].

During follow-up with hormone ablation therapy, if the PSA response is not satisfactory, testosterone levels should be determined to verify that a castration level has been reached.

In palliative use of systemic therapy, additional laboratory parameters may provide information about:

• Anemia (hemoglobin determination);
• Bone marrow reserve, especially in case of hormone resistance (platelets and leukocytes);
• Renal dysfunction (creatinine and urea);
• Hypercalcemia (serum calcium), especially in the presence of bone metastases.

 

Re: Recommendation 9.8

Imaging (such as bone scintigraphy, CT, MRI, X-ray) should not be used routinely, as patients should be spared unnecessary examinations. The indication for the use of imaging should be made specifically and with a concrete question in mind, and should only be used if therapeutic consequences are to be expected. The use of imaging for mere follow-up is not appropriate at this stage of the disease. Indications for imaging are changes in the clinical condition (symptom increase, change in general condition) and/or new symptoms that may require further treatment (e.g., severe, localized bone pain).